New Drugs May Brighten Ovarian Cancer Picture

With its poor prognosis, ovarian cancer remains a disease in searchof definitive treatment. Although paclitaxel (Taxol) has improved the outlook,advanced ovarian cancer still has a 5-year mortality rate of 65%. The realproblem, according to William P. McGuire III, md, clinical professor ofmedicine at University of Mississippi School of Medicine, is the high rateof relapse even after clinical remission.

Speaking at the 14th Chemotherapy Foundation Symposium, Dr. McGuiresaid that paclitaxel in combination with cisplatin (Platinol) has showna 5-month improvement in progression-free survival and a 12- to 14-monthimprovement in median survival over the previously standard treatment ofcisplatin and cyclophosphamide.

Nonetheless, he said, many patients fail to achieve a major responseto initial treatment, and among those who do, relapse is all too common.

Questions remain about the optimal dose, schedule, and duration of treatmentwith paclitaxel, he added. In his opinion, cisplatin with a prior 24-hourinfusion of paclitaxel should be standard treatment.

The development of new drugs is confounded by the risk of developmentof multidrug resistance, Dr. McGuire said. The taxanes are inducers ofthe MDR gene in vitro, but the in vivo effect has not been establishedin clinical trials. Docetaxel (Taxotere) has been shown to be active inovarian cancer, but problematic fluid retention, somewhat alleviated withsteroids, needs to be worked out, he said.

Among other drugs currently in trials, he mentioned gemcitabine (Gemzar),which he said was easy to combine with other drugs, and had shown someefficacy, though of short duration. Doxorubicin encapsulated in pegylatedliposomes (Doxil) may be useful in combination with cisplatin and paclitaxel,as may oral etoposide (VePesid) and topotecan (Hycamtin).

When questioned about intraperitoneal chemotherapy, Dr. McGuire saidthat it may be effective in patients with low-volume disease. He addedthat pending results of new trials of intraperitoneal chemotherapy, thisapproach may warrant reconsideration.