Wednesday, November 30, 2005

Diet and nutrition factors in myeloma?

OBJECTIVES: To explore whether dietary factors contribute to the risk of multiple myeloma and the two-fold higher incidence among blacks compared to whites in the United States. METHODS: Data from a food-frequency questionnaire were analyzed for 346 white and 193 black subjects with multiple myeloma, and 1086 white and 903 black controls who participated in a population-based case-control study of multiple myeloma in three areas of the United States. RESULTS: Elevated risks were associated with obese vs. normal weight (OR = 1.9, 95% confidence interval (CI) = 1.2-3.1 for whites and OR = 1.5, 95% CI = 0.9-2.4 for blacks), while the frequency of obesity was greater for black than white controls. Reduced risks were related to frequent intake of cruciferous vegetables (OR = 0.7, 95% CI = 0.6-0.99) and fish (OR = 0.7, 95% CI = 0.5-0.9) in both races combined, and to vitamin C supplements in whites (OR = 0.6, 95% CI = 0.5-0.9) and blacks (OR = 0.8, 95% CI = 0.5-1.4), with the frequency of vitamin supplement use being greater for white than black controls. However, frequent intake of vitamin C from food and supplements combined was associated with a protective effect in whites (OR = 0.6, 95% CI = 0.4-0.9), but not blacks (OR = 1.2, 95% CI = 0.8-2.1). CONCLUSIONS: The greater use of vitamin C supplements by whites and the higher frequency of obesity among blacks may explain part of the higher incidence of multiple myeloma among blacks compared to whites in the United States. In addition, the increasing prevalence of obesity may have contributed to the upward trend in the incidence of multiple myeloma during recent decades.

Brown LM, Gridley G, Pottern LM, Baris D, Swanso CA, Silverman DT, Hayes RB, Greenberg RS, Swanson GM, Schoenberg JB, Schwartz AG, Fraumeni JF Jr.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health,
Bethesda, MD 20892-7244, USA.

Cancer Causes Control. 2001 Feb;12(2):117-25.
PMID: 11246840 [PubMed - indexed for MEDLINE]

Antiprimod presentation at ASH

Callisto Pharmaceuticals, Inc. KAL (FWB:CA4), announced that its anti-cancer drug candidate Atiprimod has been selected for a second Oral presentation of research data at the annual meeting of American Society of Hematology (ASH).

Callisto's research collaborators at Dana-Farber Cancer Institute will present findings of an animal-based study to investigate the effect of Atiprimod on multiple myeloma tumors, a serious, currently incurable form of blood cancer. The animal study, conducted by researchers at Dana-Farber, observed that Atiprimod produced experimentally significant reduction in tumor levels.

The newly-announced abstract, #249, describes Atiprimod's activity in three mouse models of human multiple myeloma in addition to gene expression profiling data observed on cells exposed to Atiprimod. One of the animal models evaluated the effect of Atiprimod on human multiple myeloma cells in a human bone marrow microenvironment. In this model, mice were implanted with a human fetal bone chip engrafted with multiple myeloma cells and treated i.p. with Atiprimod (40 mg/kg) or vehicle alone (PBS) for two weeks. The researchers observed a 60% reduction in the indicator of anti-tumor activity in mice treated with Atiprimod versus control group. To evaluate effects of Atiprimod on primary patient cells in a human microenvironment, mice were engrafted with patient multiple myeloma cells (IgG gamma) and treated i.p. with Atiprimod (50 mg/kg) or vehicle alone (PBS) for 4 weeks. Treatment with Atiprimod induced a reduction in both human IgG and gamma light chain levels in mouse sera, whereas levels of both proteins continued to rise in mice treated with vehicle alone. The molecular changes in multiple myeloma cells induced by Atiprimod were also evaluated using gene expression profiling of multiple myeloma cells exposed to Atiprimod. Atiprimod induced significant down-regulation of genes involved in growth and cell-cycle control, adhesion, cell-signalling pathways, up-regulation of genes implicated in apoptotic cascades and in negative regulation of signal transduction.

Source: www.callistopharma.com

Tuesday, November 29, 2005

Seattle Genetics targets third disease with SGN-40

Seattle Genetics Inc. (NASDAQ: SGEN - News) announced it is targeting a third condition with its SGN-40 cancer treatment. It has reported early clinical trials of SGN-40 for chronic lymphocytic leukemia (CLL).

The FDA has granted an orphan drug designation for treatment for CLL. SGN-40 previously received orphan drug designation for multiple myeloma. In December 2004, the company began clinical trials of SGN-40 on patients with non-Hodgkin's lymphoma.

For more info on SGN-40
http://myelomic.blogspot.com/2005/05/seattle-genetics-update-on-sgn-40.html

High-dose Auto followed by mini-Allo

Autologous and allogeneic hematopoietic cell transplantations (HCT) after high-dose conditioning are curative for many patients with hematologic malignancies. The major limitation of autologous HCT is disease recurrence, while the problem with allogeneic HCT is the restriction to relatively young and otherwise medically fit patients because of complications from high-dose therapy coupled with those from graft-versus-host disease (GVHD). The well-described benefits of graft-versus-tumor (GVT) effects have stimulated the development of conditioning regimens with attenuated doses of chemoradiotherapy that may provide both a degree of cytoreduction before allografting (reduced intensity) and facilitate allogeneic cell engraftment through immuno-suppression (nonmyeloablative). Both reduced-intensity and nonmyeloablative approaches seek to exploit GVT activity of donor cells to eradicate cancer. Because of intrinsic or acquired insensitivity of some malignancies to standard dose chemotherapy and the limitations of GVT effects in eradicating large tumor burdens, high-dose autologous HCT has been used before reduced-intensity and nonmyeloablative allogeneic HCT. This approach appears to improve response rates for malignancies such as multiple myeloma and lymphoma, while avoiding morbidity and mortality of high-dose allogeneic HCT. This review details the rationale, benefits and limitations of this approach.

Maris MB, Storb R.Fred Hutchinson Cancer Research Center, Seattle, Washington
PMID: 16269862 [PubMed - in process]

IMF Christmas Cards

Interim clinical results for MGCD0103

November 15, 2005 - MethylGene Inc. (TSX:MYG), today announced interim results regarding MGCD0103, its isotype-selective HDAC inhibitor for cancer, during the 18th EORTC-NCI-AACR (European Organisation for Research and Treatment of Cancer, National Cancer Institute, American Association for Cancer Research) International Conference on Molecular Targets and Cancer Therapeutics in Philadelphia. Ongoing clinical data for MGCD0103 in solid tumours demonstrated prolonged disease stabilization in three patients. Of particular note, is the apparent lack of significant hematological and cardiac side effects with MGCD0103. Data disclosed at the conference included the chemical structure of MGCD0103, the specific HDAC isoforms targeted by MGCD0103, the synergistic antitumour activity of MGCD0103 combined with gemcitabine in pancreatic and lung cancer models in vivo, and the synergistic anticancer activity of MGCD0103 with interferon alpha in multiple myeloma cell lines.

As described in Poster A172, "Epigenetic Regulation of IFNs Activity in Multiple Myeloma by the Isotype-Selective HDAC Inhibitor MGCD0103," the combination of MGCD0103 with interferon alpha synergistically induced apoptotic death of multiple myleoma cell lines.

