A phase I trial of carboplatin and etoposide for elderly (>or=75 year-old) patients with small-cell lung cancer

Cancer Chemother Pharmacol. 2006 Nov;58(5):601-6. doi: 10.1007/s00280-006-0188-7. Epub 2006 Feb 4.

Abstract

Purpose: The combination of carboplatin and etoposide is currently considered the most appropriate regimen for treating elderly patients with small-cell lung cancer (SCLC). Previous reports on elderly patients, 70 years or older, found that the recommended dose was close to that of younger patients. Then, we conducted a phase I study of carboplatin and etoposide in elderly patients, 75 years or older, with SCLC. This study aimed to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT).

Methods: Twenty-six patients fulfilling the eligibility criteria, chemotherapy-naive, performance status (PS) of 0-2, age>or=75, and adequate organ functions were enrolled. Patients' characteristics were: male/female=21/5; PS 0/1/2=9/11/6; median age (range)=78 (75-82); and limited/extensive stage=16/10. The patients intravenously received carboplatin with a target AUC of 4 or 5 mg min/ml (Chatelut formula) on day 1 and etoposide at 80-120 mg/m2 on days 1, 2 and 3. Therapy was repeated four times in every 4 weeks.

Results: The MTD of carboplatin/etoposide was AUC=5/80, 4/110, and 4/120. The DLTs were thrombocytopenia, neutropenia, leukopenia, and febrile neutropenia. Overall, grade 4 thrombocytopenia, neutropenia (>or=4 days), leukopenia (>or=4 days), and febrile neutropenia occurred in 27, 20, 7, and 13% of cases at MTD levels, respectively, and 0% at other levels. Twenty of 26 patients showed objective responses (2CR, 18PR; RR=77%).

Conclusion: A dose of carboplatin of AUC=4 and etoposide of 100 mg/m2 was recommended in this regimen.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Area Under Curve
  • Carboplatin / administration & dosage
  • Carboplatin / adverse effects
  • Carcinoma, Small Cell / drug therapy*
  • Creatinine / blood
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Eruptions / etiology
  • Etoposide / administration & dosage
  • Etoposide / adverse effects
  • Female
  • Gastrointestinal Tract / drug effects
  • Gastrointestinal Tract / physiopathology
  • Humans
  • Injections, Intravenous
  • Liver Function Tests
  • Lung Neoplasms / drug therapy*
  • Male
  • Nausea / chemically induced
  • Neutropenia / chemically induced
  • Survival Analysis
  • Thrombocytopenia / chemically induced
  • Treatment Outcome
  • Vomiting / chemically induced

Substances

  • Etoposide
  • Creatinine
  • Carboplatin