title: Belotecan/cisplatin versus etoposide/cisplatin in previously untreated patients with extensive-stage small cell lung carcinoma: a multi-center randomized phase III trial.
abstract: 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.
authors: Department of Internal Medicine, Lung and Esophageal Cancer Clinic, Chonnam National University Hwasun Hospital, 322 Seoyang-ro, Hwasun-eup, Jeonnam, 58128, South Korea.
authors: In-Jae
authors: IJ
authors: Oh
authors: Department of Internal Medicine, Lung and Esophageal Cancer Clinic, Chonnam National University Hwasun Hospital, 322 Seoyang-ro, Hwasun-eup, Jeonnam, 58128, South Korea.
authors: Kyu-Sik
authors: KS
authors: Kim
authors: Department of Internal Medicine, Lung and Esophageal Cancer Clinic, Chonnam National University Hwasun Hospital, 322 Seoyang-ro, Hwasun-eup, Jeonnam, 58128, South Korea.
authors: Cheol-Kyu
authors: CK
authors: Park
authors: Department of Internal Medicine, Lung and Esophageal Cancer Clinic, Chonnam National University Hwasun Hospital, 322 Seoyang-ro, Hwasun-eup, Jeonnam, 58128, South Korea. kyc0923@jnu.ac.kr.
authors: Young-Chul
authors: YC
authors: Kim
authors: Department of Internal Medicine, Yeungnam University Medical Center, Yeungnam University College of Medicine, Daegu, Republic of Korea.
authors: Kwan-Ho
authors: KH
authors: Lee
authors: Department of Internal Medicine, Yeungnam University Medical Center, Yeungnam University College of Medicine, Daegu, Republic of Korea.
authors: Jin-Hong
authors: JH
authors: Jeong
authors: Department of Internal Medicine, Chungnam National University Hospital, Chungnam National University School of Medicine, Daejeon, Republic of Korea.
authors: Sun-Young
authors: SY
authors: Kim
authors: Department of Internal Medicine, Chungnam National University Hospital, Chungnam National University School of Medicine, Daejeon, Republic of Korea.
authors: Jeong-Eun
authors: JE
authors: Lee
authors: Department of Internal Medicine, Yonsei University Wonju Severance Christian Hospital, Yonsei University College of Medicine, Wonju, Republic of Korea.
authors: Kye-Chul
authors: KC
authors: Shin
authors: Department of Internal Medicine, Kosin University Gospel Hospital, Kosin University College of Medicine, Busan, Republic of Korea.
authors: Tae-Won
authors: TW
authors: Jang
authors: Department of Internal Medicine, Inje University Busan Paik Hospital, Busan, South Korea.
authors: Hyun-Kyung
authors: HK
authors: Lee
authors: Department of Internal Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Republic of Korea.
authors: Kye-Young
authors: KY
authors: Lee
authors: Department of Internal Medicine, Guro Hospital, Korea University, Seoul, South Korea.
authors: Sung-Yong
authors: SY
authors: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000401:mortality; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged
chemical_list: C116963:belotecan; D005047:Etoposide; D002945:Cisplatin; D002166:Camptothecin
keywords: Belotecan; Chemotherapy; Extensive stage disease; First-line; Phase III study; Small cell lung carcinoma