Source: http://www.methylgene.com

Monday, November 28, 2005

Quadramet & Velcade combo clinical trial

Cytogen Corporation (Nasdaq: CYTO) today announced the initiation of a multicenter Phase I clinical trial to investigate the use of QUADRAMET® (samarium Sm-153 lexidronam) in combination with bortezomib (Velcade®, Millennium Pharmaceuticals, Inc.) for the treatment of multiple myeloma. The clinical study will evaluate the safety profile and preliminary incidence and duration of clinical benefits of bortezomib in combination with QUADRAMET.

More Quadramet info can be found at
http://myelomic.blogspot.com/2005/11/quadramet-information.html

What should Myelomics eat?

Here is the listing of vegetables from the report entitled "Lipophilic and Hydrophilic Antioxidant Capacities of Common Foods in the United States" from the Journal of Agricultural Food and Chemistry (2004), based on Total Antioxidant Capacity per serving:
  1. Small red beans 13727 (dry)
  2. Red kidney beans 13259 (dry)
  3. Pinto beans 11864 (dry)
  4. Artichoke 7904 (cooked)
  5. Russet potatoes 4882 (raw), 4649 (cooked)
  6. Black beans 4181 (dry)
  7. Raab broccoli 2621 (raw), 1322 (cooked)
  8. Navy beans 2573 (dry)
  9. Red cabbage 2359 (cooked), 788 (raw)
  10. Red potato 2339 (raw), 2294 (cooked)

Others include

Blackeye peas 2258 (dry), White potatoes 2257 (raw) 1870 (cooked), Asparagus 2021 (raw) 1480 (cooked), Yellow pepper 1905 (raw), Beets 1886 (raw), Orange sweet pepper 1830 (raw), Yellow onions 1281 (cooked) 823 (raw), Red leaf lettuce 1213 (raw), Sweet potatoes 1195 (cooked) 1173 (raw), Radishes 1107, Red sweet pepper 1072 (raw) 576 (cooked), Spinach 1056 (raw), Eggplant 1039 (raw), Red onion 917 (raw), Broccoli 982 (cooked) 700 (raw), Carrots 741 (raw) 171 (cooked), Green pepper 664 (raw) 418 (cooked), Green leaf lettuce 620 (raw), Corn 561 (raw) 434 (canned) 428 (frozen), Pumpkin 560 (raw), Tomatoes 552 (cooked) 415 (raw), Sweet onion 492 (raw), Green peas 480 (frozen) 326 (canned), Cabbage 476 (raw), Butterhead lettuce 427 (raw), Romaine lettuce 396 (raw), Celery 344 (raw), Cauliflower 324 (raw), Lima beans 301 (canned), Baby carrots 262 (raw), Snap beans 197 (canned) 147 (raw) Iceberg lettuce 144 (raw), Cucumber 74 (unpeeled) 60 (peeled)

The antioxidant capacity is affected by cooking. For example, the russet potato has a TAC/serving of 4882 (raw) and 4649 (cooked), whereas red cabbage has a TAC/serving of 788 (raw) and 2359 (cooked).

Just because a vegetable has a low antioxidant rating doesn't mean it isn't packed with a wide range of beneficial phytonutrients (aka phytochemicals). For example:

  • onions and beans contain Quercetin (a flavonoid)
  • carrots, peppers and tomatoes contain Carotenoids
  • tomatoes contain Lycopene
  • carrots contain Beta-carotene and Lutein
  • cruciferous vegetables contain sulforaphane and dithiolthiones
More information on the benefits of vegetables can be found at the Pytochemical Glossary
http://www.phytopia.com/cookbook/glossary3.htm
and the USDA Food and Nutrition information center
http://www.nal.usda.gov/fnic/etext/000102.html

Sunday, November 27, 2005

Breast cancer advance with myeloma implications

Richmond, Va. (Nov. 14, 2005) — Two new drugs, when combined, killed up to 75 percent of breast cancer tumor cells in mice and suppressed the regrowth of tumors, according to researchers at the Virginia Commonwealth University Massey Cancer Center.

The findings, published online Nov. 14 in the journal Cancer Biology and Therapy, may also have implications for prostate cancer, lymphoma, myeloma and other hematologic cancers.

Paul Dent, Ph.D., associate professor of biochemistry and radiation oncology, led the team. This new study translates its 2002 research that showed early success in the lab and more recently was tested in animals.

In this new study, researchers combined two novel drugs, UCN-01 and a MEK 1/2 inhibitor, which are known to inhibit protein kinases, part of tumor survival signaling pathways.

“In addition to potently inhibiting cells and suppressing tumor growth, these drugs are also part of a modern class of drugs that are less toxic to non-cancerous cells,” said Dent. “We are eager to move these exciting findings from the labs to patients.”

When studied separately, the drugs only killed a small percent of the cells to which they were exposed. Combined, however, the result was quite startling.

“Within five days, we saw profound tumor cell death,” Dent said. “Three researchers in the group operated the same studies independently, and they all saw very similar results.”

The research was funded by the U.S. Department of Defense and the National Institutes of Health. Dr. Dent holds the Universal Corp. Distinguished Professorship in Cancer Cell Signalling.

The first author on the paper was William Hawkins, M.S., a VCU research specialist with appointments in biochemistry, anatomy and neurobiology.

To view the abstract and access the full study, visit http://www.landesbioscience.com/journals/cbt/abstract.php?id=2286.

###

About the VCU Massey Cancer Center The VCU Massey Cancer Center, one of 60 National Cancer Institute-designated research institutions, is VCU’s focal point for basic and clinical cancer research, education, prevention and cancer health care. Since 1975, Massey has served as an internationally recognized center of excellence. Its 175 doctors and researchers are dedicated to improving the quality of human life by developing effective means to prevent, control and ultimately to cure cancer. Visit Massey online at www.vcu.edu/mcc/

Thursday, November 24, 2005

MMRF: Novel Drug Screening

There are many "libraries" of FDA-approved drugs and other compounds that may hold potential to treat myeloma. When we learned they had not been tested in myeloma, we immediately set into action an innovative drug screening program of these drugs against known myeloma targets. We are now working closely with leading academic institutions to rapidly screen these compounds, and by February of 2006, we will know which types of compounds show potential activity in myeloma.

Source: MMRF mailing

MMRF: Multiple Myeloma Genomic Initiative

Recognizing that new genomic technologies now present unprecedented opportunities in advancing myeloma research and drug discovery, we are especially proud to lauch the Multiple Myeloma Genomic Initiative.

This flagship genomic mapping program--a multi-million dollar undertaking--will enable researchers to determine what genes and proteins play a role in the disease's onset and progression, to learn how specific patients respond to therapies, and to identify new druggable targets for the disease. Unique and novel, this pioneering research effort will accelerate the pace of myeloma discovery.

