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A Phase II Study of Topotecan in Patients with Squamous Cell Carcinoma of the Cervix: A Gynecologic Oncology Group Study

https://doi.org/10.1006/gyno.2000.6024Get rights and content

Abstract

Objective.The toxicity and activity of intravenous topotecan were assessed in a multicenter Phase II study (GOG 76-U) in patients with advanced, recurrent, or persistent squamous cell carcinoma of the uterine cervix.

Methods. Intravenous topotecan was administered at 1.5 mg/m2 per day for 5 consecutive days every 4 weeks in patients without prior chemotherapy, aside from chemosensitizing agents used in conjunction with radiotherapy. The study required histologic confirmation of primary diagnosis, adequate performance status, and measurable disease to assess response. A two-stage design for accrual was used to allow for early termination of the study should inadequate response or excessive toxicity be an issue. Modifications of dose were based on hematologic toxicity. Treatment was continued until progression of disease was documented or adverse effects prohibited further therapy.

Results. A total of 49 patients were entered on study; of these 5 were never treated, and 1 was not evaluable for response. More than 88% (38 of 43 patients) had received prior radiotherapy. A median of two courses were administered per patient with a range of 1 to 14 cycles. Grade 4 neutropenia occurred in 68% and grade 4 thrombocytopenia in 18% of patients. Nonhematologic toxic effects were infrequent and not dose-limiting. The overall response rate (complete and partial) was 18.6%. The median progression-free survival was 2.4 months.

Conclusions. Topotecan administered at this dose and schedule demonstrated moderate activity albeit at a cost of substantial hematologic toxicity in patients with advanced, recurrent, and persistent squamous cell carcinoma of the cervix.

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    Citation Excerpt :

    The introduction of chemoradiation with cisplatin as the primary treatment of patients with locally advanced cervical cancer as well as the modest survival of the patients with recurrent or metastatic disease despite palliative chemotherapy prompted the investigation of non-platinum compounds activity in cervical cancer. Among several drugs tested in phase II trials paclitaxel (McGuire et al., 1996; Kudelka et al., 1996) – especially in cervical non-squamous carcinomas (Curtin et al., 2001) – camptothecin derivatives irinotecan (Verschraegen et al., 1997; Lhommé et al., 1999; Look et al., 1998a) and topotecan (in 5-days dosage schedules) (Muderspach et al., 2001; Bookman et al., 2000), vinorelbine (Morris et al., 1998) and ifosfamide (Carvellino et al., 1990) showed modest activity in this group of patients treated with cisplatin. The above results also prompted to combine these agents with cisplatin attempting to combinations of paclitaxel and cisplatin (Moore et al., 2004), ifosfamide with mesna and cisplatin (Omura et al., 1997) and topotecan – used in a 3-day regimen at 0,75 mg/m2 to reduce myelotoxicity – with cisplatin (Long et al., 2005) were compared with the established cisplatin monotherapy.

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This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group Administrative Office (CA 27469) and the Gynecologic Oncology Group Statistical Office (CA 37517).

The following Gynecologic Oncology Group institutions participated in this study: University of Southern California Medical Center at Los Angeles, University of Mississippi Medical Center, Indiana University Medical Center, Bowman Gray School of Medicine of Wake Forest University, The Albany Medical College of Union University, University of California Medical Center at Irvine, Eastern Virginia Medical School, The Johns Hopkins Oncology Center, University of Texas M.D. Anderson Cancer Center, and University of Toronto/Sunnybrook Regional Cancer Center.

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To whom correspondence should be addressed at Division of Gynecologic Oncology, 1441 Eastlake Avenue No. 7417, Los Angeles, CA 90033. Fax: (323) 226-2734. E-mail: [email protected]. Address reprint requests to GOG Administrative Office, Suite 1945, 1234 Market Street, Philadelphia, PA 19107.

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