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.