Source: MMRF mailing

Monday, November 21, 2005

ZIO-102 data

Ziopharm Oncology, Inc. announced today the publication of abstracts on its lead product candidate, ZIO-101. The preclinical abstracts are published and available online in Blood, the official journal of the American Society of Hematology. The abstracts include:

  • Abstract 5163: "In vitro activity of a novel organic arsenical (S-dimethylarsino-glutathione, ZIO-101) against multiple myeloma," by Lawrence Boise, Ph.D. and coworkers, University of Miami. In this study, the cytotoxic properties and mechanism of action of ZIO-101 were compared to arsenic trioxide (ATO) in four multiple myeloma cell lines. Data suggest that both ZIO-101 and ATO kill myeloma cells but that different modes of action may be involved. Cancer cells resistant to ATO may respond to ZIO-101.
  • Abstract 4446: "Comparison of uptake and intracellular induced structural changes of arsenic trioxide, an inorganic compound, and organic arsenic derivative S-dimethylarsino-glutathione (SGLU; ZIO-101) in NB4 acute promyelocytic leukemia (APL) cells," by Taghi Manshouri of University of Texas M.D. Anderson Cancer Center and coworkers. This study showed intracellular accumulation of atomic arsenic is about eight-fold higher for ZIO-101 than for ATO at comparable extracellular arsenic concentrations. The compounds also appear to have different modes of action for inducing programmed cell death: ZIO-101 is more toxic to mitochondria than ATO. The researchers conclude based on these data that the activity of ZIO-101 against cancers might be different than ATO.

ZIO-101 is a novel organic arsenic product candidate currently in Phase I clinical trials. It is the lead product candidate from a "family" of novel organic arsenic compounds licensed to ZIOPHARM Oncology, Inc. from the University of Texas M. D. Anderson Cancer Center and Texas A&M University. A Phase I/II trial and a Phase II trial for ZIO-101 in advanced myeloma are in the advanced planning stage and will likely be followed with exploratory Phase II trials in other cancers. The Company expects a pivotal registration trial to initiate the first half of 2007. A second organic arsenic from the same licensing arrangement, ZIO-102, is the subject of further preclinical studies.

Source: www.ziopharm.com

Saturday, November 19, 2005

What should Myelomics eat?

I have yet to find a Myelomic doc who will discuss the effects of food on myeloma. There doesn't seem to be any firm evidence that the food we eat has an effect on myeloma (although there are plenty of studies published on the effects of various foods on myeloma cell lines, including several in this blog). This leads me to believe that healthy eating is probably essential to a Myelomic's health.

We are inundated with information pertaining to the health benefits of eating foods which are rich in antioxidants.

In May, 2004, the Journal of Agricultural and Food Chemistry published the first ever definitive listing of the antioxidant capacities of common foods in the U.S. Some of the highlights of this study include:

  • 100 different foods, including fruits, vegetables, nuts, spices and cereals
  • Samples taken directly from U.S. food markets in four different regions, 12 cities and two seasons
  • Consistent analysis through the oxygen radical absorbance capacity (ORAC) assay
  • Measurement of both lipophilic (fat-based) and hyrophilic (water-based) antioxidant compounds

While this analysis cannot be correlated to clinical effects of eating specific foods, generally speaking oxidative stress (free radicals*) has been associated with many diseases, including cancer, heart disease and Parkinson's & Alzheimer's, through numerous studies. Diets rich in fruits and vegetables have been considered to be excellent sources of antioxidants, which are thought to trap free radicals, thereby removing their harmful effects.

Here is the listing of fruits from the report, based on Total Antioxidant Capacity per serving:

  1. Low-bush blueberry 13427
  2. Cultivated blueberry 9019
  3. Cranberry 8983
  4. Blackberry 7701
  5. Raspberry 6058
  6. Strawberry 5938
  7. Red Delicious Apple 5900
  8. Granny Smith 5381
  9. Cherries, sweet 4873
  10. Plums, black 4844

Others include Plums 4118, Gala Apple 3903, Red Delicious Apple (no peel) 3758, Golden Delicious Apple 3685, Fuji Apple 3578, Avocado 3344, Green Cultivar Pear 3172, Red Anjou Pear 2943, Golden Delicious Apple (no peel) 2829, Navel Orange 2540, Red Grapes 2016, Red Grapefruit 1904, Peaches 1826, Green Grapes 1789, Mango 1653, Tangerine 1361, Pineapple 1229, Nectarines 1019, Kiwifruit 698, Cantaloupe 499, Peaches (canned in heavy syrup) 411, Honeydew Melon 410, Watermelon 216

This is not to imply that foods like melons are not beneficial. All fruits contain a wide variety of wonderful nutrients, known as phytochemicals, that our bodies need to stay healthy. For example,

  • Avocado contains monounsaturated fatty acids such as linoleic acid and vitamin E
  • Bananas are rich in potassium
  • Watermelon and Pink Grapefruit contain lycopene
  • Fruits contain dietary fibre and complex carbohydrates

This list should be used to ensure the inclusion of at least some high antioxidant foods in our daily diet. Also, since this is the first definitive study of this nature, we'll need to see if future studies remain consistent.

Further, processing of food can have a large effect on antioxidant qualities. Removal of the peel is one factor that may lower antioxidant capacity, as indicated by lower values in apples where the peel has been removed.

Friday, November 18, 2005

Denosumab increases bone mineral density

Amgen Corp. has announced that twice-yearly subcutaneous injections of denosumab (60 mg), (previously referred to as AMG 162), increased bone mineral density (BMD) in the lumbar spine, total hip, distal 1/3 radius and total body compared to placebo at 24 months. The study also included an open label Fosamax®* (alendronate) arm. Investigators reported on a pre-planned exploratory analysis at the American College of Rheumatology Annual Scientific Meeting in San Diego, California.

The ongoing, multi-center, phase 2 dose-ranging trial includes results from 337 healthy postmenopausal women with low BMD who completed two years of study. Researchers reported denosumab 60mg increased BMD of the lumbar spine by 7.4 percent in women administered the therapy twice yearly and 6.2 percent for Fosamax® 70mg weekly. Across all doses and dosing intervals, denosumab increased the BMD of the lumbar spine by 4.3 to 9.0 percent over baseline.

"The two-year results showed the continued effect of denosumab in increasing bone mineral density in postmenopausal patients with low bone mass," said Michael Lewiecki, MD, clinical assistant professor of medicine, University of New Mexico School of Medicine,
Albuquerque, NM. "These data suggest denosumab, when administered twice a year, may offer a promising alternative for the prevention and treatment of osteoporosis."

Denosumab is designed to target RANK Ligand, a protein that acts as the primary signal to promote bone removal. In many bone loss conditions, RANK Ligand overwhelms the body's natural defense against bone destruction.

Preclinical models have demonstrated that inhibiting RANK Ligand leads to significant improvements in cortical and trabecular bone density, volume and strength.

Denosumab is currently being studied for its potential in a broad range of bone loss conditions including osteoporosis, treatment-induced bone loss, bone metastases, multiple myeloma and rheumatoid arthritis.

"Because denosumab targets RANK Ligand, it functions in a way that is entirely different than other bone loss treatments," said Willard Dere, MD, senior vice president of global development and chief medical officer, Amgen. "We believe its unique, targeted approach to regulating bone loss may have the ability to transform how we treat these conditions."

Occurrence of adverse events was similar among the denosumab, placebo, and Fosamax® groups and showed no new pattern of events in the second year of treatment. No neutralizing antibodies to denosumab were observed throughout the two years.

Source: http://www.amgen.com

Thursday, November 17, 2005

GCS-100 additional clinical trial site

GlycoGenesys, Inc. today announced it has initiated Roswell Park Cancer Institute, (RPCI) Buffalo, New York as a clinical site for its Phase I/II dose escalation trial in patients with multiple myeloma. The trial is designed to evaluate the safety and efficacy of the Company's drug candidate, GCS-100. RPCI was the first cancer research center in the nation and is a National Cancer Institute designated comprehensive cancer center. The Principal Investigator is Asher A. Chanan-Khan, M.D. Dr. Chanan-Khan's research interests include novel therapies for multiple myeloma and chronic lymphocytic leukemia.

