Lawrence M. Prescott, PhD

More than 1000 gynecologic oncologists, medical oncologists, radiation therapists, pathologists, and basic scientists gathered at the 31st Annual Meeting of the Society of Gynecologic Oncologists, held in San Diego, California, on February 5-9, 2000, to hear the latest findings in the prevention, detection, and treatment of women's cancers. Listed below are highlights of some of the innovative therapeutic approaches with particular emphasis on ovarian cancer.

Docetaxel and Carboplatin as Initial Therapy

The combination of carboplatin (Paraplatin®, Bristol Myers Squibb) and docetaxel (Taxotere®, Aventis) is a highly active therapeutic modality for initial treatment of ovarian and fallopian tube cancers, as well as primary peritoneal carcinoma, reported Maurie Markman, MD, chairman, department of hematology/oncology, and director, Cleveland Clinic Cancer Center, Cleveland, Ohio.

A total of 50 women with ovarian cancer (36), fallopian tube cancer (1), or primary peritoneal carcinoma (13) were enrolled in a Phase II trial to assess the safety and efficacy of the docetaxel/carboplatin combination as initial chemotherapy. The patients were treated with initial doses of carboplatin AUC 6 and docetaxel 60 mg/m², repeated on a 21-day schedule times six courses.

Up to the present time, 42 treated women are evaluable, of whom 35 (83%) have shown objective overall responses (either complete or partial) to this chemotherapeutic approach. The regimen is safe and generally well tolerated, with grade 4 neutropenia being the major toxicity, in 60% of patients. There was no grade 4 thrombocytopenia and grade 2 neurotoxicity was noted in only 2% of patients.

Interleukin-2 in Persistent Ovarian Cancer

Outpatient intraperitoneal (IP) infusions of interleukin-2 (IL-2) (Proleukin®, Chiron) appears to be a valuable approach against persistent ovarian cancer after paclitaxel (platinum-based chemotherapy), according to Thomas P. Morrissey, MD, Magee-Women's Hospital/University of Pittsburgh, Pittsburgh, Pennsylvania.

Initially, women underwent surgical evaluation to demonstrate biopsy-proven persistent disease after six or more courses of paclitaxel/platinum-based chemotherapy. Twenty-nine eligible patients with persistent (21) or recurrent (8) ovarian cancer less than 2 cm were treated with 16 weekly IP IL-2 infusions dosed at 6 X 10⁶ IU/m². Twenty-four women have received three or more courses of IL-2 and were considered evaluable for response. Six responses (25%) were confirmed surgically, four complete and two partial responses. In addition, seven patients had stabilization of disease (29%). Two unevaluable patients are still clinically free of disease over one year after therapy. The treatment was relatively well tolerated, with only two patients developing grade 3 abdominal pain and withdrawing from the study. The other six withdrawals were non-drug-related.

Lower Dose Topotecan as Salvage Therapy

Compared to standard approved dosing, topotecan (Hycamtin®, SmithKline Beecham), given at a lower dose, is markedly less toxic and equally as effective in women with recurrent ovarian cancer who are resistant or refractory to platinum and paclitaxel-based chemotherapy, said Michael Rodriguez, MD, assistant professor of reproductive biology, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio.

Twenty-three patients with platinum and paclitaxel resistant or refractory cancer were given topotecan 1.0 mg/m² daily for five days every 21 days, for a median number of five courses. Response and safety were compared to historical controls who had received the standard 1.5 mg/m² daily dose of topotecan.

Twenty-six percent of the patients responded to the lower dose of topotecan versus almost 14% in the historical controls. In addition, the lower dose resulted in significantly less hematological toxicity, a major dose limiting adverse effect previously, with only 48% of women experiencing grade 4 neutropenia compared to 82% of patients in the historical pivotal study.

More information on women's cancer research and the 31st Annual Meeting of the Society of Gynecologic Oncologists can be found at the society's web site at www.sgo.org.

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