title: Phase I clinical trial of alternating belotecan and oral etoposide in patients with platinum-resistant or heavily treated ovarian cancer.
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. Belotecan (0.5 mg/m/day) was administered daily (days 1-5) followed by etoposide (50, 75 mg/day) for up to 5 days (days 6-10) every 3 weeks. Dose-limiting toxicities (DLT) were defined as follows: grade 4 neutropenia less than 1 week; either neutropenic fever less than 24 h or sepsis; grade 4 thrombocytopenia; and grade of at least 3 nonhematologic toxicity except alopecia. At the first dose level (50 mg) of etoposide, none of the three patients developed DLT, whereas DLT was observed in two of three patients at the next dose level. Thus, the dose level was reduced to 50 mg, and another three patients were enrolled. DLT was found in one of six patients who received etoposide at the dose level of 50 mg/m. 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. The combined regimen of belotecan followed by oral etoposide showed promising activity in platinum-resistant or heavily pretreated ovarian cancer patients at the dose level of 50 mg of oral etoposide.
authors.affiliation: Center for Uterine Cancer, Research Institute and Hospital, National Cancer Center, Gyeonggi-do, Korea.
authors.forename: Jong Ha
authors.initials: JH
authors.lastname: Hwang
authors.forename: Heon Jong
authors.initials: HJ
authors.lastname: Yoo
authors.forename: Myong Cheol
authors.initials: MC
authors.lastname: Lim
authors.forename: Sang-Soo
authors.initials: SS
authors.lastname: Seo
authors.forename: Sang-Yoon
authors.initials: SY
authors.lastname: Park
authors.forename: Sokbom
authors.initials: S
authors.lastname: Kang
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy; D005260:Female; D006801:Humans; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D010534:Peritoneal Neoplasms / Q000188:drug therapy; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome
chemical_list: C116963:belotecan; D005047:Etoposide; D002166:Camptothecin