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

In Jae Oh, Kyu Sik Kim, Cheol Kyu Park, Young Chul Kim, Kwan Ho Lee, Jin Hong Jeong, Sun Young Kim, Jeong Eun Lee, Kye Chul Shin, Tae Won Jang, Hyun Kyung Lee, Kye Young Lee, Sung Yong Lee

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Abstract

Background: 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. Methods: 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). Results: 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. Conclusions: 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. Trial registration: ClinicalTrials.gov identifier NCT00826644. Date of Registration: January 21, 2009.

Original languageEnglish
Article number690
JournalBMC Cancer
Volume16
Issue number1
DOIs
Publication statusPublished - 2016 Aug 26

Fingerprint

Small Cell Lung Carcinoma
Etoposide
Cisplatin
Disease-Free Survival
Survival
Radiotherapy
belotecan
Drug Therapy
Anemia
Therapeutics
Confidence Intervals
Safety

Keywords

  • Belotecan
  • Chemotherapy
  • Extensive stage disease
  • First-line
  • Phase III study
  • Small cell lung carcinoma

ASJC Scopus subject areas

  • Oncology
  • Genetics
  • Cancer Research

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Belotecan/cisplatin versus etoposide/cisplatin in previously untreated patients with extensive-stage small cell lung carcinoma : A multi-center randomized phase III trial. / Oh, In Jae; Kim, Kyu Sik; Park, Cheol Kyu; Kim, Young Chul; Lee, Kwan Ho; Jeong, Jin Hong; Kim, Sun Young; Lee, Jeong Eun; Shin, Kye Chul; Jang, Tae Won; Lee, Hyun Kyung; Lee, Kye Young; Lee, Sung Yong.

In: BMC Cancer, Vol. 16, No. 1, 690, 26.08.2016.

Research output: Contribution to journalArticle

Oh, In Jae ; Kim, Kyu Sik ; Park, Cheol Kyu ; Kim, Young Chul ; Lee, Kwan Ho ; Jeong, Jin Hong ; Kim, Sun Young ; Lee, Jeong Eun ; Shin, Kye Chul ; Jang, Tae Won ; Lee, Hyun Kyung ; Lee, Kye Young ; Lee, Sung Yong. / Belotecan/cisplatin versus etoposide/cisplatin in previously untreated patients with extensive-stage small cell lung carcinoma : A multi-center randomized phase III trial. In: BMC Cancer. 2016 ; Vol. 16, No. 1.
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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 = "Background: 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-na{\"i}ve patients with previously untreated ES-SCLC. Methods: 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). Results: 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. Conclusions: The RR to the BP regimen was non-inferior to the EP regimen in chemotherapy- and radiotherapy-na{\"i}ve 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. Trial registration: ClinicalTrials.gov identifier NCT00826644. Date of Registration: January 21, 2009.",
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author = "Oh, {In Jae} and Kim, {Kyu Sik} and Park, {Cheol Kyu} and Kim, {Young Chul} and Lee, {Kwan Ho} and Jeong, {Jin Hong} and Kim, {Sun Young} and Lee, {Jeong Eun} and Shin, {Kye Chul} and Jang, {Tae Won} and Lee, {Hyun Kyung} and Lee, {Kye Young} and Lee, {Sung Yong}",
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T1 - Belotecan/cisplatin versus etoposide/cisplatin in previously untreated patients with extensive-stage small cell lung carcinoma

T2 - A multi-center randomized phase III trial

AU - Oh, In Jae

AU - Kim, Kyu Sik

AU - Park, Cheol Kyu

AU - Kim, Young Chul

AU - Lee, Kwan Ho

AU - Jeong, Jin Hong

AU - Kim, Sun Young

AU - Lee, Jeong Eun

AU - Shin, Kye Chul

AU - Jang, Tae Won

AU - Lee, Hyun Kyung

AU - Lee, Kye Young

AU - Lee, Sung Yong

PY - 2016/8/26

Y1 - 2016/8/26

N2 - Background: 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. Methods: 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). Results: 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. Conclusions: 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. Trial registration: ClinicalTrials.gov identifier NCT00826644. Date of Registration: January 21, 2009.

AB - Background: 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. Methods: 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). Results: 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. Conclusions: 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. Trial registration: ClinicalTrials.gov identifier NCT00826644. Date of Registration: January 21, 2009.

KW - Belotecan

KW - Chemotherapy

KW - Extensive stage disease

KW - First-line

KW - Phase III study

KW - Small cell lung carcinoma

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