Ovarian Cancer

PHILADELPHIA--Women with advanced ovarian cancer had 50% longer survival when they received a first-line regimen combining paclitaxel (Taxol) and cisplatin (Platinol), says William P. McGuire, MD, and his colleagues in the Gynecology Oncology Group (GOG).

The authors offer a comprehensive overview of familial cancer risk counseling, providing both a general definition of this new genetic counseling specialty and specific components of the counseling process. Genetic counseling is, by and large, a referral service, and this is also true of cancer risk counseling. This places great importance on the health-care provider's ability to recognize families who may be at increased risk for an inherited form of cancer and should be referred for cancer risk counseling. It seems reasonable, therefore, to consider the issues relevant to making such a referral, including information on collecting an initial cancer history, strategies for handling a positive history, and the realities of DNA-based testing.

The authors have compiled an excellent summary of the basic components of cancer risk counseling and the role of the genetic counselor in this process. They note that such counseling may have a different scope, depending on the individual's level of risk. They also point out that the approach to each case tends to be unique, due to individual psychological concerns, interpretation of family history and available risk data, and options for genetic testing and prevention or early detection. I would like to expand on the topics discussed in four major areas: counseling cancer survivors, the role of oncologists and primary-care physicians in cancer risk counseling, informed consent issues, and directions of current and future research.

Drs. Lerman and Croyle provide a quite thorough review of an area in need of continuing research-ie, patients' behavioral and emotional responses to genetic testing for cancer susceptibility. The authors present current information on what we do and don't know about the psychological characteristics of individuals likely to undergo testing, possible adverse reactions, issues specific to the genetic counseling process, family coping and adaptation, and possible ways of managing psychological sequelae of genetic testing. Admirably, the authors note that much of their discussion should be considered speculative until more empirical data specific to genetic testing is available. Given this "state of the science," I will raise some additional questions based on some of the statements made by Drs. Lerman and Croyle.

During the past few decades, cancer patients have sued their physicians for negligence in diagnosing or managing their disease, based on the charge that the clinician failed to consider the patient's genealogy when trying to arrive at a diagnosis. Other suits have charged that the clinician is liable for failing to investigate other members of the cancer patient's family, regardless of whether they were his or her patients.

As genetic testing for susceptibility to cancer becomes more widely available, cancer-care providers will become more involved in counseling patients about cancer risks and the meaning of genetic test results. As a result, oncologists and oncology nurses need to be aware of the unique psychological issues and challenges posed by genetic testing for cancer susceptibility. This paper first describes a psychological profile of individuals who are likely to opt for such testing, based on extrapolation from studies of people at high risk of cancer.

Increased knowledge about inherited susceptibility for cancer and the identification of genes associated with cancer risk has increased the need for individuals with training in genetics to work closely with oncology professionals in the familial cancer arena. Genetic counselors can provide a variety of useful services: They may function as clinical coordinators of a family cancer risk counseling (FCRC) program and serve as study coordinators on research teams.

Multiple endocrine neoplasia type 2 (MEN-2) is characterized by medullary thyroid carcinoma in combination with pheochromocytomas and, sometimes, parathyroid adenomas. Since 1993, the psychosocial implications of DNA analysis for MEN-2 have been studied in the Netherlands. This article summarizes the first results of that study. Individuals who applied for DNA analysis cited the need to reduce uncertainty as the major reason for wanting the test. An unfavorable test outcome resulted in anxiety and depression but also relief.

Topotecan HCl, an investigational anticancer drug, has demonstrated significant antitumor activity in previously treated small-cell lung cancer (SCLC) patients, according to European Organization for Research and Treatment of Cancer (EORTC) researchers, who presented phase II trial data at the Eighth European Conference on Clinical Oncology, Cancer Research and Cancer Nursing (ECCO-8) in Paris.

Recent dramatic advances in the understanding of inherited susceptibility to several common adult-onset cancers have made possible the identification of individuals who may be at significantly increased risk of developing malignant disease. These advances may translate into some of the first opportunities for cancer prevention.

This special reference on genetic counseling in cancer is timely, given the explosive progress that has been made in cancer

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.

This paper provides an overview of the current approach to genetic counseling for cancer, using hereditary

An experimental drug designed to help standard chemotherapy drugs maintain their disease-fighting power has cleared its first

The federal government's involvement in cost-effectiveness studies, outcomes measures, and practice guideline development is haphazard, with a number of agencies taking part in the process. The Health Care Financing

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,

The value of prostate cancer screening remains controversial because of the high prevalence of the disease and the fact that many tumors detected through screening are not destined to lead to morbidity or mortality, rendering

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.

Available data show that women tend to overestimate their risk of developing breast cancer. Available models allow for the rapid identification of women who are at increased risk for breast cancer, along with a quantitative

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.

Cisplatin (Platinol) has been the most active agent against ovarian cancer. The question of a relationship between platinum dose and response remains unresolved.

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].

Combining bone marrow transplant with high-dose chemotherapy improves survival rates for women with advanced ovarian

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.