belotecan and Lung-Neoplasms

No novel chemotherapeutic combinations have demonstrated superior efficacy to etoposide/cisplatin (EP), a standard treatment regimen for extensive-stage small cell lung carcinoma (ES-SCLC) over the past decade. We aimed to compare the efficacy and safety of belotecan/cisplatin (BP) and EP regimens in chemotherapy- and radiotherapy-naïve patients with previously untreated ES-SCLC.. We conducted a multi-center, randomized, open-label, parallel-group, phase III clinical study. A total of 157 patients were recruited at 14 centers with 147 patients meeting the inclusion/exclusion criteria and randomized to either BP (n = 71) or EP (n = 76) treatment arms. A non-inferior response rate (RR) in the BP arm, analyzed by intent-to-treat analysis according to Response Evaluation Criteria in Solid Tumors version 1.0 criteria, was used as the primary endpoint. The secondary endpoints were progression-free survival (PFS) and overall survival (OS).. In the BP arm, one patient had a complete response, 41 had a partial response (PR), and 17 had stable disease (SD). In the EP arm, 35 patients had PR and 28 had SD. The RR in the BP arm was non-inferior to the EP regimen in patients with ES-SCLC (BP: 59.2 %, EP: 46.1 %, difference: 13.1 %, 90 % two-sided confidence interval: -0.3-26.5, meeting the predefined non-inferiority criterion of -15.0 %). No significant differences in OS or PFS were observed between the treatment arms. Hematologic toxicities, including grade 3/4 anemia and thrombocytopenia, were significantly more prevalent in the BP arm than the EP arm.. The RR to the BP regimen was non-inferior to the EP regimen in chemotherapy- and radiotherapy-naïve patients with previously untreated ES-SCLC. Hematologic toxicities were significantly more prevalent in the BP group, indicating that BP should be used with care, particularly in patients with a poor performance status. Further studies assessing PFS and OS are required to validate the superiority of the BP regimen.. ClinicalTrials.gov identifier NCT00826644 . Date of Registration: January 21, 2009.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoma, Small Cell; Cisplatin; Disease-Free Survival; Etoposide; Female; Humans; Kaplan-Meier Estimate; Lung Neoplasms; Male; Middle Aged

Belotecan is a new camptothecin analogue and a potent topoisomerase I inhibitor. The aim of this phase II study was to investigate the efficacy and toxicity of belotecan in previously untreated elderly patients with small cell lung cancer (SCLC).. A total of 26 patients, aged ≥65 years, with previously untreated, extensive-stage SCLC were enrolled in the study. Belotecan was administered by daily intravenous infusion at 0.5 mg/m(2)/day for 5 consecutive days every 3 weeks.. The overall response rate and disease control rate of chemotherapy on an intention-to-treat basis were 35 and 54 %, respectively. The median overall survival was 6.4 months, and the median time to progression was 2.8 months. The most common toxicity was hematologic. Grade 3 or 4 neutropenia occurred in 80.8 % of patients, and grade 3 or 4 thrombocytopenia in 15.3 %. Non-hematologic toxic effects of grade 3 or 4 were uncommon.. Belotecan had modest efficacy and well-tolerated toxicity in previously untreated, elderly SCLC patients. Single belotecan could be a promising treatment option, considering its lower toxicity in elderly patients who are unsuitable candidates for platinum plus etoposide chemotherapy.

Topics: Aged; Aged, 80 and over; Camptothecin; Disease Progression; Female; Humans; Infusions, Intravenous; Lung Neoplasms; Male; Neoplasm Staging; Small Cell Lung Carcinoma; Survival Rate; Topoisomerase I Inhibitors; Treatment Outcome

To determine the efficacy and safety of belotecan in combination with cisplatin as first-line chemotherapy for extensive disease of small cell lung cancer (ED SCLC).. Patients with chemotherapy-naïve ED SCLC were eligible if the following criteria were met: age ≥18 years; a measurable lesion; Eastern Cooperative Oncology Group Performance Status (PS) 0-2; and adequate organ function. Each cycle consisted of belotecan (0.5 mg/m(2)/day) on days 1-4 and cisplatin (60 mg/m(2)) intravenously on day 1. The cycle was repeated every 3 weeks until the completion of the 6th cycle, disease progression, or intolerable toxicity.. Thirty-five patients (median age, 68 years) were enrolled: 32 males (91.4%); and PS = 0 (n = 3), PS = 1 (n = 18), and PS = 2 (n = 14). The median number of cycles delivered was 5 (range, 1-6). The relative dose intensity was 70.1% for belotecan and 83.0% for cisplatin. Of 30 evaluable patients, objective response rate was 71.4% (95% confidence interval [CI], 55.7-87.2) by the intent-to-treat principle. The median duration of follow-up was 14.3 months. The median progression-free survival was 5.7 months (95% CI, 3.9-7.5) and the median overall survival was 10.2 months (95% CI, 9.3-11.1). The frequently reported grade 3 or 4 toxicities included neutropenia in 24 patients (68.6%), thrombocytopenia in 10 (28.6%), and anemia in 7 (20.0%). There was no grade 3 or 4 non-hematologic toxicity except three patients (8.6%) with fatigue.. Belotecan and cisplatin combination therapy showed significant efficacy in ED SCLC with improved non-hematologic toxicities.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoma, Small Cell; Cisplatin; Disease-Free Survival; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Survival Rate; 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 as a second-line therapy in patients with small cell lung cancer (SCLC). Patients who were previously treated for SCLC were entered into the study. Belotecan was given by daily intravenous infusion for five consecutive days, every three weeks. Twenty-five patients were enrolled in this study. On an intention-to-treat basis, belotecan induced an overall response rate of 24%, a median overall survival of 9.9 months, a median time to progression of 2.2 months, and a 1-year survival rate of 38.3%. Grade 3/4 neutropenia developed in 88.0% of patients and grade 3/4 thrombocytopenia in 40.0%. Nonhematologic toxicity of grade 3 or 4 was low. The results suggest that belotecan is relatively active and well tolerated as a second-line agent in patients with SCLC.

