abstract: Phase I clinical trial of alternating belotecan and oral etoposide in patients with platinum-resistant or heavily treated ovarian cancer (total 6 patients/phase 1)

Abstract: 
This study was designed to determine the maximum tolerated dose and toxicity profile of belotecan in combination with oral etoposide in patients with platinum-resistant or heavily treated ovarian cancer, fallopian tubal cancer, and primary peritoneal cancer.

"....Thus, the maximum tolerated dose was reached (50 mg of oral etoposide) and the trial was terminated. The response was evaluable in nine patients and an objective response was observed in four patients (44%) including two complete responses."

Phase II Clinical Study of the Combination Chemotherapy Regimen of Irinotecan Plus Oral Etoposide for the Treatment of Recurrent Ovarian Cancer

OBJECTIVE: To evaluate the efficacy and safety of the combination chemotherapy regimen of irinotecan plus oral etoposide for the treatment of patients with recurrent ovarian cancer after previous treatment with platinum and taxane agents.
PATIENTS AND METHODS: A total of 42 patients with recurrent ovarian cancer who had an evaluable lesion and provided informed consent for participation in the present study were analyzed. Irinotecan was administered intravenously at a dose of 60 mg/m on days 1 and 15. Etoposide was administered orally at a daily dose of 50 mg/body weight from days 1 to 21. A 28-day period comprised one cycle. The tumor response, adverse events, progression-free survival, and overall survival were examined. Tumor response was evaluated based on the Response Evaluation Criteria in Solid Tumors and the serum CA125 levels (Gynecologic Cancer Intergroup criteria). Adverse events were assessed according to the NCI-CTCAE (version 3.0).
RESULTS: Partial response was observed in 21 patients, stable disease in 14 patients, and progressive disease in 7 patients. The response rate was 50.0%, and the clinical benefit (partial response + stable disease) rate was 83.3%. Hematological toxicities of at least grade 3 severity included leukopenia in 21 patients (50.0%), neutropenia in 22 patients (52.4%), thrombocytopenia in 1 patient (2.4%), anemia in 9 patients (21.4%), and febrile neutropenia in 3 patients (7.1%). Nonhematological toxicities of at least grade 3 severity included queasy feeling in 5 patients (11.9%), vomiting in 3 patients (7.1%), and diarrhea in 2 patients (4.8%). Acute myeloid leukemia occurred in one patient (2.4%).
CONCLUSIONS: It is suggested that combination chemotherapy with irinotecan plus oral etoposide offers significant clinical benefit to patients with recurrent ovarian cancer previously treated with platinum and taxane agents.