P G Rose1, J A Blessing, L Van Le, S Waggoner. 1. Department of Obstetrics and Gynecology, University Hospitals of Cleveland, Cleveland, Ohio, 44106, USA.
Abstract
OBJECTIVE: Previous studies by the Gynecologic Oncology Group have demonstrated no activity with bolus etoposide in squamous cell carcinoma of the cervix. Prolonged oral etoposide, which exploits the schedule dependency of this agent, has demonstrated activity in non-small cell carcinoma of the lung and has been studied in combination therapy with cisplatin. To evaluate prolonged oral etoposide in previously treated squamous cell carcinoma of the cervix, the current Phase II trial was conducted. METHODS: Eligibility included squamous cell cancer of the cervix, measurable disease, allowed no more than one prior chemotherapy regimen which did not include etoposide, WBC >/=3000/microliter, platelet count >/=100, 000/microliter, serum creatinine </=2 mg%, and adequate hepatic function. The starting dose was 50 mg/m2/day (40 mg/m2/day for prior radiotherapy) as a single daily dose for 21 days, every 28 days. Based on toxicity, a dose escalation to a maximum dose of 60 mg/m2/day was prescribed. RESULTS: Twenty-five patients were entered on this study; 24 were evaluable for toxicity. A median of 2 courses was given (range 1-8). All but one had received radiation therapy and 20 had received prior chemotherapy. Oral etoposide was not well tolerated with grade 4 neutropenia occurring in 33.3% and grade 4 thrombocytopenia occurring in 15%. Seven patients were unable to complete their first cycle due to toxicity and 8 patients received only one course of therapy. Of the remaining patients, 6 required dose reductions to 30 mg/m2/day. Only 3 patients were able to be dose-escalated to 50 mg/m2/day. Seventeen patients completed one course of therapy and were evaluable for response, of whom 16 had received prior radiotherapy and 15 prior chemotherapy. Two responses (11.8%) were observed, one complete response and one partial response. Both of these patients had disease in nonirradiated sites and one was chemotherapy-naive. Based on an intent-to-treat analysis, the response rate was 8.3%. CONCLUSION: Prior radiation therapy limited the ability to deliver prolonged oral etoposide. At the maximum tolerated dose, this regimen is not significantly active as second-line chemotherapy in squamous cell carcinoma of the cervix. Copyright 1998 Academic Press.
OBJECTIVE: Previous studies by the Gynecologic Oncology Group have demonstrated no activity with bolus etoposide in squamous cell carcinoma of the cervix. Prolonged oral etoposide, which exploits the schedule dependency of this agent, has demonstrated activity in non-small cell carcinoma of the lung and has been studied in combination therapy with cisplatin. To evaluate prolonged oral etoposide in previously treated squamous cell carcinoma of the cervix, the current Phase II trial was conducted. METHODS: Eligibility included squamous cell cancer of the cervix, measurable disease, allowed no more than one prior chemotherapy regimen which did not include etoposide, WBC >/=3000/microliter, platelet count >/=100, 000/microliter, serum creatinine </=2 mg%, and adequate hepatic function. The starting dose was 50 mg/m2/day (40 mg/m2/day for prior radiotherapy) as a single daily dose for 21 days, every 28 days. Based on toxicity, a dose escalation to a maximum dose of 60 mg/m2/day was prescribed. RESULTS: Twenty-five patients were entered on this study; 24 were evaluable for toxicity. A median of 2 courses was given (range 1-8). All but one had received radiation therapy and 20 had received prior chemotherapy. Oral etoposide was not well tolerated with grade 4 neutropenia occurring in 33.3% and grade 4 thrombocytopenia occurring in 15%. Seven patients were unable to complete their first cycle due to toxicity and 8 patients received only one course of therapy. Of the remaining patients, 6 required dose reductions to 30 mg/m2/day. Only 3 patients were able to be dose-escalated to 50 mg/m2/day. Seventeen patients completed one course of therapy and were evaluable for response, of whom 16 had received prior radiotherapy and 15 prior chemotherapy. Two responses (11.8%) were observed, one complete response and one partial response. Both of these patients had disease in nonirradiated sites and one was chemotherapy-naive. Based on an intent-to-treat analysis, the response rate was 8.3%. CONCLUSION: Prior radiation therapy limited the ability to deliver prolonged oral etoposide. At the maximum tolerated dose, this regimen is not significantly active as second-line chemotherapy in squamous cell carcinoma of the cervix. Copyright 1998 Academic Press.
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