Cancer Therapy Center

A New York Times article notes that Amgen, Roche, and Johson & Johnson drugs commonuly used to treat anemia resulting from chemotherapy may make the cancer itself worse. The drug makers were quick to note that the process, designed to reduce the need for blood transfusions and to give patients more energy, is not an approved use of the drug, and that the drugs were both safe and effective when used in applications consistent with their FDA approved uses.

NeoPharm Inc announced a restructuring of its workforce following a late failure of its brain cancer drug earlier this month. The drug, cintredekin besudotox, was slated to be the company’s first commercial product. The restructuring, which will result in 14 employees being dismissed, will save the company about $1.5M over the course of 2007.

The trial data showed that patients receiving cintredekin besudotox had roughly the same survival rate as patients receiving MGI Pharma’s Glidel Wafer treatment, the current industry standard. This resulted in the company suspending future trials, leading to a 73% drop in stock price since.

The company is currently working on liposome-based drugs to treat breast cancer, colorectal cancer, and other advanced tumors.

Reuters notes that Abraxis (maker of Abraxane) published interim data showing tumors were more responsive to Abraxane and patients showed fewer side effects than with competing drug Taxotere.

Interim analysis of the 300-patient Phase II trial showed that 61 percent to 72 percent of patients treated weekly with a low dose and high dose, respectively, of Abraxane responded to the drug, compared with 36 percent given Taxotere every three weeks, the company said.

A dose of Abraxane give once every three weeks resulted in a response rate of just 33 percent.

A Phase III trial is scheduled for the first half of 2007. Both drugs are forms of pacilataxel, developed with the goal of interfering with cancer cell growth.

Medpage has an article noting that breast cancer clinicians seem to be fine tuning their art, with a major decline in morality when using radiotherapy, chemotherapy, and Tamoxifen, an analysis of clinical trial evidence has shown.

The five-year update by the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), presented at the San Antonio Breast Cancer Symposium here by epidemiologist Richard Peto, Ph.D., of the University of Oxford in England, held no surprises but confirmed that radiotherapy, chemotherapy combinations, and tamoxifen were steadily reducing disease mortality. 

 

Overall, said Dr. Peto, breast cancer mortality rates have been dropping worldwide since the late 1980s, likely because of effective treatments, early diagnosis by mammography, better adjuvant treatment, and better treatment for relapse.

While each individual treatment has only moderate success against breast cancer, the treatments combine to be increasingly effective.

CBS News has a story noting that RU-486’s progesterone-blocking ability helps prevent breast cancer in mice carrying a dangerous “cancer gene”, a new study shows. While RU-486 is not safe for long-term use, other progesterone-blocking drugs are on the way to treat women carrying the BRCA1 gene mutation, says UCI Professor Eva Y.H.P. Lee.

“To prevent cancer, many women who are BRCA1 carriers have very traumatic surgery — their ovaries and both breasts are removed,” Lee tells WebMD.

“Many of these women have asked us about clinical use of RU-486, but it would have too many side effects for prevention use,” she says. “However, I am happy to say that for the past three years there have been companies working on more appropriate anti-progesterone drugs.”

Lee and colleagues report their findings in the Dec. 1 issue of Science.

QUEBEC CITY, Nov. 27

PRNewswire-FirstCall

AEterna Zentaris Inc today disclosed additional positive top line Phase 1 results for its cytotoxic conjugate AN-152 in patients with gynaecological and breast cancers. Further data showed the compound’s good safety profile and established the maximum tolerated dose (MTD) at 267 mg/m(2) which will be the recommended dose for a Phase 2 trial. In addition to good safety data, the trial provided a hint of efficacy as disease stabilization and regression of lesions were observed at the 160 mg/m(2) and 267 mg/m(2) dose levels.

Dr. Jurgen Engel, Executive Vice President, Global R&D and Chief Operating Officer at AEterna Zentaris, stated, “This additional data provides further proof of concept that the chemical linkage of doxorubicin and the luteinizing hormone-releasing hormone part of the drug molecule is stable in human blood. Most importantly, we witnessed a good safety profile and a hint of efficacy enabling us to establish a suitable dose for further development of AN-152 in the treatment of various cancers.”

