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Letter to the Editor |
New York University Medical Center, New York, New York, USA
Franco Muggia, M.D., New York University Medical Center, 550 First Avenue, BCD 556, New York, New York 10016, USA. Telephone: 212-263-6485; Fax: 212-263-8210; e-mail: Muggif01{at}med.nyu.edu
Received February 20, 2006; accepted for publication April 3, 2006.
The article entitled "Hematologic Safety and Tolerability of Topotecan in Recurrent Ovarian Cancer and Small Cell Lung Cancer: An Integrated Analysis" by Armstrong et al. in the October 2005 issue of The Oncologist [1] summarizes the data from eight phase II and phase III clinical studies of topotecan (Hycamtin®; GlaxoSmithKline, Philadelphia) given to 879 patients that had stage III/IV ovarian cancer or extensive small cell lung cancer. This analysis supported the use of topotecan at 1.5 mg/m2 per day on days 1–5, every 3 weeks, and concluded that the "results suggest that topotecan may be safely administered for multiple courses" with the primary major side effect being myelosupression, which was noncumulative.
In the same issue, Markman [2] commented that the extremefatigueofthedailydosingregimenat1.5mg/m2per day cannot be overlooked and suggested that lower doses (1–1.25 mg/m2 per day) may help improve the side-effect profile. Safra et al. [3] have recently provided evidence for favorable response rates and median time on study with weekly topotecan. We would like to call attention to the tolerance and efficacy of topotecan by continuous infusion at 0.4 mg/m2 per day for 14–21 days every 4 weeks in heavily pretreated patients with ovarian cancer.
Phase I/pharmacologic and phase II studies of protracted infusion schedules of topotecan as a single agent or in combination with other agents, such as cisplatin, pegylated liposomal doxorubicin, or oxaliplatin [4–9], by our group have already been published. Moreover, we have documented the ability to combine a full 14-day infusion with cisplatin in a highly active first-line regimen [6]. Finally, we have shown that the 14-day schedule of topotecan with oxaliplatin is less toxic and is active in the pre-treated setting [9].
The preclinical background for protracted-infusion schedules was provided by Peter Houghton and coworkers [10, 11]. The logistics of such schedules have improved by theavailabilityofmore‘user-friendly’7-dayBaxterinfusers (rather than battery-run pumps) and by the use of long-acting and effective antiemetics in the HT3 family and aprepitant. Our recent clinical experience with protracted-infusion topotecan in patients with recurrent ovarian or primary peritoneal cancer, after failing multiple agents including other schedules of topotecan, may therefore be of interest.
Ten platinum-resistant patients with epithelial ovarian cancer and a median age of 60 years (Table 1
) recently received topotecan after disease progression on several prior regimens. Six women had received topotecan administered via different schedules (weekly i.v., daily i.v. x 5 days, and oral), while the other four had been exposed to a median of two nonplatinum agents after induction. All received topotecan as a single agent in a 14-day schedule every 28 days at a dose of 0.4 mg/m2 per day, with subsequent schedule adjustments for subjective intolerance (fatigue, nausea) or myelosuppression. Grade 3 and 4 toxicities of this infusion regimen in the 10 patients included grade 3 thrombo-cytopenia in three patients and grade 3 neutropenia in three patients (two of whom also had grade 3 platelet toxicity), all without complications. Red cell transfusions were required every other cycle by three patients, five patients experienced grade 2 fatigue, and subtotal alopecia was also commonly noted. One of the longest responders, patient 1, had failed multiple agents, including carboplatin, pegylated liposomal doxorubicin, gemcitabine, and weekly topotecan, after recurring from her initial induction; she had a gradual decline in CA-125 to a nadir of <10% from the original value, relief of pelvic symptoms, and improved findings on imaging (short of a partial response by Response Evaluation Criteria in Solid Tumors criteria).
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DISCLOSURES |
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ACKNOWLEDGMENT |
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This article has been cited by other articles:
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  D. K. Armstrong In reply. Oncologist, May 1, 2006; 11(5): 531 - 532. [Full Text] [PDF]
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M. Markman In reply. Oncologist, May 1, 2006; 11(5): 532 - 532. [Full Text] [PDF]
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