Ovarian Cancer

PARIS--A new formulation of doxorubicin in "stealth" liposomes (Doxil) provides durable responses in refractory epithelial ovarian cancer and primary peritoneal cancer, while apparently sidestepping the cardiotoxicity that limits the continued use of free doxorubicin in responding patients, according to two phase II studies performed at the University of Southern California (USC), Los Angeles.

Optimal dosing and scheduling are among the most important issues being addressed in clinical studies of the taxanes. The results to date indicate that there may not be a single administration schedule that produces optimal antitumor efficacy. Instead, the specific doses of the taxanes relative to each schedule and the overall aggressiveness of the dosing schedule should be considered. There appears to be a threshold taxane dose or concentration below which only negligible antitumor activity is observed, as well as a plateau dose or concentration above which no further antitumor activity occurs. The doses at which both threshold effects and plateauing of dose-response curves occur seem to be inversely proportional to the duration of the administration schedule. For paclitaxel (Taxol), it appears that comparable antitumor effects are achieved with both short (1- and 3-hour) and prolonged (24- and 96-hour) schedules as long as equitoxic dosing regimens are used. The majority of clinical studies with docetaxel have used a somewhat aggressive dosing schedule, 100 mg/m² over 1 hour, which marks the outer edge of the dosing envelope, but nonrandomized trial results suggest a dose-response relationship in the 60- to 100-mg/m² dosing range. [ONCOLOGY 11(Suppl):7-19, 1997]

The proven safety profile and antitumor activity of paclitaxel (Taxol) in the treatment of metastatic breast cancer led investigators at Memorial Sloan-Kettering Cancer Center (MSKCC) to further examine the agent's potential in the treatment of advanced breast cancer. Efficacy and tolerability studies of paclitaxel as single-agent therapy were undertaken, along with parallel investigations of quality-of-life parameters. The studies examined the effects of 96-hour infusion schedules of paclitaxel and are currently assessing the feasibility of a weekly 1-hour infusion schedule. Researchers at MSKCC also compared the results of a variety of two- and three-drug paclitaxel-containing regimens to determine possible synergism and better define safety profiles. They examined the combination of paclitaxel and edatrexate, as well as a promising combination of paclitaxel and a monoclonal antibody directed at growth factor receptors. The latter ongoing trial will include both laboratory studies that examine possible cellular mechanisms for the combination's observed synergy and a clinical trial that combines paclitaxel with a monoclonal antibody directed against the epidermal growth factor. In conclusion, the investigators discuss the optimal integration of paclitaxel into doxorubicin/cyclophosphamide (Cytoxan, Neosar)-based adjuvant therapy for node-positive stage II-III resectable breast cancer. [ONCOLOGY 11(Suppl):20-28, 1997]

By engineering proteins that coagulate the blood that feeds malignant tumors, scientists at UT Southwestern Center at Dallas have succeeded in destroying malignancies in mice. This therapy is expected to be effective against all major cancers, with

BETHESDA, Md--Hoping to resolve one of cancer care's ongoing controversies, the National Cancer Institute is launching the first large national study of high-dose chemotherapy for advanced ovarian cancer, to be conducted at dozens of medical centers affiliated with the Gynecologic Oncology Group and other cooperative groups supported by NCI.

In an effort to resolve one of the ongoing controversies in cancer care, the National Cancer Institute (NCI) has launched the first large national study of high-dose chemotherapy for ovarian cancer with transplantation of bone marrow blood stem cells.

ATLANTA-A study of more than 400,000 postmenopausal women has found no increased risk of fatal breast cancer with use of estrogen replacement therapy (ERT). In fact, women who reported ever having used estrogen actually had a 16% decreased risk of dying of breast cancer, Dawn Willis, PhD, MPH, reported for the American Cancer Society (ACS) at a general session of the San Antonio Breast Cancer Symposium.

NASHVILLE-In 1996, delivery difficulties were the major barrier to breast cancer gene therapy, Jeffrey T. Holt, MD, said at a plenary session of the San Antonio Breast Cancer Symposium.

VIENNA--For women with advanced epithelial ovarian cancer who fail one platinum-based regimen, topotecan (Hycamtin) may represent a promising alternative to paclitaxel (Taxol), reported W. W. ten Bokkel Huinink, MD, of the Netherlands Cancer Institute.

COLUMBUS, Ohio--Many of the diagnostic tests and procedures following treatment for breast cancer fail to extend survival, as demonstrated by two randomized, prospective studies and nine retrospective studies, said Victor G. Vogel, MD, MHS, director of the Comprehensive Breast Cancer Program at the University of Pittsburgh.

VIENNA--The identification of genes that predispose to cancer raises two dilemmas for clinical oncologists. The first is whether to offer genetic testing to healthy relatives of cancer patients who carry a culprit gene, and the second, thornier problem is whether advice for healthy carriers should extend beyond avoidance of risk factors and regular screening.

Distinct cellular anomalies have been found with far greater frequency in the ovaries of women at high risk of ovarian cancer than in the ovaries of women whose organs were removed for non-cancer-related reasons. This finding may provide clues to

NEW YORK--Three types of genetic modification--chemosensitization of cancer cells, suppression of oncogene function, and chemoprotection of hematopoietic cells--are under study as a means of improving cancer treatment, Albert Deisseroth, MD, PhD, said at the 15th International Bayer Pharma Press Seminar.

