Maintenance chemotherapy in small-cell lung cancer: long-term results of a randomized trial. European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group

J Clin Oncol. 1993 Jul;11(7):1230-40. doi: 10.1200/JCO.1993.11.7.1230.

Abstract

Purpose: The present study investigates the role of short chemotherapy (five cycles) versus prolonged (12 cycles) chemotherapy in small-cell lung cancer (SCLC).

Patients and methods: Six hundred eighty-seven patients with SCLC were registered in a multicenter study to receive five cycles of chemotherapy consisting of cyclophosphamide 1 g/m2 on day 1, doxorubicin 45 mg/m2 on day 1, and etoposide 100 mg/m2 on days 1, 3 and 5 (CDE), every 3 weeks. Four hundred thirty-four nonprogressing patients after five cycles of chemotherapy were randomized either to receive seven further cycles of the same chemotherapy or to follow-up.

Results: The response rate of 585 assessable patients was 79%, with 36% attaining a complete response. Toxicity was mainly hematologic, with 16 toxic deaths (2.4% of all eligible patients), 13 of which were due to sepsis. Median survival time from registration of all patients was 326 days (396 and 267 days for limited and extensive disease, respectively) with 3.2% of patients alive at 5 years. No difference in survival between the two arms was observed, with the same number of 5-year survivors in both arms. The patients randomized to the maintenance arm had a progression-free survival (PFS) duration approximately 2 months longer than the patients randomized to follow-up (median of 177 days v 114 days from randomization; P = .0004). Among patients with a partial response who were randomized to receive maintenance chemotherapy, 12 achieved a complete response after 12 cycles. More patients in the follow-up arm than in the maintenance arm received subsequent treatment on progression and responded more frequently to that treatment. Twelve patients developed second malignancies (seven non-small-cell lung cancers).

Conclusion: Prolonged chemotherapy does not offer a better chance of cure than short chemotherapy (five cycles) and does not prolong survival in patients with SCLC. Short, combination chemotherapy appears to be a reasonable choice for standard treatment of SCLC and for attempts to improve the cure rate of this disease.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Small Cell / drug therapy*
  • Cyclophosphamide / administration & dosage
  • Doxorubicin / administration & dosage
  • Drug Administration Schedule
  • Etoposide / administration & dosage
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Male
  • Middle Aged
  • Regression Analysis
  • Survival Analysis
  • Treatment Outcome

Substances

  • Etoposide
  • Doxorubicin
  • Cyclophosphamide

Supplementary concepts

  • ACE protocol 1