Dr. Chanan-Khan has participated in several important clinical studies in multiple myeloma, including the trials that led to regulatory approval of Velcade® marketed by Millennium Pharmaceuticals and Johnson and Johnson, as well as studies evaluating Celgene's Revlimid ® in patients with CLL.

The trial was designed with the assistance of Dr. Paul Richardson and Dr. Kenneth Anderson at the Dana-Farber Cancer Institute, based upon pre-clinical work conducted in Dr. Anderson's laboratory and recently published in Cancer Research 2005; 65:(18). This research shows that GCS-100:

  • Induces cell death in multiple myeloma cells without significant toxicity against normal white blood cells;
  • Directly targets multiple myeloma cells while in the presence of protective bone marrow cells;
  • Triggers cell death in multiple myeloma cells resistant to commonly used anti-cancer agents including dexamethasone, melphalan, doxorubicin, and Velcade®; and
  • Has additive and/or synergistic effect when combined with caspase-activating agents such as dexamethasone.

Wednesday, November 16, 2005

Quadramet information

Cytogen Corporation today announced that an abstract relating to its flagship product QUADRAMET(R) (samarium Sm-153 lexidronam) has been accepted for
presentation at the upcoming 47th Annual Meeting of the American Society of Hematology (ASH) and has been posted by ASH on the ASH website,
http://www.hematology.org. The abstract is scheduled for presentation at the ASH Annual Meeting, which will be held December 10-13, 2005, in Atlanta, GA.

The abstract, entitled: "Synergistic Activity of the Proteasome Inhibitor PS-341 with Non-Myeloablative 153-Sm-EDTMP in a Syngeneic, Orthotopic Model of
Multiple Myeloma" (A. Goel, A. Dispenzieri, et al.), is scheduled for presentation by clinical investigators.

The abstract can be accessed online as follows at http://www.hematology.org: click on "The 2005 ASH Annual Meeting abstracts are
now available online," register as a user, enter the search term "153-Sm-EDTMP" in the search box, and click on "go."

QUADRAMET is indicated for the relief of pain in patients with confirmed osteoblastic metastatic bone lesions that enhance on radionuclide bone scan.
QUADRAMET is an oncology product that pairs the targeting ability of a small molecule, bone-seeking phosphonate (EDTMP) with the therapeutic
potential of radiation (samarium Sm-153). Skeletal invasion by prostate, breast, multiple myeloma, and other cancers often creates an imbalance between
the normal process of bone destruction and formation. QUADRAMET selectively targets such sites of imbalance, thereby delivering radioactivity to areas of
the skeleton that have been invaded by metastatic tumor. QUADRAMET has many characteristics that the company believes are
advantageous for the treatment of pain arising from metastatic bone disease, including early onset of pain relief (patients may experience pain relief
within the first week with maximal relief generally occurring at three to four weeks after injection), predictable and reversible bone marrow toxicity or
myelosuppression, ease of administration, and length of pain relief, lasting an average of four months in responding patients. QUADRAMET is administered
as a single intravenous injection, usually on an outpatient basis, and exhibits selective uptake in bone with little or no detectable accumulation in
soft tissue.

QUADRAMET Safety Profile
QUADRAMET causes bone marrow suppression. In clinical trials, white blood cell counts and platelet counts decreased to a nadir of approximately 40% to
50% of baseline in 123 (95%) of patients within 3 to 5 weeks after QUADRAMET, and tended to return to pretreatment levels by 8 weeks. Because of the
unknown potential for additive effects on bone marrow, QUADRAMET should not be given concurrently with chemotherapy or external beam radiation therapy unless
the clinical benefits outweigh the risks. Blood counts should be monitored weekly for at least 8 weeks, or until recovery of adequate bone marrow
function. Non-hematologic adverse events that occurred in 5% or more of patients and greater than placebo were plain flare (7%), diarrhea (6%),
infection (7%), spinal cord compression (6.5%), arrhythmias (5%), and hematuria (5%). Patients who receive QUADRAMET should be advised that for
several hours following administration, radioactivity will be present in excreted urine. To help protect themselves and others in their environment,
precautions need to be taken for 12 hours following administration.

A copy of the full prescribing information for QUADRAMET, including warnings, precautions, adverse events and other safety information, may be
obtained in the U.S. from Cytogen Corporation by calling toll-free 800-833-3533 or by visiting the web site at http://www.cytogen.com, which is not part
of this press release.

Source: Cytogen corporate web site http://www.cytogen.com/

Tuesday, November 15, 2005

A step towards FDA approval for Thalomid

Celgene Corporation today announced the U.S. FDA issued an approvable letter in response to the Company's sNDA for multiple myeloma. The FDA has requested revised product labeling with the specific indication of newly diagnosed multiple myeloma and updated safety information, as well as some additional patient information to finalize its review.

The THALOMID sNDA is based on results from a large Phase III randomized Eastern Cooperative Oncology Group study comparing thalidomide plus dexamethasone to dexamethasone alone in previously untreated multiple myeloma patients.

(From the Celgene Corporate web site http://www.celgene.com/

Monday, November 14, 2005

Marine bacteria shows potential as myeloma therapy

Kills blood cancer cells with low toxicity in preclinical studies

An anti-cancer compound derived from bacteria dwelling in ocean-bottom sediments appears in laboratory tests to be a potent killer of drug-resistant multiple myeloma cells, and potentially with less toxicity than current treatments, report Dana-Farber Cancer Institute researchers in the November issue of Cancer Cell.

The experimental compound, NPI-0052, has been found to block or inhibit cancer cells' proteasomes from working effectively. The proteasome work as a cell's "garbage disposal," chewing up and disposing of old, unwanted proteins. With their proteasome jammed, cells die from the backup of damaged proteins.

"Proteasome inhibition is a key therapeutic target and bortezomib (Velcade) was the first in a new class of compounds in multiple myeloma. NPI-0052 is a novel proteasome inhibitor with a chemical structure and action that is distinct from bortezomib, and has the promise of being even more effective for patients," says Kenneth Anderson, MD, director of the Jerome Lipper Multiple Myeloma Center at Dana-Farber, and senior author of the report.

The compound will be moved into Phase I clinical trials in early 2006, say officials of Nereus Pharmaceuticals in San Diego, the developer of NPI-0052. The compound will be tested as a single agent and subsequently in combination with other treatments.

Though less toxic than conventional chemotherapy, bortezomib does have significant side effects in some myeloma patients, including altered blood counts and nerve pain. In some patients, the disease can be resistant or become resistant to bortezomib.

Because NPI-0052 and bortezomib attack the same intracellular target in different ways, the Dana-Farber researchers contend that combining these two agents might be more effective than using either therapy alone – and be better tolerated by patients as well.

In preclinical studies, NPI-0052 blocks a wider range of proteasome activities than bortezomib, say the researchers, and works at lower doses. NPI-0052 also appears to be less toxic to normal cells. Bortezomib is currently given by intravenous infusion. "NPI-0052 can be given orally, although the first clinical trials will be using the intravenous route," says Paul Richardson, M.D, who is also a co-author in this study and will be leading the Phase-I clinical trial at Dana-Farber.

