With its poor prognosis, ovarian cancer remains a disease in search of definitive treatment. Although paclitaxel(Drug information on paclitaxel) (Taxol) has improved the outlook, advanced ovarian cancer still has a 5-year mortality rate of 65%. The real problem, according to William P. McGuire III, md, clinical professor of medicine at University of Mississippi School of Medicine, is the high rate of relapse even after clinical remission.
Speaking at the 14th Chemotherapy Foundation Symposium, Dr. McGuire said that paclitaxel in combination with cisplatin(Drug information on cisplatin) (Platinol) has shown a 5-month improvement in progression-free survival and a 12- to 14-month improvement in median survival over the previously standard treatment of cisplatin and cyclophosphamide(Drug information on cyclophosphamide).
Nonetheless, he said, many patients fail to achieve a major response to initial treatment, and among those who do, relapse is all too common.
Questions remain about the optimal dose, schedule, and duration of treatment with paclitaxel, he added. In his opinion, cisplatin with a prior 24-hour infusion of paclitaxel should be standard treatment.
The development of new drugs is confounded by the risk of development of multidrug resistance, Dr. McGuire said. The taxanes are inducers of the MDR gene in vitro, but the in vivo effect has not been established in clinical trials. Docetaxel (Taxotere) has been shown to be active in ovarian cancer, but problematic fluid retention, somewhat alleviated with steroids, needs to be worked out, he said.
Among other drugs currently in trials, he mentioned gemcitabine(Drug information on gemcitabine) (Gemzar), which he said was easy to combine with other drugs, and had shown some efficacy, though of short duration. Doxorubicin(Drug information on doxorubicin) encapsulated in pegylated liposomes (Doxil) may be useful in combination with cisplatin and paclitaxel, as may oral etoposide(Drug information on etoposide) (VePesid) and topotecan(Drug information on topotecan) (Hycamtin).
When questioned about intraperitoneal chemotherapy, Dr. McGuire said that it may be effective in patients with low-volume disease. He added that pending results of new trials of intraperitoneal chemotherapy, this approach may warrant reconsideration.