Gilles Gagnon, President and Chief Executive Officer at AEterna Zentaris added, “We are very pleased and now even more encouraged with the latest Phase 1 results for AN-152 which lend further credibility to our very promising oncology platform. By targeting patients suffering from ovarian and endometrial cancer with confirmed LHRH receptor status, we believe we may increase our chances of success for our Phase 2 program in these indications. This targeted approach is an additional example of personalized therapy which is becoming more and more the way of the future.”

About the AN-152 Phase 1 Trial in Gynaecological and Breast Cancers

This ongoing Phase 1 open-label, multi-center, dose-escalation, safety and pharmacokinetic study conducted in Europe, includes 17 patients suffering from breast, endometrial and ovarian cancers with proven luteinizing hormone-releasing hormone (LHRH) receptor status. Patients were administered AN-152 by intravenous infusion over two hours at dosages of 10, 20, 40, 80, 160 and 267 mg/m(2). Patients received at least two treatment courses, 21 days apart.

Results

Dose escalation was stopped at 267 mg/m(2), which is equimolar to a doxorubicin dose of 77 mg/m(2), and declared as maximum tolerated dose (MTD) due to dose-limiting although rapidly reversible hematoxicity (CTC grade 4 leucocytopenia/neutropenia) in two out of six patients. Pharmacokinetic (PK) analyses showed dose-dependent plasma levels of AN-152 and only minor (10%-30%) release of doxorubicin. One complete response (TBC by forthcoming CT scan) and two stable disease out of six patients at the 160 mg/m(2) dose level were reported, while at the 267 mg/ m(2) dose level, one partial response and three stable disease were observed from this group of seven patients.

Conclusion

Infusion of AN-152 is well tolerated in female patients. Disease stabilization and regression of lesions are promising signals for therapeutic activity of the cytotoxic LHRH analog, most probably through receptor-mediated uptake by tumor tissue. Because of the rapid reversibility of the potentially dose-limiting hematoxicity even in patients with multiple prior therapies, the dose of 267 mg/m(2) is going to be recommended for Phase 2 trials with ovarian and endometrial cancer as targeted indications. Ovarian and endometrial cancers are two forms of cancer where LHRH receptors are highly expressed.

Background

Human breast, endometrial and ovarian cancers commonly express receptors for luteinizing hormone-releasing hormone (LHRH-R). High-affinity binding sites for LHRH are found in 52% of human breast cancers, as well as in 80% of human ovarian and endometrial cancers. LHRH-R can be used for targeted chemotherapy with AN-152, in which doxorubicin is linked to (D-Lys(6))-LHRH. Safety pharmacology and toxicity studies in mice, rats and dogs demonstrated a significantly reduced cardiotoxic potential of AN-152 compared with doxorubicin, e.g. no QT prolongation, myocarditis or fibrosis in the appropriate models. The Phase 1 study assessed dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and pharmacokinetics (PK) of AN-152 given once every three weeks in patients with gynaecological and breast cancers.

About Cytotoxic Conjugate AN-152

Targeted cytotoxic peptide conjugates are hybrid molecules composed of a synthetic peptide carrier and a well-known cytotoxic product. The design of these products allows for the specific binding and selective uptake of the cytotoxic conjugates by the LHRH receptor-positive tumors. The binding of cytotoxic conjugates to cancerous cells that express these receptors results in an accumulation of the antiproliferative agent in the malignant tissue. This binding is followed by internalization and retention of the cytotoxic drug in the cells. Therefore, since they target specific cells, cytotoxic conjugates are much less toxic, have less side-effects and are more effective in vivo than the respective radicals in inhibiting tumor growth.

About AEterna Zentaris Inc.

AEterna Zentaris Inc. is a growing global biopharmaceutical company focused on endocrine therapy and oncology, with proven expertise in drug discovery, development and commercialization.

News releases and additional information are available at www.aeternazentaris.com.