NPI-0052 was discovered by William Fenical, PhD, and his collaborators at The Scripps Institute of Oceanography during the fermentation of Salinispora, a new class of marine gram-positive bacteria identified in sediment samples from the ocean floor. The substance has shown strong anticancer properties in laboratory tests. Nereus Pharmaceuticals holds an exclusive license to the compound for drug development.

Experiments with NPI-0052 began at Dana-Farber in 2003, said Dharminder Chauhan, PhD, lead author of the paper along with Laurence Catley, PhD. When added to cells from patients whose disease was resistant to both standard drugs and bortezomib, the compound efficiently killed the cells. Analyses showed that NPI-0052 and bortezomib express different profiles for inhibiting the three major proteasome activities.

In mice implanted with human myeloma tumor cells, NPI-0052 was well tolerated, prolonged survival and significantly reduced the rate of cancer recurrences. Because NPI-0052 and bortezomib block the proteasome in different ways, the researchers tested them together on myeloma cells. They found that the cancer cells were killed more effectively by the combination than either compound alone – without additional toxicity to normal cells.

"This is a laboratory advance that shows clinical promise," says Dr. Chauhan. "We think this is going to be the '2006 Model' of proteasome inhibitors."

Michael Palladino, Jr., PhD, chief technical officer of Nereus Pharmaceuticals, said that the company plans to file an investigational new drug (IND) application by the end of the year, with trials at several centers – including Dana-Farber – starting in early 2006.

Sunday, November 13, 2005

Promising advance in breast cancer with myeloma implications

Two new drugs, when combined, killed up to 75 percent of breast cancer tumor cells in mice and suppressed the regrowth of tumors, according to researchers at the Virginia Commonwealth University Massey Cancer Center.

The findings, published online Nov. 14 in the journal Cancer Biology and Therapy, may also have implications for prostate cancer, lymphoma, myeloma and other hematologic cancers.

Paul Dent, Ph.D., associate professor of biochemistry and radiation oncology, led the team. In this new study, researchers combined two novel drugs, UCN-01 and a MEK 1/2 inhibitor, which are known to inhibit protein kinases, part of tumor survival signaling pathways.

"In addition to potently inhibiting cells and suppressing tumor growth, these drugs are also part of a modern class of drugs that are less toxic to non-cancerous cells," said Dent. "We are eager to move these exciting findings from the labs to patients."

When studied separately, the drugs only killed a small percent of the cells to which they were exposed. Combined, however, the result was quite startling.

"Within five days, we saw profound tumor cell death," Dent said.

###

The research was funded by the U.S. Department of Defense and the National Institutes of Health. Dr. Dent holds the Universal Corp. Distinguished Professorship in Cancer Cell Signalling.

To view the abstract and access the full study, visit http://www.landesbioscience.com/journals/cbt/abstract.php?id=2286.

Saturday, November 12, 2005

Avemar – fermented wheat germ

According to the following web sites, Avemar (fermented wheat germ), a product developed in Hungary, has anti-cancer properties. I found one reference indicating that Avemar's effect on Multiple Myeloma was being studied.
***
Avemar, the product of industrial fermentation of wheat germ, possesses unique cancer-fighting characteristics. Taken orally, Avemar can inhibit metastatic tumor dissemination and proliferation during and after chemotherapy, surgery, or radiation. Benefits of Avemar treatment have been shown in various human cancers, in cultures of in vitro grown cancer cells, in the prevention of chemical carcinogenesis, and also in some autoimmune conditions. This document reviews the clinical and experimental results obtained with this extract so far. Special references are made for its safety, including its coadministration with anticancer drugs, as well as for its immunomodulatory activity, its molecular targets, and its use in cancer clinical trials.

Boros LG, Nichelatti M, Shoenfeld Y.

FRCP (Hon.), Head, Department of Medicine `B' and Center for Autoimmune Diseases,
Sheba Medical Center, Tel-Hashomer 52621, Israel. shoenfel@post.tau.ac.il.

PMID: 16126993 [PubMed - as supplied by publisher]

Additional web sites:
http://www.avemarresearch.com/
http://www.avemarresearch.com/pdf/05_Avemar.pdf
http://www.avemarusa.com/
http://www.avemar.com/

IMF gala expected to raise $400,000 for advanced myleoma research

The International Myeloma Foundation—conducting research and providing education, advocacy, and support for myeloma patients, families, researchers, and physicians – announced that it expects to raise $400,000 at its 15th annual “Ribbon of Hope Gala,” today at the Beverly Hilton Hotel. The theme of this year’s Gala will be “Lights, Camera, Cure!” Robert Klein—actor, comedian, director, composer, and author—will provide the featured entertainment. Master of Ceremonies will be television host Robin Leach.

Multiple myeloma is the second most common blood cancer after lymphomas, affecting more than 250,000 people worldwide and its prevalence is increasing. Until recently it was inevitably fatal, but myeloma research is helping lead the new direction of cancer treatment—although there is currently no cure for myeloma, it is an eminently treatable disease allowing patients to live longer and productive lives.

Proceeds from the gala will be used in part to support the ground-breaking research of the evening’s honoree, David B. Agus, M.D., a nationally prominent researcher at Cedars-Sinai Medical Center in Los Angeles. Dr. Agus’ work in the growing field of proteomics is helping to advance personalized medicine, tailoring treatments to individual patients. Funds will also be used to support the Myeloma Foundation’s “Bank on a Cure®,” the first global DNA bank dedicated to applying the new knowledge of the human genome to the advanced study of multiple myeloma.

“Since starting the International Myeloma Foundation 15 years ago, we are proud to have raised nearly thirty million dollars for research and patient education,” said Susie Novis, president of the International Myeloma Foundation. “The pharmaceutical and medical advances in myeloma have had a significant impact. Some of the myeloma patients who started with us are still alive today, which would have been unimaginable when we began back in
1990.”

Added Brian G. M. Durie, M.D., Myeloma Foundation chairman, “These advances encourage us to move ahead, but the relapse rate remains high, so there is much work to be done. Our collaboration with Dr. Agus will help us understand why many patients are still left behind despite these advances in treatment and care.”

Multiple myeloma is often treated with bone marrow transplants as well as a variety of pharmaceuticals. Thalidomide is the most widely prescribed treatment for myeloma. Don Baylor and Mel Stottlemyre, both former Major League Baseball coaches and players continued their coaching after being diagnosed with multiple myeloma. Actor Roy Scheider is reported to have myeloma, as does Geraldine Ferraro the first woman to run for Vice President of the United States who is a long time myeloma survivor.

Friday, November 11, 2005

Buy jewelry to support the MMRF

This year, get a head start on your holiday shopping for that special someone. Your mom, your sister, your wife, your friend -- whoever she may be, she is your symbol of strength and courage.

This holiday season give her the gift that shows her that you care. Explore the MMRF’s exclusive Acorn Jewelry Collection today and you will learn why so many myeloma friends and families wear the acorn with pride.

Our symbol of promise and hope is now yours to give, and hers to wear, in support of the best gift of all - a cure.

