Ovarian Cancer

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Dr. Therese B. Bevers has been named medical director for Clinical Cancer Prevention at The University of Texas M.D. Anderson Cancer Center. The program, in the Division of Cancer Prevention, works to translate medical science and research into applications that make cancer prevention and early detection a reality. Dr. Bevers was formerly medical director of the MediClinic Corporation.

Despite the development of chemotherapeutic agents, radiation techniques, and improved surgical procedures, many women with gynecologic malignancies will die from recurrent disease. In this broad review, Gurski and Steller examine potential vaccine strategies to improve disease control. The use of vaccines in both prophylactic and therapeutic settings is discussed, and a general overview of vaccines directed against both viral and nonviral tumor-associated antigens is presented.

The development of topotecan (Hycamtin) and the encouraging preliminary results of its use in clinical trials are comprehensively reviewed by Takimoto and Arbuck. The successful development of topotecan demonstrates that focused research and developmental efforts by the pharmaceutical industry in anticancer therapeutics can actually “pay off.” Approximately 15 years ago, the prototypic topoisomerase I inhibitor camptothecin was “placed back on the shelf” because it induced severe, unpredictable toxicity when administered as a sodium salt (sodium camptothecin). After recognition that camptothecin was active by virtue of a novel mechanism of action (topoisomerase I inhibition), developmental research efforts at SmithKline Beecham led to the synthesis of a myriad of camptothecin analogs, significant structure-function information, and the ultimate selection of topotecan as a lead camptothecin analog for clinical development.[1-3]

Immune responses are generated in a complex network of cellular and humoral factors. The complexity of this system makes it difficult to generate subsets of cells in vivo that are most effective against cancer cells. The goal of vaccine strategies is to redirect the immune system against cancer cells primarily by generating specific T-cell responses which would be the most effective anti-tumor effector cells.

The article by Drs. Takimoto and Arbuck reviews the chemistry, mechanism of action, pharmacology and clinical trials of topotecan (Hycamtin), one of two topoisomerase I inhibitors approved recently by the FDA. Topotecan was approved for refractory ovarian cancer and irinotecan (Camptosar) for advanced colorectal cancer. These drugs represent a new drug class designed to inhibit topoisomerase I, an enzyme involved in relaxation of torsional strain in supercoiled DNA allowing replication and translation. The authors’ overview is informative and unbiased.

Data from North American clinical trials have shown that vinorelbine (Navelbine) is well tolerated when used as a single agent for the treatment of non-small-cell lung cancer, advanced breast cancer, or ovarian cancer. Myelosuppression is the primary dose-limiting toxicity.

Many of the more commonly observed adverse effects of standard doxorubicin (Adriamycin) are lessened by pegylated liposomal delivery (Doxil). The slow release of doxorubicin into normal tissue cells via this form of liposomal delivery ameliorates its potential for severe alopecia, nausea and vomiting, cardiotoxicity, and myelosuppressive toxicity. Infusion-related acute reactions are managed by slowing infusion rates and thorough dilution and mixing of the infused drug. Vesicant properties normally seen with doxorubicin are absent. Palmar-plantar erythrodysesthesia can be reduced by decreasing the dose or increasing the dosing interval. Many of these side effects are developing a predictable profile and are manageable. Because of its overall reduced toxicity profile, pegylated liposomal doxorubicin may be well-suited for use in combination chemotherapeutic regimens. [ONCOLOGY 11(Suppl 11):54-62, 1997]

After pegylated liposomal doxorubicin (PEG-LD) (Doxil) was shown to be active in ovarian tumors, several trials were developed at the University of Southern California to determine its safety and efficacy in a variety of gynecologic and peritoneal malignancies. Completed phase I and phase II trials have found PEG-LD to be safe and effective in the treatment of platinum- and paclitaxel-refractory epithelial ovarian carcinoma. A new phase II trial is currently underway in similarly refractory patients with ovarian and other related cancers and various degrees of pretreatment. In addition, the efficacy of PEG-LD is being explored in combination with paclitaxel (Taxol), with cisplatin, and with hyperthermia. [ONCOLOGY 11(Suppl 11):38-44, 1997]

ROCKVILLE, Md-The Food and Drug Administration (FDA) has cleared Bristol-Myers Squibb’s Taxol (paclitaxel) Injection for use in the second-line treatment of AIDS-related Kaposi’s sarcoma (KS). Taxol is also approved for second-line use in metastatic breast and ovarian cancer.

BOCA RATON, Fla--Ovarian cancer survivors have formed the National Ovarian Cancer Coalition (NOCC), an organization whose main mission is to prevent deaths from ovarian cancer by advocating for the development of new techniques for early detection and by raising awareness levels about the disease.

NEW ORLEANS--Women seeking BRCA1 testing appear, as a group, to be more distressed and psychologically vulnerable than those who do not wish to be tested, according to two studies from Lombardi Cancer Center, Georgetown University, reported at the American Society of Preventive Oncology annual meeting. The women in the studies were at high risk because of a close family history of breast or ovarian cancer.

Despite a heightened focus of the medical and research community on prostate cancer, many important questions about this disease remain unanswered. These include questions about the possible prevention of prostate cancer, as well as the optimal treatment approaches for localized, locally advanced, metastatic, and hormone-refractory disease. A whole host of prospective, well-designed clinical trials are currently in progress that should answer many of these questions. This review briefly explores some of these unresolved issues and describes ongoing trials designed to address them. [ONCOLOGY 11(8):1-11, 1997]

ASCO--Use of the investigational resistance modulator PSC-833 in combination with paclitaxel (Taxol) is safe and appears to renew paclitaxel response in some patients with refractory advanced ovarian cancer, Abbie L. Fields, MD, said in an ASCO poster presentation of the preliminary results of the phase II study.

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.