Forward-Looking Statements

This press release contains forward-looking statements made pursuant to the safe harbor provisions of the U.S. Securities Litigation Reform Act of 1995. Forward-looking statements involve known and unknown risks and uncertainties, which could cause the Company’s actual results to differ materially from those in the forward-looking statements. Such risks and uncertainties include, among others, the availability of funds and resources to pursue R&D projects, the successful and timely completion of clinical studies, the ability of the Company to take advantage of business opportunities in the pharmaceutical industry, uncertainties related to the regulatory process and general changes in economic conditions. Investors should consult the Company’s quarterly and annual filings with the Canadian and U.S. securities commissions for additional information on risks and uncertainties relating to the forward-looking statements. Investors are cautioned not to rely on these forward-looking statements. The Company does not undertake to update these forward-looking statements.

Canadian scientists say hematopoietic stem cell transplant recipients face a significant long-term risk of developing a second cancer.And that risk say Drs. Genevieve Gallagher and Donna Forrest of the University of British Columbia is greater if the recipients were older at the time of transplant or received stem cells from a female donor.

The study revealed within 10 years of an allogeneic HSCT, the relative risk of a second, solid cancer is nearly twice that of the general population. In addition, the risk of cancer nearly quadruples for patients who were over 40 years of age at the time of transplant or for patients who received stem cells from a female donor.

‘Since the risk of developing a solid neoplasm post-allogeneic transplantation continues to increase with time,’ suggest the authors, ‘extended follow-up will be needed to more fully assess the incidence and risk factors for their development.’

The study is detailed online in the journal Cancer and will be published in the journal`s Jan. 1 print edition.

Copyright 2006 by United Press International

Pharmaceutical Business Review Online has an article noting that Reata’s ongoing phase I trial is showing promising signs of activity on patients with the deadliest form of brain tumor, glioblastoma multiforme.

RTA 744 is a new anticancer drug that crosses the blood-brain barrier and shows significant potential for the treatment of brain cancers. The drug has demonstrated appropriate pharmacokinetics and a safety profile consistent with other drugs in its class.

In the phase I trial, RTA 744 produced positive signs of anticancer activity in multiple patients with recurrent glioblastoma multiforme (GBM). In particular, one patient who has been receiving RTA 744 has experienced complete tumor abrogation, a complete response as measured by repeated MRI imaging. Several other patients have also seen their tumors shrink or stabilize upon treatment with RTA 744. Complete responses are extremely rare in this patient population, noted the company.

Advanced trials are scheduled to begin in 2007, and additional trials have begun on different tumors that have spread to the central nervous system.

CBS News is one of many carrying the news about the FDA’s expanded approval of Herceptin for treating breast cancer.

The breast cancer drug Herceptin received expanded federal approval Thursday to include treatment of some women after they have undergone surgery.

In two clinical trials, women given the drug along with chemotherapy had fewer relapses in the three years after surgery — either to remove a lump or the whole breast — than those just given standard chemotherapy, the Food and Drug Administration said in announcing the additional approval. The drug is made by Genentech Inc. of South San Francisco, Calif.

In 1998, the FDA approved Herceptin to treat breast cancer after it had spread to other parts of the body. Thursday’s approval expands its use to women with cancer in the breast or lymph nodes that has been surgically removed, the FDA said.

Only patients with HER-2 positive tumors, and who do have heart failure or a weak heart, should be given the drug, also known as trastuzumab.

A recent study has shown that fierfighters are more likely to develop many types of cancer, specifically testicular, non-Hodgkin’s lymphoma, prostate, and myeloma, when compared to cancer rates among the general population. Experts recommended that firefighters should take precautions when fighting fires, particularly if they’ve removed their protective gear or breathing apparatus, as exposure to carcinogenic toxins occur around (but not necessarily in) the fire area.

The study, which will appear in the November issue of Journal of Occupational and Environmental Medicine, used existing data from over 110,000 firefighters and 32 previous studies to analyze rates of 20 different cancers. Experts concluded that long term exposure to carcinogens such as benzene, diesel exhaust, chloroform, soot, styrene, and formaldehyde - chemicals that can be inhaled or absorbed through the skin - caused a significant increase in risk.

Notably, the risk of testicular cancer increased 100% for firefighters, with multiple myeloma and non-Hodgkin’s lymphoma both having a 50% increase in risk, and a 28% increase in risk for prostate cancer.