Source: http://www.multiplemyeloma.org/events/8.11.html

Thursday, November 10, 2005

Sequential, cycling maintenance therapy for post transplant myeloma

High-dose chemotherapy with autologous stem cell transplantation in patients with newly diagnosed multiple myeloma can prolong survival but is not curative. Maintenance therapy post transplant may prolong the disease-free interval and impact overall survival. We have conducted a phase II pilot study of 28 post transplant myeloma patients treated with a sequential, cycling maintenance regimen. The regimen was designed to include a variety of active myeloma agents chosen for ease of administration to enhance patient compliance and scheduled sequentially to minimize toxicity. The 12-month cycling schedule included dexamethasone (months 1-3); melphalan and prednisone (months 4, 5); cyclophosphamide and prednisone (months 6, 7); alpha-interferon (months 8-10); followed by a drug holiday (months 11, 12). The regimen was generally well tolerated with five patients developing reversible grade III-IV toxicity (diabetes-induced hyperglycemia in four, neutropenia in one). There was one toxic death on study due to non-neutropenic pneumonia and sepsis. Median event-free survival from transplant was 36.9 months (95% CI 23.6 - upper limit not yet reached) with median overall survival not yet reached at a median follow-up of 44 months. This concept of cycling, sequential maintenance with various agents, perhaps including newer biological, targeted agents, warrants further investigation in multiple myeloma.Bone Marrow Transplantation advance online publication, 24 October 2005; doi:10.1038/sj.bmt.1705206.

Chen CI, Nanji S, Prabhu A, Beheshti R, Yi QL, Sutton D, Stewart AK.

Department of Haematology/Oncology, Princess Margaret Hospital, Toronto, Ontario, Canada
PMID: 16247415 [PubMed]

Wednesday, November 09, 2005

American Cancer Society volunteer of the year

Wayne Poulter, 53, will receive the American Cancer Society’s Volunteer of the Year.

Poulter, who was diagnosed with multiple myeloma in December 1997, is quick to point out that he isn't downplaying the seriousness of cancer.

Still, he finds it a bit of a surprise that he is being recognized for the effort he put in to helping those who already helped him.

"My wife and I know an awful lot of volunteers that put in a tremendous amount of effort," he said. "So why would I be chosen? To this minute it doesn't make sense to me. I just enjoy and believe in what we're doing."

Poulter has reason to believe that what he and the American Cancer Society are doing makes a difference.

In 1997 Poulter was feeling some pain in his back and side.

Assuming it was just another bout of kidney stones, he decided to go to the doctor.

Instead he was told that he had an incurable cancer: multiple myeloma, a type of cancer formed by cancerous plasma cells in the blood.

It is the same form of cancer that struck Geraldine Ferraro.

"I didn't know how to pronounce multiple myeloma for 30 days," Poulter said. "I remember calling the American Cancer Society hotline because of the shock of being diagnosed and the number said there was 33- or 36-month life expectancy after being diagnosed. Those were just numbers, but it scared the heck out of me."

Those numbers stuck in his head until a family friend put him in touch with Mel Goldstein, a former professor of Poulter's at Western Connecticut State University. Discussing his diagnosis with Goldstein was, he said "almost serendipitous."

"I was preparing for those three years in my head — what I was going to do to prepare my family and everything. Then I had lunch with Dr. Mel and he told me, do not read any more on the Internet, it's only numbers, it's only stats," Poulter said. "That was my turning point."

Poulter's cancer moved slowly, but after the first year the cancer cells began to grow. It was about two years after his diagnosis that he underwent a stem cell transplant.

Poulter had remained in contact with Goldstein and just a year before his levels began to rise Goldstein had told him that he had begun treatment with the drug thalidomide.

It will be five years in January that Poulter has been on thalidomide and, he said, "I'm still amazed it's kept my cancer at bay all this time — and thankful, by the way."

While it's hard to imagine much good coming from such a potentially deadly disease, Poulter has managed to find a silver lining.

Before his diagnosis Poulter never paid any attention to cancer but after his stem cell transplant he attended his first Relay for Life, in Bethel where his sister-in-law Cheryl Pinkos had formed a team.

Poulter liked the positive environment and has been participating in relays ever since, even becoming involved in relay committees.

His participation in Relay for Life led Poulter to meet a number of other cancer survivors who helped him through his illness and inspired him.

Finally, he decided that the relay wasn't enough. He wanted to do more to help them and to help the doctors, nurses and others who dedicated so much time and energy to cancer patients.

And he knew just the place to do it — the Praxair Cancer Center at Danbury Hospital.

"When I would walk through the Praxair Cancer Center I saw all this wall space and all this aisle space and I got to thinking what it would be like to cancer survivors, relatives, nurses, doctors — anybody that was touched by cancer — if they would submit a piece of art and we displayed that art in the halls, in the aisles and on the walls of the Praxair Cancer Center," he said. "The idea behind Joy of Survival was that maybe someone who has just been diagnosed with cancer will walk out and say, 'Sure, I've just been diagnosed with cancer but look at the life here.

So Poulter put pen to paper and wrote down his vision, writing two or three pages of goals and objectives, preparing to sell the idea to the powers that be at the Community Cancer Center, a collaboration of the American Cancer Society, Praxair Cancer Center and Ann's Place, the home of I CAN cancer support services, where Poulter attended support meetings.

Almost before he knew it all three organizations were on board and the "Joy of Survival" art exhibit was born.

The show, which ran from June 2 though June 30, featured more than 100 pieces of art that cancer survivors and others touched by the disease created to express their experiences.

"It was very, very successful, but it really had nothing to do with me. Maybe I had the idea but the support and the dedication and the hard work of the three groups on this project was just stupendous," he said. "I'm bragging because it's the truth. It was probably the most heartwarming and successful projects I've been involved in."

And, he noted, creating the show as a token of appreciation was the least he could do for the people that not only helped him through the toughest times in his life but helped him to emerge stronger.

Now, he hopes, he can continue to spread some of that hope and optimism to others who find themselves in situations similar to his.

"I'm an example for other survivors that with dedication, a good attitude and family support you can still have a very good, happy life," he said. "I think my wife agrees with me that they can look at me, that after seven years of having an incurable cancer that can be aggressive, that you can still survive this."

Tuesday, November 08, 2005

IBM fights cancer

IBM announced today that it is partnering with three leading cancer research organizations. This collaboration with Memorial Sloan-Kettering Cancer Center, the Molecular Profiling Institute, and the Centre Hospitalier Universitaire Sainte-Justine Research Center aims to accelerate cancer research, diagnosis and treatment.

"This is an excellent multi-sector model that can drive integration of molecular medicine into areas where it's truly needed, including cancer detection, treatment, and ultimately prevention," said Dr. Anna D. Barker, Deputy Director of the National Cancer Institute. "The convergence of advanced technologies and post-genomics science will change cancer medicine in ways we cannot yet envision. Capturing and managing the astounding amounts of information generated from new technologies, and integrating the entire process from bench to the bedside, can help usher in the era of molecular oncology — and provide a catalyst to transform all healthcare."

The integration of data across multiple sources and the generation of personalized feedback are two of the technology areas where IBM is lending its expertise. In collaboration with the following three research organizations, IBM can make a true difference in the way that cancer is studied, treated, understood, and hopefully, one day cured.

Memorial Sloan-Kettering

Funded by a $3 million grant of technology and services from IBM, MSKCC will be the first cancer center with a comprehensive system integrating its hospital data with text mining and related analytical capabilities to spur improvements in treatment. This unified information management environment includes the identification of significant research projects from which knowledge is drawn and applied directly to the patient level, accelerating the impact of research work.

In addition, pathologists at MSKCC are working closely with IBM researchers to create a searchable database for pathology reports. In this project, researchers are working to create a system where information will automatically be extracted into standard formats from millions of pathology reports — past and present — and mapped to a database that will help speed cancer research.

