Cisplatin plus etoposide with and without ifosfamide in extensive small-cell lung cancer: a Hoosier Oncology Group study

J Clin Oncol. 1995 Oct;13(10):2594-9. doi: 10.1200/JCO.1995.13.10.2594.


Purpose: To determine whether the addition of ifosfamide to cisplatin plus etoposide improves the response rate, time to disease progression, or overall survival in previously untreated patients with extensive-stage small-cell carcinoma of the lung (SCLC).

Patients and methods: Patients with extensive SCLC with a Karnofsky performance score (KPS) > or = 50 and adequate renal function and bone marrow reserve were eligible. Patients with CNS metastases were eligible and received concurrent whole-brain radiotherapy. Patients were randomized to receive cisplatin (20 mg/m2) plus etoposide (100 mg/m2) (VP) both given intravenously (i.v.) on days 1 to 4 or cisplatin (20 mg/m2), ifosfamide (1.2 g/m2), and etoposide (75 mg/m2) (VIP) all given i.v. on days 1 to 4. Cycles were repeated every 3 weeks for four cycles.

Results: From May 1989 through March 1993, 171 patients were randomized (84 to VP and 87 to VIP). The median follow-up duration is 26 months. All patients were assessable for survival; 163 were fully assessable for response and 162 for toxicity. Myelosuppression was greater with VIP. Objective responses were observed in 55 of 82 (67%) and 59 of 81 (73%) assessable patients treated with VP and VIP, respectively (difference not significant). The difference in the median time to progression was statistically different (P = .039). The median survival times on VP and VIP were 7.3 months and 9.0 months, respectively (P = .045 for survival curves by stratified log-rank test) with 2-year survival rates of 5% versus 13%, respectively.

Conclusion: VIP combination chemotherapy is associated with an improved time to progression and overall survival over VP therapy in patients with extensive SCLC.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Brain Neoplasms / diagnostic imaging
  • Brain Neoplasms / secondary
  • Carcinoma, Small Cell / drug therapy*
  • Carcinoma, Small Cell / mortality
  • Carcinoma, Small Cell / radiotherapy
  • Carcinoma, Small Cell / secondary
  • Cisplatin / administration & dosage
  • Combined Modality Therapy
  • Cranial Irradiation
  • Disease-Free Survival
  • Etoposide / administration & dosage
  • Female
  • Follow-Up Studies
  • Humans
  • Ifosfamide / administration & dosage
  • Injections, Intravenous
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / radiotherapy
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Radiography
  • Regression Analysis
  • Survival Rate


  • Etoposide
  • Cisplatin
  • Ifosfamide