Topics: Adult; Aged; Antineoplastic Agents; Camptothecin; Female; Humans; Lung Neoplasms; Male; Middle Aged; Small Cell Lung Carcinoma; Survival Analysis; Topoisomerase I Inhibitors; 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

Belotecan is a topoisomerase I inhibitor. This phase II trial was conducted to evaluate the efficacy and toxicity of belotecan in relapsing small-cell lung cancer (SCLC) patients after irinotecan failure.. SCLC patients, who had relapsed at least 3 months after achieving objective response to irinotecan plus platinum chemotherapy, were eligible. Belotecan was administered at a dose of 0.5 mg/m(2)/day for 5 consecutive days every 3 weeks.. Twenty-seven patients were enrolled in this study. Twenty-five patients were evaluated for response, and 27 patients were evaluated for toxicity and survival. The overall response rate was 22%. The median time to progression was 4.7 months (95% CI, 3.6-5.8 months), and the median overall survival was 13.1 months (95% CI, 10.4-15.8 months). The most frequent grade 3/4 toxicities were neutropenia (93%) and thrombocytopenia (48%). There was one treatment-related death due to pneumonia.. Belotecan showed modest activity and manageable toxicities in relapsing SCLC patients in this study which was conducted in Asia. But further study in Caucasian patients is needed.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoma, Small Cell; Disease-Free Survival; Female; Humans; Irinotecan; Lung Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Salvage Therapy; Topoisomerase I Inhibitors

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

Belotecan (Camtobell, CKD602) is a novel camptothecin derivative. This study was designed to determine the maximum tolerated dose (MTD), toxicity profile, and dose-limiting toxicity of belotecan in combination with cisplatin in patients with previously untreated extensive-stage disease small cell lung cancer (SCLC). Furthermore, pharmacokinetics and preliminary antitumor activity against SCLC were evaluated.. Belotecan was administered i.v. as intermittent 30-min infusions on days 1 to 4, starting dose of 0.40 mg/m2/d with increment of 0.05 mg/m2/d. Intrapatient dose escalation was not allowed. Cisplatin (60 mg/m2) was given on day 1. The treatments were repeated every 3 weeks. Pharmacokinetics was determined during the first cycle using noncompartmental pharmacokinetic analysis.. Seventeen chemotherapy-naive patients with extensive-stage disease SCLC were treated. The MTD of belotecan was 0.50 mg/m2/d with the dose-limiting toxicity of grade 4 neutropenia with fever. A partial response was seen in 13 of 17 patients (76.5%). The most common toxicity was neutropenia but nonhematologic toxicity was very favorable. Pharmacokinetic analysis revealed that, at the dose of 0.50 mg/m2/d, plasma clearance of belotecan was 5.78 +/- 1.32 L/h and terminal half-life was 8.55 +/- 2.12 h. Fraction of excreted amount in urine was 37.36 +/- 5.55%. Pharmacokinetics of belotecan was not altered by administration of cisplatin compared with historical control.. The MTD and recommended dose of belotecan for phase II studies was 0.50 mg/m2/d on days 1 to 4 in combination with 60 mg/m2 cisplatin on day 1 every 3 weeks.

Topics: Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Area Under Curve; Camptothecin; Carcinoma, Small Cell; Cisplatin; Cohort Studies; Female; Humans; Lung Neoplasms; Male; Maximum Tolerated Dose; Middle Aged; Time Factors; Treatment Outcome

Belotecan (Camtobell, CKD602) is a new camptothecin-derivative antitumor agent that belongs to the topoisomerase inhibitors. The aim of this study was to evaluate the efficacy and safety of belotecan monotherapy as a second-line therapy in patients with relapsed or refractory small cell lung cancer (SCLC).. Between June 2008 and August 2011, a total of 50 patients with relapsed or refractory SCLC were treated with belotecan 0.5 mg/m for 5 consecutive days, every 3 weeks. We evaluated the overall response rate (ORR), the progression-free survival (PFS), and the overall survival (OS), and toxicity according to sensitivity to initial chemotherapy.. The median age was 66 years (range, 43-84 years) and Eastern Cooperative Oncology Group performance was 0 or 1 in 34 patients (68%) and 2 in 16 patients (32%). Twenty patients (40%) had sensitive relapse and 30 patients (60%) had refractory disease. The ORR, PFS, and OS for sensitive patients were 20% (95% confidence interval [CI], 8-40), 2.8 months (95% CI, 0.53-5.06), and 6.5 months (95% CI, 1.58-11.42), respectively. In the refractory group, the ORR, PFS, and OS were 10% (95% CI, 1-21), 1.5 months (95% CI, 1.25-1.75), and 4.0 months (95% CI, 3.40-4.60), respectively. Most commonly reported grade-3 or -4 adverse events included neutropenia (54%), thrombocytopenia (38%), and anemia (32%).. Belotecan showed modest activity with an acceptable safety profile as a second-line therapy in patients with relapsed or refractory SCLC.

Topics: Adult; Aged; Aged, 80 and over; Camptothecin; Carcinoma, Small Cell; Disease-Free Survival; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Retrospective Studies; Topoisomerase I Inhibitors