Molecular Profiling Institute

The technology being developed by IBM and MPI will provide clinicians with diagnostic intelligence and analysis to assist them in making molecular distinctions when diagnosing and treating cancer patients. This is a first step to making personalized diagnosis based on phenotype and genomic data possible and will send physicians and clinicians a tailored patient report based on the patient's complete molecular profile.

Sainte-Justine Research Center

IBM's work with Sainte-Justine's, a university teaching hospital affiliated with the University of Montreal, will provide their researchers with real-time access to data, using an IBM technology solution. Clinical data that was once manually extracted from the hospital's patient file will now be electronically transmitted and merged with genomic data to create a Medical Information Repository. This will reduce a query process from days to minutes and allow researchers to develop personalized therapies for various patients and keep longitudinal records.

The work with Sainte-Justine's builds on IBM's work with St. Jude Children's Research Hospital. St. Jude operates an IBM supercomputer system that can perform more than 600 billion operations per second and allows St. Jude to accelerate medical research to find preventions, cures and new treatment options for catastrophic diseases in children, such as cancers, acquired and inherited immunodeficiencies and genetic disorders.

http://www-1.ibm.com/press/PressServletForm.wss

Monday, November 07, 2005

Now I've heard everything

I've recently read a number of reports from Korea claiming that kimchi (fermented cabbage, like sauerkraut) was effective in helping chickens recover from bird flu. Here's the BBC story, which seems to be the first one to report on this.
***
South Korea's spicy fermented cabbage dish, kimchi, could help to cure bird flu, according to researchers.

Scientists at Seoul National University say they fed an extract of kimchi to 13 infected chickens - and a week later 11 of them had started recovering.

The researchers said the results were far from scientifically proven and if kimchi did have the effects they observed, it was unclear why.

South Koreans are reported to be eating more kimchi as a result of the study.

Love it or loathe it, once you have eaten it, you will never forget it. Kimchi is made by fermenting cabbage with red peppers, radishes and a lot of garlic and ginger.

The idea that it could help poultry to fight off bird flu sounds like a dubious folk remedy.

But the theory is being floated by some of Korea's most eminent scientists.

Sunday, November 06, 2005

Cancer treatment: know your options

Earlier this year, Nancy Touhey was snorkeling in the Caribbean with her family - something she never imagined she would be able to do. After getting married in 1992, Touhey was diagnosed with multiple myeloma.

"I was 31 years old, and all I knew was I wanted to live - to have children, and watch them grow up, to be there for them and my husband," Touhey said.

By being proactive in her approach to treatment, she has kept her cancer at bay for 13 years while starting a family and maintaining an active lifestyle.

More cancer patients are learning about the importance of taking a proactive approach to their care. By being a partner with their doctors, patients are choosing treatment options that meet their objectives.

"With more choices available to patients, it is increasingly important for doctors and patients to maintain open communication channels in order to find the right treatment for them," said Susan Braun, President and CEO, CURE Media Group.

Braun says patients should discuss the following questions with their doctors:

  • Do you understand my treatment goals?
  • How do the different options increase chances of survival?
  • Are there any potential side effects that can occur from the treatments - and if so, how can they be managed?
  • How will the treatment impact my daily life (work, family, etc.)?
  • Are there reimbursement programs that can help offset treatment costs?

Touhey and her doctor tried several treatments but remained focused on achieving a balance between an aggressive treatment and minimal side effects to help her maintain an active life. As newer therapies became available, Touhey and her physician adjusted her treatment based on her goals.

In 2003, Touhey's doctor introduced her to a new treatment called Velcade, which seemed to fit her lifestyle. Several months later, Touhey was full of energy and was able to enjoy spending time with her family.

While individual response to Velcade may vary, Touhey is winning the fight against her cancer and is realizing her dreams. "For a cancer patient, hope is when you have options," she said. "And I have been holding onto hope since I was diagnosed in 1992."

Source: Medialink Features
http://www.medialinkfeatures.com/home.aspx?Story=31078

Saturday, November 05, 2005

Bottoms up red wine drinkers

A recent study demonstrates once again, that Resveratrol (polyphenol found in grapes and red wine), shows action against myeloma. Resveratrol inhibits myeloma cell growth, prevents osteoclast formation and promotes osteoblast differentiation.

***
Multiple myeloma is characterized by the accumulation of clonal malignant plasma cells in the bone marrow, which stimulates bone destruction by osteoclasts and reduces bone formation by osteoblasts. In turn, the changed bone microenvironment sustains survival of myeloma cells. Therefore, a challenge for treating multiple myeloma is discovering drugs targeting not only myeloma cells but also osteoclasts and osteoblasts. Because resveratrol (trans-3,4',5-trihydroxystilbene) is reported to display antitumor activities on a variety of human cancer cells, we investigated the effects of this natural compound on myeloma and bone cells. We found that resveratrol reduces dose-dependently the growth of myeloma cell lines (RPMI 8226 and OPM-2) by a mechanism involving cell apoptosis. In cultures of human primary monocytes, resveratrol inhibits ose-dependently receptor activator of nuclear factor-B (NF-B) ligand–induced formation of tartrate-resistant acid phosphatase (TRACP)–positive multinucleated cells, TRACP activity in the medium, up-regulation of cathepsin K gene expression, and bone resorption. These inhibitions are associated with a down-regulation of RANK expression at both mRNA and cell surface protein levels and a decrease of NFATc1 stimulation and NF-B nuclear translocation, whereas the gene expression of c-fms, CD14, and CD11a is up-regulated. Finally, resveratrol promotes dose-dependently the expression of osteoblast markers like osteocalcin and osteopontin in human bone marrow mesenchymal stem cells (hMSC-TERT) and stimulates their response to 1,25(OH)2 vitamin D3 [1,25(OH)2D3]. Moreover, resveratrol up-regulates dose-dependently the expression of 1,25(OH)2D3 nuclear receptor. Taken together, these results suggest that resveratrol or its derivatives deserve attention as potential drugs for treating multiple myeloma.

Patrice Boissy1, Thomas L. Andersen1, Basem M. Abdallah2, Moustapha Kassem2, Torben Plesner1 and Jean-Marie Delaissé1

1 Clinical Research Unit and Division of Hematology, Vejle Hospital, Vejle, Southern Denmark University Network, Denmark and 2 Endocrinology and Metabolism, Odense University Hospital, Odense, Denmark

Requests for reprints: Patrice Boissy, Clinical Research Unit, Lab. L120.1400, Vejle Hospital, Kabbeltoft 25, 7100 Vejle, Denmark. Phone: 45-79-40-66-55; Fax: 45-79-40-68-64; E-mail: patboi@vgs.vejleamt.dk

[Cancer Research 65, 9943-9952, November 1, 2005]
© 2005 American Association for Cancer Research

Alberta politician battles myeloma

Economic Development Minister Clint Dunford said Friday he was diagnosed recently with myeloma, or cancer of the bone marrow.

"My mental spirits are fine. I'm not depressed. And I'm not scared," Dunford, 62, told reporters in Red Deer at the Progressive Conservative party's policy convention.

Dunford, the MLA for Lethbridge West, said the cancer verdict came after months of ongoing discomfort which he wrote off as nothing serious.

"I've been suffering back pain," Dunford said. "This was nothing new. I just thought it was a recurrence of old back injuries, so I was going to chiropractors, and it was actually a chiropractor that got me on the right road." When the chiropractor said his X-ray looked suspicious, Dunford paid for an MRI scan and got the diagnosis last month.