Moving into the final recruitment phase, the researchers of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) are seeking 75,000 more men and women ages 55 to 74 to help them determine whether medical tests to detect some of the most common cancers reduce the number of deaths from these diseases. This largest-ever US cancer screening trial will include a total of 148,000 men and women in 10 cities: Denver, Colorado; Washington, DC; Honolulu, Hawaii; Detroit, Michigan; Minneapolis, Minnesota; St Louis, Missouri; Brooklyn, New York; Pittsburgh, Pennsylvania; Salt Lake City, Utah; and Marshfield, Wisconsin.

WASHINGTON--An analysis from the National Cancer Institute, drawing on data from the Surveillance, Epidemiology, and End Results program (SEER) and from the National Center for Health Statistics, has found a 5-year decline of 2.6% in overall cancer mortality (see chart on page 1).

According to a new study published in the October 1, 1996, issue of Blood, Hycamtin (topotecan hydrochloride) offers a promising new treatment option for patients suffering from myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML). Patients treated with topotecan achieved a complete response rate of 28%, while currently used single-agent therapies have traditionally achieved a complete response rate of only 10% to 15% among this high-risk patient group. Topotecan, a topoisomerase I inhibitor marketed by SmithKline Beecham, is currently indicated for the treatment of patients with recurrent, metastatic ovarian cancer.

Oncologists still have no screening test that reliably can detect ovarian cancer in its early stages, and recent genetic advances, while shedding new light on the disease, have further complicated the issue.

SALT LAKE CITY--Myriad Genetic Laboratories, Inc. and the American College of Surgeons (ACS) have announced a long-term study that will follow the outcomes of patients currently undergoing BRCA1 genetic analysis for breast and ovarian cancer susceptibility.

Strategies for chemopreventative drug development are based on the use of well-characterized agents, intermediate biomarkers correlating to cancer incidence, and suitable cohorts for efficacy studies. Since

The standard approaches of surgery or radiotherapy cure only a minority of patients with esophageal cancer. Because of these poor results and the frequent systemic pattern of recurrences, combined-modality therapy

WASHINGTON--The National Coalition for Cancer Research (NCCR) has activated its 18 member organizations to write to Congress in support of S.1897, the NIH Revitalization Act of 1996. This legislation was introduced in the US Senate by Sen. Nancy Kassebaum (R-KS) to revise and extend certain programs of the NIH, including the National Cancer Institute (NCI).

PHILADELPHIA--New computer software is using an investigational algorithm to translate serial CA 125 values and other risk factors into a single number showing a postmenopausal women's risk of developing ovarian cancer, Steven J. Skates, PhD, assistant professor of medicine and biostatistics, Harvard Medical School, said at his American Society of Clinical Oncology poster presentation.

RICHMOND, Ca--Onyx Pharmaceuticals has announced an extension and expansion of its research alliance with Eli Lilly focusing on BRCA1, the gene linked to increased risk of breast and ovarian cancer. Lilly has exclusive rights to the BRCA1 gene by license from Myriad Genetics, Inc.

CHICAGO--A visit by Her Royal Highness The Princess of Wales to the Lurie Cancer Center of Northwestern University raised more than $1 million to support cancer research and benefit patients (see photo ). The funds will go to the Lurie Cancer Center; Gilda's Club, a support group for cancer patients named for comedian Gilda Radner who died of ovarian cancer in 1989; and The Royal Marsden Hospital, London, of which The Princess is president.

PHILADELPHIA--SmithKline Beecham's Hycamtin (topotecan) has received marketing clearance from the FDA for the treatment of patients with metastatic ovarian cancer after failure of initial or subsequent chemotherapy. It is the first topoisomerase I inhibitor approved for use in the United States.

Endometrial carcinoma was a clinically staged disease until the late 1980s, at which point, staging changed to a surgicopathologically defined system. This change in staging, in turn, altered the clinical management of this

FORT LAUDERDALE, Fla--Although many quality of life measures for cancer have been validated, eg, the FLIC (Functional Living Index-Cancer) and the FACT (Functional Assessment of Cancer Therapy), use of a single instrument facilitates analysis of data obtained at different sites, David F. Cella, PhD, said at the first annual conference of the National Comprehensive Cancer Network (NCCN).

NEW ORLEANS--In combination with cisplatin (Platinol) for treatment of gynecologic malignancies, 3-hour infu-sional paclitaxel (Taxol) might be easier to administer but it produces more peripheral neuropathy than the standard 24-hour infusion, a Cleveland Clinic study shows.

ASCO--Topotecan (Hycamtin), an inhibitor of topoisomerase I, significantly increased time to disease progression--23 weeks vs 14 weeks for paclitaxel (Taxol)--when used as second-line therapy in women with recurrent ovarian cancer, James Carmichael, MD, of the University of Nottingham, said at an ASCO scientific session.

WASHINGTON--University of Pennsylvania researchers have obtained the first "conclusive" evidence linking mutations in the recently cloned BRCA2 breast cancer gene to ovarian cancer, a discovery they say indicates that inheritance plays a significantly greater role in the disease than previously thought.