Cancer Res Treat.  2019 Jan;51(1):119-127. 10.4143/crt.2018.019.

Randomized Phase III Trial of Irinotecan Plus Cisplatin versus Etoposide Plus Cisplatin in Chemotherapy-Naïve Korean Patients with Extensive-Disease Small Cell Lung Cancer

Affiliations
  • 1Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea. heo1013@snu.ac.kr
  • 2Division of Hematology-Oncology, Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, Korea.
  • 3Department of Internal Medicine, Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.
  • 4Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Seoul, Korea.
  • 5Department of Internal Medicine, St. Vincent's Hospital, The Catholic University of Korea, Suwon, Korea.
  • 6Division of Hematology/Oncology, Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea.
  • 7Division of Hemato-Oncology, Department of Internal Medicine, Veterans Health Service Medical Center, Seoul, Korea.
  • 8Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, Seoul, Korea.
  • 9Department of Hematology-Oncology, Yeungnam University Medical Center, Daegu, Korea.
  • 10Division of Oncology, Department of Internal Medicine, Asan Medical Center, Seoul, Korea.
  • 11Department of Internal Medicine, Daegu Catholic University Hospital, Daegu, Korea.
  • 12Department of Internal Medicine, SMG-SNU Boramae Medical Center, Seoul, Korea.
  • 13Division of Medical Oncology, Chungbuk National University Hospital, Chungju, Korea.
  • 14Division of Hematology-Oncology, Department of Internal Medicine, Hallym University College of Medicine, Kangdong Sacred Heart Hospital, Seoul, Korea.
  • 15Department of Hematology-Oncology, Ajou University Hospital, Suwon, Korea.
  • 16Division of Oncology/Hematology, Department of Internal Medicine, Korea University Anam Hospital, Seoul, Korea.
  • 17Medical Research Collaborating Center, Seoul National University College of Medicine, Seoul, Korea.

Abstract

PURPOSE
This randomized phase III study was designed to compare the efficacy and safety of irinotecan plus cisplatin (IP) over etoposide plus cisplatin (EP) in Korean patients with extensive-disease small-cell lung cancer (SCLC).
MATERIALS AND METHODS
Patients were randomly assigned to receive IP, composed of irinotecan 65 mg/m2 intravenously on days 1 and 8+cisplatin 70 mg/m2 intravenously on day 1 every 3 weeks, or EP, composed of etoposide 100 mg/m2 intravenously on days 1, 2, 3+cisplatin 70 mg/m2 intravenously on day 1, every 3 weeks for a maximum of six cycles, until disease progression, or until unacceptable toxicity occurred. The primary endpoint was overall survival.
RESULTS
A total of 362 patients were randomized to IP (n=173) and EP (n=189) arms. There were no significant differences between IP and EP arms for the median overall survival (10.9 months vs. 10.3 months, p=0.120) and the median progression-free survival (6.5 months vs. 5.8 months, p=0.115). However, there was a significant difference in response rate (62.4% vs. 48.2%, p=0.006). The pre-planned subgroup analyses showed that IP was associated with longer overall survival in male (11.3 months vs. 10.1 months, p=0.036), < 65 years old (12.7 months vs. 11.3 months, p=0.024), and Eastern Cooperative Oncology Group performance status 0/1 (12.4 months vs. 10.9 months, p=0.040) patient groups. The severity of treatment-related adverse events such as grade 3/4 anemia, nausea and diarrhea was more frequent in patients treated with IP.
CONCLUSION
The IP chemotherapy did not significantly improve the survival compared with EP chemotherapy in Korean patients with extensive-disease SCLC.

Keyword

Etoposide; Irinotecan; Cisplatin; Small cell lung carcinoma; Korean

MeSH Terms

Anemia
Arm
Cisplatin*
Diarrhea
Disease Progression
Disease-Free Survival
Drug Therapy
Etoposide*
Humans
Lung Neoplasms
Male
Nausea
Small Cell Lung Carcinoma*
Cisplatin
Etoposide

Figure

  • Fig. 1. Kaplan-Meier curve of overall survival. IP, irinotecan/cisplatin; EP, etoposide/cisplatin; HR, hazard ratio; CI, confidence interval.

  • Fig. 2. Kaplan-Meier curve of progression-free survival. IP, irinotecan/cisplatin; EP, etoposide/cisplatin; HR, hazard ratio; CI, confidence interval.

  • Fig. 3. Standard forest plot of the hazard ratio for overall survival according to the pre-defined subgroups. HR, hazard ratio; CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; IP, irinotecan/cisplatin; EP, etoposide/cisplatin.


Reference

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