belotecan and Neutropenia

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.

Topics: Administration, Oral; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Drug Resistance, Neoplasm; Etoposide; Fallopian Tube Neoplasms; Female; Humans; Maximum Tolerated Dose; Middle Aged; Neutropenia; Ovarian Neoplasms; Peritoneal Neoplasms; Thrombocytopenia; Treatment Outcome

Belotecan (Camtobell, CKD602) is a new camptothecin derivative antitumor agent that belongs to the topoisomerase inhibitors. The aim of this phase II study was to evaluate the efficacy and safety of single agent belotecan in patients with small cell lung cancer (SCLC). Patients with previously untreated extensive stage disease (ED) SCLC were entered into the study. Belotecan was given by daily intravenous infusion at 0.5mg/m(2)/day for 5 consecutive days, every 3 weeks. 62 patients were enrolled in this study. The overall response rate to chemotherapy on an intention-to-treat basis was 53.2%. The median overall survival was 10.4 months, the median time to progression 4.6 months, and the 1-year survival rate 49.9%. The most common toxicity was hematologic. Grade 3/4 neutropenia occurred in 71.0% of patients and grade 3/4 thrombocytopenia 12.9%. Non-hematologic toxicity of grade 3 or 4 was low. The results suggest that belotecan is relatively active and well tolerable as single agent in patients with ED SCLC. Further investigations with platinum or other active agents are needed.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Camptothecin; Disease Progression; Female; Humans; Infusions, Intravenous; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Neutropenia; Small Cell Lung Carcinoma; Survival Analysis; Topoisomerase I Inhibitors

The objective of this study was to investigate the efficacy of belotecan, a new camptothecin analog, combined with cisplatin for the treatment of chemotherapy-naive patients with extensive-disease small cell lung cancer (ED SCLC).. Treatment consisted of belotecan 0.5 mg/m(2) daily on Days 1 through 4 and cisplatin 60 mg/m(2) on Day 1 of a 3-week cycle for up to 6 cycles unless there was disease progression, unacceptable toxicity, or patient refusal. Response assessment was done every 2 cycles using the Response Evaluation Criteria in Solid Tumors, and toxicity assessment was done every cycle using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0.. Between September 2006 and March 2008, 30 patients participated in the study. Among them, 21 patients achieved a partial response, and the response rate was 70% (95% confidence interval [CI], 50.6%-85.3%); and, after a median follow-up of 20.2 months, the median progression-free survival was 6.9 months (95% CI, 6.3-7.5 months), and the overall survival was 19.2 months (95% CI, 13.3-25.2 months). Grade 3 and 4 adverse events included neutropenia in 23 patients, thrombocytopenia in 8 patients, febrile neutropenia in 9 patients, nausea in 3 patients, and pneumonia in 3 patients. There was 1 treatment-related death from pneumonia. However, nonhematologic toxicity generally was mild and manageable.. The belotecan and cisplatin combination that was studied demonstrated promising response rates and survival outcomes with a manageable toxicity profile for chemotherapy-naive patients who had ED SCLC. The authors concluded that the combination warrants further randomized trials.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neutropenia; Small Cell Lung Carcinoma

The aim of this study was to determine the maximum tolerated dose (MTD) and therapeutic efficacy of a newly developed CKD-602 topoisomerase I inhibitor and cisplatin in patients with recurrent epithelial ovarian cancer. CKD-602 (0.30 mg/m(2) daily for 5 days) and cisplatin (60 mg/m(2) on day 5) were administered to patients every 3 weeks with dose adjustment of CKD-602 by 0.05 mg/m(2) daily until the MTD was reached. Dose-limiting toxicity was defined as grade >or= 3 neutropenia or thrombocytopenia for more than 4 days or accompanied by fever >or= 38.5 degrees C, infection, hemorrhage, or transfusion; grade >or= 3 nonhematological toxicity except for alopecia, nausea, and vomiting. We enrolled 26 patients with recurrent epithelial ovarian cancer who had measurable disease (MD) estimated by computed tomography scan (n= 12) and nonmeasurable disease (NMD) evaluated by serum CA-125 levels (n= 14). All patients received 188 cycles of CKD-602 and cisplatin with a median number of six cycles per patient (range, 2 to 12). MTD of CKD-602 was 0.30 mg/m(2) daily. The overall response rate was 69.2% (18/26) with 58.3% (7/12) and 78.6% (11/14) in MD and NMD, respectively. Among the responsive patients, 14 were platinum sensitive (14/18, 77.7%) and four were platinum resistant (4/8, 50.0%). The most common toxicity was grade >or= 3 neutropenia developing in 17 patients (65.4%) and 72 cycles (38.3%). Grade 3 nausea and anorexia were the most common gastrointestinal toxicities, developing in 15 cycles (8.0%) of four patients (15.4%) and 10 cycles (5.3%) of five patients (19.3%), respectively. The median disease-free interval was 6 months (range 0-26 months). CKD-602 at a concentration of 0.3 mg/m(2) daily for 5 days and cisplatin at 60 mg/m(2) on day 5 every 3 weeks showed high efficacy, with acceptable toxicity, against platinum-sensitive/resistant recurrent epithelial ovarian cancer.

Topics: Adult; Aged; Anemia; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Epithelial Cells; Female; Humans; Leukopenia; Middle Aged; Nausea; Neoplasm Recurrence, Local; Neoplasm Staging; Neutropenia; Ovarian Neoplasms; Treatment Outcome

Belotecan (Camtobell, Chong Keun Dang Corp, Seoul, Korea; CKD602) is a new camptothecin analogue. This study aimed to investigate the safety and efficacy of single-agent belotecan for small-cell lung cancer (SCLC).. Twenty-seven patients with chemotherapy-naive or chemosensitive SCLC were treated with belotecan 0.5 mg/m(2)/day on days 1-5 of a 3-week cycle. All 27 patients were assessable for toxicity, and 21 patients assessable for response.. Nine patients (42.9%) showed objective tumor responses including one complete response; seven (63.6%) in 11 chemotherapy-naive patients; and two (20.0%) in 10 chemosensitive patients. With a median follow-up of 5 years, median progression-free and survival time for chemotherapy-naive patients were 4.8 months and 11.9 months, respectively, while the corresponding values for chemosensitive patients were 3.3 months and 10.5 months, respectively. The most common toxicity was neutropenia.. Belotecan was active in SCLC patients as a single agent, warranting further investigations of belotecan in combination with platinum or other active agents.

Topics: Aged; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoma, Small Cell; Disease-Free Survival; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Proteins; Neutropenia; Salvage Therapy; Topoisomerase I Inhibitors; Treatment Outcome