He said he was given several options and chose the most aggressive form of treatment, which will involve stem-cell transplants and chemotherapy.

Premier Ralph Klein said the entire caucus is offering its support and three other ministers, Ed Stelmach, Rob Renner and Lyle Oberg, will share Dunford's duties until he's well enough to return to cabinet.

A philosophical Dunford said he considers himself "young and relatively healthy" and is optimistic that he still has many years ahead.

© The Edmonton Journal 2005

Friday, November 04, 2005

England announces speedier approvals of cancer drugs

Cancer patients are celebrating as England announces quicker approval for life-saving drugs.

Government ministers have sanctioned changes to reduce the approval process for many medicines from an average of 14 months to six. And because the new system can start before a drug has been given marketing and safety approval, some guidance may be issued just two months after licensing.

The move has been forced on them by a groundswell of anger among well-informed patients.

Charities have complained that availability of some drugs, already licensed by European or British regulators, could be held up by two to three years under the current system because they have to take their place in the queue before appraisal starts. The row over Herceptin, whose manufacturers have not even submitted a licence application for its use in early stage breast cancer, has already prompted Patricia Hewitt, the health secretary, to make clear to health managers they will no longer be able to refuse its use on the grounds of cost, providing patients and their doctors believe it will benefit them.

The first five drugs to undergo the new process will be Herceptin, Taxol, MabThera, for non-Hodgkin's lymphoma, and Velcade for multiple myeloma. Another nine, again nearly all cancer treatments, should be appraised up to 15 months earlier than previously planned.

Thursday, November 03, 2005

Nancy Sumberaz new President of MMRF and MMRC

The Multiple Myeloma Research Foundation (MMRF) and the Multiple Myeloma Research Consortium (MMRC) announced on October 27, 2005 that Nancy Sumberaz, a former pharmaceutical marketing executive with over 15 years of experience, has been named President. In a simultaneous leadership action, Executive Director of the MMRF, Scott Santarella took on the additional role of Chief Administrative Officer for the two non-profit organizations.

Sumberaz will report to Kathy Giusti, the founder of the MMRF and MMRC, who will retain her role as Chief Executive Officer. Sumberaz has extensive experience with groundbreaking therapeutic products and will be building on the organization's forward momentum in bringing innovative treatments to market for myeloma patients by aligning corporate and academic research efforts.

"Our commitment to bringing new drugs to market and to improving patient outcomes is unflagging," said Giusti. "Nancy's proven experience and personal dedication to the goals of the MMRF/MMRC make her a tremendous addition to our organization."

Before joining the MMRF/MMRC, Sumberaz served as the president of her own consulting business, Point Pharma, LLC, and as Global Oncology Director and U.S. New Business Development Director of Bayer Corporation. Previously, she held numerous leadership roles during her 11 years of service at Eli Lilly and Company.

Wednesday, November 02, 2005

Millennium announces clinical updates to analysts

From the Millennium corporate website at www.millennium.com

Millennium Pharmaceuticals, Inc. today provided clinical development updates at its annual Analyst Day. Millennium reported key clinical advancements in the development of VELCADE® (bortezomib) for Injection, its market-leading drug in relapsed multiple myeloma. These updates included the use of VELCADE in front line multiple myeloma, mantle cell and follicular lymphoma, non-small cell lung cancer, and key advances with other molecules. The Company also provided further details regarding its refined strategy to shift resources toward the inflammation and oncology development pipeline as well as commercial efforts in oncology.

Oncology Clinical Updates

Robert Tepper, M.D., president of research and development of Millennium, presented details of the Company's product pipeline which includes eight molecules in the clinic; four of which were developed by Millennium scientists.

Non-Hodgkin's Lymphoma

The Company announced today its intention to file a supplemental New Drug Application (sNDA) for VELCADE in mantle cell lymphoma in the second half of 2006. The Company, together with co-development partner, Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (J&JPRD), recently completed a phase II study of VELCADE as a single-agent in mantle cell lymphoma patients. Analysis of the data is currently underway, with final data anticipated in the first half of 2006.

Management also announced completed enrollment of 81 patients in a phase II study of VELCADE in relapsed follicular lymphoma, a type of Non-Hodgkin's lymphoma. The trial compared rituximab alone and in combination with VELCADE. Updated data will be presented at the American Society of Hematology meeting in December of this year. Planning for a phase III study of VELCADE in relapsed follicular lymphoma is underway with a potential start date in the second half of 2006.

Non-Small Cell Lung Cancer

Dr. Tepper presented interim survival data in non-small cell lung cancer from a phase II study of VELCADE as a front line treatment. The analysis, conducted by the Southwest Oncology Group, found that VELCADE in combination with gemcitabine and carboplatin, showed a median five-month progression-free survival and a median 11 month overall survival. Based on these and other results, the Company and J&JPRD are exploring clinical rationale, trial design and funding options for possible next steps.

Second Generation Proteasome Inhibitors

Dr. Tepper unveiled details of the Company's second-generation proteasome inhibitor platform which is a large, ongoing initiative aimed at enhancing safety and efficacy, exploring new boronates and other new chemotypes and developing novel chemistry upstream in the pathway. The Company plans to advance a second-generation proteasome inhibitor development candidate by the end of 2006.

Inflammation Clinical Update

The Company anticipates entering the oral, selective IKK inhibitor, MLN0415, into the clinic next year. This small molecule would inhibit IKK beta similar to VELCADE, by inhibiting NFkB. Preclinical data suggest that this molecule has activity across a variety of diseases including rheumatoid arthritis, multiple sclerosis, and chronic obstructive pulmonary disease. The Company's initial phase I study is expected to begin in the second half of 2006. This molecule is part of the sanofi-aventis development and commercialization collaboration.

About VELCADE

VELCADE is indicated for the treatment of multiple myeloma patients who have received at least one prior therapy. VELCADE is contraindicated in patients with hypersensitivity to bortezomib, boron, or mannitol. VELCADE should be administered under the supervision of a physician experienced in the use of antineoplastic therapy.

Risks associated with VELCADE therapy include new or worsening peripheral neuropathy, hypotension observed throughout therapy, cardiac disorders, gastrointestinal adverse events, thrombocytopenia and tumor lysis syndrome. Women of childbearing potential should avoid becoming pregnant while being treated with VELCADE.

In 331 patients who were treated with VELCADE in a phase III study, the most commonly reported adverse events were asthenic conditions (61%), diarrhea (57%), nausea (57%), constipation (42%), peripheral neuropathy (36%), vomiting (35%), pyrexia (35%), thrombocytopenia (35%), psychiatric disorders (35%), anorexia and appetite decreased (34%), parasthesia (27%), dysesthesia (27%), anemia and headache (26%), and cough (21%). Fourteen percent of patients reported at least one episode of grade 4 toxicity; the most common grade 4 toxicities were thrombocytopenia (4%), neutropenia (2%), and hypercalcemia (2%). A total of 144 patients on VELCADE (44%) reported serious adverse events (SAEs) during the study. The most commonly reported SAEs were pyrexia (6%), diarrhea (5%), dyspnea, pneumonia (4%), and vomiting (3%).

For more information about VELCADE clinical trials, patients and physicians can contact the Millennium Medical Product Information Department at 1-866-VELCADE (1-866-835-2233).

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