Ovarian Cancer

BETHESDA, Md--Women of Ashkenazi Jewish lineage appear to have a lower risk of breast and ovarian cancer from mutations in the BRCA1 and BRCA2 genes than was first thought, a study from the National Institutes of Health has found.

This special series on cancer and genetics is compiled and edited by Henry T. Lynch, MD, director of the Hereditary Cancer Institute, professor of medicine, and chairman of the Department of Preventive Medicine and Public Health, Creighton University School of Medicine, and director of the Creighton Cancer Center, Omaha, Nebraska. Part I of this three-part series on pancreatic cancer appeared in June 1997. Part II (below) reviews the gene mutations thought to contribute to the development of hereditary pancreatic cancer, and Part III will explores the clinical recognition of a hereditary predisposition to pancreatic cancer.

Radioimmunotherapy allows for the delivery of systemically targeted radiation to areas of disease while relatively sparing normal tissues. Despite numerous challenges, considerable progress has been made in the application of radioimmunotherapy to a wide variety of human malignancies. The greatest successes have occurred in the treatment of hematologic malignancies. Radioimmunotherapy, with or without stem-cell transplant support, has produced substantial complete remission rates in chemotherapy-resistant B-cell lymphomas. Nonmyeloablative regimens have shown so much promise that they are now being tested as initial therapy for low-grade B-cell lymphomas. Although solid tumor malignancies have been less responsive to radioimmunotherapy, encouraging results have been obtained with locoregional routes of administration, especially when the tumor burden is small. Greater tumor-to-normal tissue ratios are achievable with regional administration. Even with intraperitoneal and intrathecal administration, bone marrow suppression remains the dose-limiting toxicity. Ongoing research into new targeting molecules, improved chelation chemistry, and novel isotope utilization is likely to extend the applications of this strategy to other tumor types. The potential for radioimmunotherapy will be enhanced if this modality can be optimally adapted for integration with other agents and if the administration method can be tailored to the type and distribution of malignancy. [ONCOLOGY 11(7):979-987, 1997]

Theoretically, effective regional cancer chemotherapy should afford the opportunity to deliver a significantly higher concentration of a cytotoxic agent than is possible with systemic administration of the same agent. Furthermore, regional chemotherapy should cause its greatest stress on the site of administration, producing a lesser burden of toxicity on the whole body.

With its poor prognosis, ovarian cancer remains a disease in search of definitive treatment. Although paclitaxel (Taxol) has improved the outlook, advanced ovarian cancer still has a 5-year mortality rate of 65%. The real problem, according to

New knowledge about the normal function of the BRCA1 gene, various mutations of which have been shown to cause breast and ovarian cancers, may help researchers develop treatments for both hereditary and sporadic disease. Jeffrey T.

The Society of Surgical Oncology surgical practice guidelines focus on the signs and symptoms of primary cancer, timely evaluation of the symptomatic patient, appropriate preoperative evaluation for extent of disease, and role of the surgeon in

The explosive increase in the apparent incidence of prostate cancer in the United States (which is due, in large measure, to wider efforts at early detection) has been accompanied by a dramatic stage migration, which can also be attributed to the increased use of prostate-specific antigen (PSA).

BOCA RATON, Fla--Topotecan (Hycamtin) and other non-cross-resistant drugs appear to be good salvage therapy for patients with recurrent ovarian cancer, Robert F. Ozols, PhD, said at the annual meeting of the Network for Oncology Communication and Research.

Dr. Schuchter's article explores the theoretical and practical aspects underlying the concept of cytoprotection, which has been recently introduced into the therapeutic armamentarium. Cytoprotection is contrasted with the related strategy of rescue, which has been widely applied since the cytokines granulocyte colony-stimulating factor (G-CSF, filgrastim [Neupogen]) and granulocyte-macrophage colony-stimulating factor (GM-CSF, sargramostim [Leukine, Prokine]) obtained FDA approval.

A total of 332 patients with advanced non-small-cell lung cancer were randomized by the European Organization for Research and Treatment of Cancer Lung Cancer Cooperative

The administration of intensive chemotherapy according to a rigid schedule improves response rates and duration of response. However, dose-limiting toxicities and resulting delays in therapy often interfere with therapy

When administered as a single agent in pretreated patients with advanced breast cancer, paclitaxel (Taxol) exhibits remarkable antitumor activity. This trial was undertaken to compare paclitaxel with standard

Paclitaxel (Taxol) has aroused considerable interest for its high single-agent activity in breast cancer and novel mechanism of action. Epirubicin (Farmorubicin), the 4'epimer of doxorubicin (Adriamycin), also has high activity in

PHILADELPHIA--The Board of Directors of the National Comprehensive Cancer Network (NCCN) has elected Robert C. Young, MD, to the position of Chairman of the Board. Dr. Young, currently president of the Fox Chase Cancer Center, is internationally known for his work in the treatment of lymphoma and 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.