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Ovarian Cancer

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Recent identification of gene mutations responsible for hereditary nonpolyposis colorectal cancer (HNPCC) has made possible the presymptomatic diagnosis of at-risk family members. If DNA testing shows that a family member is a gene carrier, that individual's lifetime cancer risk is approximately 90%. If the test is negative, the family member's cancer risk drops to that of the general population.

The discovery of inherited gene mutations that increase the risk of certain cancers could greatly expand the use of predictive genetic testing in healthy individuals. In families with hereditary forms of cancer, the use of genetic tests to determine whether family members have inherited suseptibility mutations (ISMs} may improve out come.

A better understanding of the biology and biochemistry of the cancer cell has led to the development of various promising new antineoplastic compounds that are now undergoing phase I, II, and III clinical testing. These drugs include topoisomerase I inhibitors, such as camptothecin and its analogs 9-aminocamptothecin, irinotecan, and topotecan; the paclitaxel analog docetaxel; gemcitabine, an antimetabolite structurally related to cytarabine; and fluorouracil prodrugs and other thymidylate synthase (TS) inhibitors.

Ovarian cancer is the leading cause of death from a gynecologic malignancy in the United States. Most patients present with advanced disease and are treated with a combination of surgery and chemotherapy. Recently,

SEATTLE-A group of breast cancer patients treated with tamoxifen (Nolvadex) outside of clinical trials had up to a 60% reduction in their risk of developing cancer in the contralateral breast and no increased risk of ovarian or endometrial cancer, report Linda S. Cook, PhD, and her colleagues at the Fred Hutchinson Cancer Research Center.

Fennelly and Schneider review a controversial area in ovarian cancer management in a comprehensive, objective, and thoughtful manner. This review is particularly timely in light of the ever-increasing number of ovarian cancer patients in whom high-dose chemotherapy, with either bone marrow transplantation or peripheral stem-cell transfusion, is being proposed as a treatment option. The authors support the contention that the majority of such patients are being offered a treatment that has little likelihood of providing a meaningful benefit. The take home message from this review is that outside of an appropriately designed clinical trial, there is no established role for high-dose chemotherapy with hematologic support in any subset of patients with advanced ovarian cancer. At the conclusion of this commentary, I will return to the issue of what constitutes an appropriate clinical trial design to evaluate the efficacy of high-dose chemotherapy in ovarian cancer.

We agree with Drs. Fennelly and Schneider that data from prior clinical trials performed in patients with suboptimally debulked ovarian cancer indicate that increasing the dose intensity of cisplatin (Platinol) does not translate into meaningfully higher response rates, longer response durations, or improved survival. The Gynecologic Oncology Group study is most persuasive in showing that doubling the standard dose of cisplatin and cyclophosphamide (Cytoxan, Neosar) while delivering the same total dose does not improve outcome [1].

SAN FRANCISCO--Enhanced concern by the medical community and by women themselves prompted the National Institutes of Health's Office of Medical Applications of Research to convene last year's consensus conference on ovarian cancer, Vicki Seltzer, MD, said at the annual meeting of the American College of Obstetricians and Gynecologists (ACOG).

SEATTLE--In patients with advanced epithelial ovarian cancer, CA 125 concentrations after two cycles of chemotherapy are a powerful independent predictor of survival, a Southwest Oncology Group Study (SWOG) has shown.

WASHINGTON--Only a screening test that can reliably find stage I tumors will have any real impact on overall ovarian cancer mortality, and transvaginal ultrasound does not appear to fulfill that requirement. Although the technique can detect stage I ovarian cancers, its specificity is not high enough to make it useful as a general screening test, Beth Y. Karlan, MD, said at the American Cancer Society National Conference on Gynecological Cancers.

BALTIMORE--Some 60% to 80% of ovarian cancer patients recur after the first round of treatment, and "only about 15% of ovarian cancer patients who test positive at second-look laparotomy survive as long as 5 years," Karl F. Hubner, MD, of the University of Tennessee, Knoxville, said at a nuclear oncology conference sponsored by the Johns Hopkins Medical Institutions.

ROCKVILLE, Md--The Food and Drug Administration's Oncologic Drugs Advisory Committee (ODAC) has voted unanimously to recommend accelerated approval of Ethyol (amifostine injection) as a cytoprotective agent against cumulative renal toxicities associated with cyclophosphamide (Cytoxan, Neosar) and cisplatin (Pla-tinol) in patients with advanced solid tumors of non-germ-cell origin.