A phase I-II trial of weekly topotecan in the treatment of recurrent cervical carcinoma.

In recent phase III studies, intravenous topotecan (0.75 mg/m(2)) plus cisplatin demonstrated significant progression-free and overall-survival benefits in patients with advanced and recurrent cervical cancer. However, the regimen demonstrated clinically significant myelotoxicity. The current study was undertaken to examine the safety, tolerability, and efficacy of weekly bolus topotecan in patients with advanced or metastatic disease. All patients had biopsy-confirmed disease not amenable to radiation treatment or surgery. Lesions were measurable bidimensionally, and patients had adequate hematologic, hepatic, and renal function. Patients received 3.5 mg/m(2) topotecan intravenously on days 1, 8, and 15 of a 28-day cycle. If no grade 3 or 4 hematologic toxicities occurred, the dose was escalated to 4 mg/m(2) in the third cycle. Safety, tolerability, and response rates were the primary endpoints. In addition to weekly hematologic assessments, Eastern Cooperative Oncology Group status was evaluated monthly, and tumor response was evaluated every alternate cycle. Twenty patients were enrolled and evaluated for toxicity and tumor response. Grade 3 toxicity occurred in 8/48 (17%) treatment cycles. There was only one drug-related adverse toxicity that required a dose reduction. Grade 1/2 hematologic toxicities were rare and only accounted for 1 (2%) of the dose delays (1 week). Two (10%) patients achieved stable disease for a mean of 5.3 months. The weekly bolus topotecan regimen used in the current study was well tolerated. Future phase II studies of weekly bolus topotecan in combination with cisplatin in this patient population may be warranted.