The results of a new study demonstrate that one-third of patients with recurrent ovarian cancer who are categorized as platinum-sensitive respond to treatment with topotecan (Hycamtin). The multicenter trial, conducted by the Gynecologic Oncology Group (GOG) and published in the March issue of the Journal of Clinical Oncology, is the first to specifically evaluate the efficacy of topotecan in platinum-sensitive patients (defined in this study as those who experience a relapse 6 or more months after prior treatment).

The results suggest that topotecan may be an alternative to platinum-based retreatment for this population. Patients treated with multiple courses of platinum-based chemotherapies are at increasing risk for cumulative adverse events with each additional course of therapy.

Effective and Tolerable Alternative

The study elicited a response rate of 33%, with an additional 48% of patients demonstrating stable disease. The median duration of response for all responders was 11.2 months.

“Given its noncumulative toxicity profile and the response rates seen in this study, Hycamtin offers patients an effective and tolerable alternative to retreatment with first-line agents,” said lead investigator William McGuire, MD, director of chemotherapy services, Gynecologic Oncology Center, Mercy Medical Center, Baltimore, and clinical professor of medicine, University of Mississippi School of Medicine, Jackson, Miss. “The encouraging response rate and median duration of response seen in this study further indicate that use of Hycamtin, already known to be an active drug in ovarian cancer, offers another therapeutic option in platinum-sensitive patients.”

Trial Protocols

The study enrolled 48 patients who were given topotecan intravenously for 30 minutes at a starting dose of 1.5 mg/m² daily for 5 consecutive days every 3 weeks. Patients had received no more than two prior platinum-based treatment regimens and had intervals of at least 6 months between the most recent platinum therapy regimen and study entry. Dose level modifications allowed for dose reductions to 1.0 mg/m² when significant hematologic toxicity was unresponsive to granulocyte colony-stimulating factor (G-CSF [Neupogen]) and dose increases to 2.0 mg/m²for grade 0 or 1 hematologic toxicity in the prior course of therapy.

Of patients enrolled in the study, 46 were evaluable for response and 47 for safety. Among the patients responding to treatment with topotecan, there were two complete responses and 13 partial responses. The median time to response was 2.5 months, or three courses, and the median progression-free interval in all patients was 9.6 months.

Adverse Events

Severe neutropenia occurred in 91% of patients and was associated with fever in 15% of patients. G-CSF was administered to 45% of patients during subsequent courses of therapy. Severe thrombocytopenia was seen in 23% of patients. Anemia occurred in 91% of patients, with 44% requiring red blood cell transfusions during therapy.

Fatigue was reported in 32% of patients, causing some to discontinue therapy prior to clinical progression. The rate of therapy discontinuation due to fatigue is unique to this study and is unlike that seen in previous studies of topotecan.

“Currently, patients with recurrent ovarian cancer are often retreated with platinum-based therapies, sometimes resulting in cumulative toxicities,” said Dr. McGuire. “These promising study results indicate that using Hycamtin after patients relapse from their initial ovarian cancer treatment may generate responses comparable to those seen with platinum-based retreatment.”

Topotecan should not be used in patients who have a history of allergic reactions to topotecan or any of its ingredients and should not be used in patients who are pregnant or breast-feeding, or those with low blood counts. Side effects may be more severe if topotecan is given with other chemotherapies.