PROLONGED ORAL ETOPOSIDE IN RECURRENT OR ADVANCED SQUAMOUS-CELL CARCINOMA OF THE CERVIX - A GYNECOLOGIC-ONCOLOGY-GROUP STUDY

Objective, Previous studies by the Gynecologic Oncology Group have dem onstrated no activity with bolus etoposide in squamous cell carcinoma of the cervix, Prolonged oral etoposide, which exploits the schedule d ependency of this agent, has demonstrated activity in non-small cell c arcinoma 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 c ervix, measurable disease, allowed no more than one prior chemotherapy regimen which did not include etoposide, WBC greater than or equal to 3000/mu l, platelet count greater than or equal to 100,000/mu l, seru m creatinine less than or equal to 2 mg%, and adequate hepatic functio n. The starting dose was 50 mg/m(2)/day (40 mg/m2/day for prior radiot herapy) as a single daily dose for 21 days, every 28 days. Based on to xicity, a dose escalation to a maximum dose of 60 mg/m2/day was prescr ibed. Results. Twenty-five patients were entered on this study; 24 wer e 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 neutr openia occurring in 33.3% and grade 4 thrombocytopenia occurring in 15 %, Seven patients were unable to complete their first cycle due to tox icity and 8 patients received only one course of therapy. Of the remai ning patients, 6 required dose reductions to 30 mg/m2/day. Only 3 pati ents were able to be dose-escalated to 50 mg/m(2)/day, Seventeen patie nts completed one course of therapy and were evaluable for response, o f whom 16 had received prior radiotherapy and 15 prior chemotherapy. T wo responses (11.8%) were observed, one complete response and one part ial response, Both of these patients had disease in nonirradiated site s and one was chemotherapy-naive. Based on an intent-to-treat analysis , the response rate was 8.3%, Conclusion. Prior radiation therapy limi ted the ability to deliver prolonged oral etoposide, At the maximum to lerated dose, this regimen is not significantly active as second-line chemotherapy in squamous cell carcinoma of the cervix, (C) 1998 Academ ic Press.