Multicenter phase 2 study of belotecan, a new camptothecin analog, and cisplatin for chemotherapy‐naive patients with extensive‐disease small cell lung cancer

Abstract

BACKGROUND: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).METHODS:Treatment consisted of belotecan 0.5 mg/m2 daily on Days 1 through 4 and cisplatin 60 mg/m2 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.RESULTS: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.CONCLUSIONS: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. Cancer 2010. © 2010 American Cancer Society.

Belotecan/cisplatin versus etoposide/cisplatin in previously untreated patients with extensive-stage small cell lung carcinoma: a multi-center randomized phase III trial

“…However, we found a higher proportion of patients with ECOG PS 2 than the study by Noda et al (16 % vs. 8 %). Moreover, the RR in the present study was approximately 10 % lower than previous phase II trials enrolling a smaller number of patients [16–18]. To date, Lim et al have reported the highest RR (73.8 %) with the use of the BP regimen [18].…”

“…To date, Lim et al have reported the highest RR (73.8 %) with the use of the BP regimen [18]. Lee et al reported a median PFS of 6.9 months and a median OS of 19.2 months in patients receiving the BP regimen [16]. In the current study, the degree of the difference in the RR between the two treatment arms was higher in the PP population than the mITT population (18.0 % vs. 13.1 %).…”

“…According to two multi-center phase IIa studies, belotecan monotherapy is an effective modality for the treatment of SCLC in chemotherapy-naïve patients [14, 15]. Moreover, multi-center phase II studies have reported response rates (RR) higher than 70 % and OS greater than 10 months in patients with ES-SCLC receiving belotecan/cisplatin (BP) as a first-line treatment regimen [16–18]. …”

Antitumor activity of CKD-602, a camptothecin derivative, in a mouse glioma model

“…28,31,32 Recently, Lee et al reported that CKD-602 combined with cisplatin delivered excellent results in a multicenter phase II study for patients with small cell lung cancer. 33 The response rate was 70% [95% confidence interval (CI), 50.6-85.3%], 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), and the regimen was associated with tolerable toxicity. Grade 3 and 4 adverse events included neutropenia in 23 of a total of 30 patients, thrombocytopenia in eight patients, febrile neutropenia in nine patients, nausea in three patients, and pneumonia in three patients.…”

Phase II study of belotecan, a camptothecin analogue, in combination with carboplatin for the treatment of recurrent ovarian cancer

“…13 Belotecan, alone or in combination with cisplatin, has demonstrated promising outcomes in some cancers. [14][15][16][17] In recurrent ovarian cancer, use of belotecan as a single agent resulted in a 21%-45% response rate, and using it in combination with cisplatin showed a 47%-69% response rate with acceptable toxicity. Despite these results, there have been no reports on the efficacy of combination treatments, including belotecan and carboplatin.…”