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Non-Cross-Resistant Agents for Ovarian Cancer

Non-Cross-Resistant Agents for Ovarian Cancer

BOCA RATON, Fla--Topotecan (Hycamtin) and other non-cross-resistant drugs appear to be good salvage therapy for patients with recurrent ovarian cancer, Robert F. Ozols, PhD, said at the annual meeting of the Network for Oncology Communication and Research.

He noted that oncologists are "very good at getting people into a clinical complete remission," using cytoreductive surgery and standard first-line regimens of cisplatin (Platinol) or carboplatin (Para-platin) plus paclitaxel (Taxol). "But the problem is that most of these patients will recur," said Dr. Ozols, senior vice president of medical science, Fox Chase Cancer Center.

For those who recur with drug-sensitive disease, there is no need to switch to non-cross-resistant agents, he said. For patients who recur with drug-resistant or drug-refractory disease, a number of newer non-cross-resistant drugs are available.

These include the topoisomerase I inhibitor topotecan (Hycamtin), oral etoposide (VePesid), gemcitabine (Gemzar), vinorelbine (Navelbine), and liposomal doxorubicin (Doxil), along with two older drugs, hexamethymela-mine (Hexalen) and ifosfamide (Ifex).

In a European trial, Dr. Ozols said, patients with recurrent ovarian cancer who did not receive paclitaxel up-front were randomized to receive topotecan or paclitaxel. The results showed a response rate of 23% for topotecan versus 14% for paclitaxel, response duration of 32 weeks versus 20 weeks, and time to progression of 23 weeks versus 14 weeks.

"Of course," Dr. Ozols said, "all you can really conclude from this type of study is that topotecan is an active agent in recurrent disease." The study is irrelevant to today's practice, he said, since "everyone starts off with a first-line treatment of paclitaxel."

As a second-line treatment, topotecan is usually given at the FDA-approved dosing schedule of 1.5 mg/m2 qd × 5 every 3 weeks. The dose-limiting toxicity in phase I trials was hematologic, primarily neutro-penia. However, Dr. Ozols said that the hematologic problems are both predictable and manageable.

"And since there is no evidence that a higher dose equals a higher response," he said, "you can back off early if there are signs of hematologic toxicity." He even suggests starting with a lower dose if patients have had extensive therapy, and decreasing the dose at the first signs of even mild hematologic toxicity.

The future direction of topotecan use, he said, involves giving it at different schedules, combining it with other agents, and giving it as part of initial therapy.

Dr. Ozols also described a Gynecologic Oncology Group trial of oral etoposide in 70 patients with recurrent ovarian cancer. Platinum-resistant patients had an overall 27% response rate with oral etoposide and platinum-sensitive patients had a 34% response rate.

Gemcitabine, which is approved for use in pancreatic cancer, is currently being studied in Europe where it is showing a 19% response rate in platinum-resistant tumors. There is also evidence of a possible in vitro synergy between gem-citabine and cisplatin.

Results are expected soon for studies in recurrent ovarian cancer of liposomal doxorubicin and the vinca alkaloid vinorelbine, he added.

While there are many trials going on and many agents now available, there is no drug of choice in second-line treatment, Dr. Ozols said. So the criteria for selecting second-line therapy lies in three areas--patient preference, toxicity profile, and oral versus IV.

He recommends selecting a drug and evaluating the patient after two courses of treatment. "If the drug is not working, then try another agent," he said. "The worst we can do is administer a drug that is not effective."

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