A randomized phase II trial of echinomycin, trimetrexate, and cisplatin plus etoposide in patients with metastatic nonsmall cell lung carcinoma: An Eastern Cooperative Oncology Group study (E1587)

Alex Y. Chang, Kyung Mann Kim, Hélène Boucher, Philip Bonomi, James A. Stewart, Daniel D. Karp, Ronald H. Blum

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND. Patients with metastatic nonsmall cell lung carcinoma (NSCLC) usually have a poor prognosis. A chemotherapy regimen containing cisplatin is commonly used for symptom palliation. Echinomycin is a potent bifunctional intercalator of double-strand DNA; trimetrexate is a new derivative of methotrexate and is active against methotrexate-resistant tumor cells in vitro. METHODS. The Eastern Cooperative Oncology Group conducted a randomized Phase II study. Eligible patients were assigned to receive echinomycin 1200 μg/m2 by intravenous (i.v.) infusion over 30-60 minutes once a week for 4 weeks, repeated every 6 weeks; trimetrexate 12 mg/m2 i.v. bolus on Days 1-5 every 3 weeks, or 8 mg/m2 i.v. bolus on Days 1-5 for patients who had prior radiation to greater than 30% of their bone marrow; or cisplatin 60 mg/m2 i.v. on Day 1 and etoposide 120 mg/m2 i.v. on Days 1-3 every 4 weeks. Patients were evaluated before each cycle for tumor response, toxicity, and quality-of-life measurements. RESULTS. One hundred thirty-six patients were entered on the study, and 118 were evaluable for toxicity and response. The response rates were 16%, 5%, and 5% in patients treated with cisplatin and etoposide, echinomycin, and trimetrexate, respectively. There were no complete responses. The median survival was 37.9, 24.3, and 28.0 weeks for patients who received cisplatin and etoposide, echinomycin, and trimetrexate, respectively. Although cisplatin and etoposide appeared to give better therapeutic results, the response rate or survival did not reach statistical significance. This may have been due to inadequate sample size. Neither did quality-of-life measurement show any significant differences among treatments. CONCLUSIONS. Echinomycin and trimetrexate had minimal antitumor activity in patients with metastatic NSCLC. Response rate and survival remained poor in all three treatment arms. Patients should be encouraged to participate in clinical trials so that more effective therapy can be identified.

Original languageEnglish (US)
Pages (from-to)292-300
Number of pages9
JournalCancer
Volume82
Issue number2
DOIs
StatePublished - Jan 15 1998
Externally publishedYes

Keywords

  • Chemotherapy
  • Cisplatin
  • Echinomycin
  • Etoposide
  • Nonsmall cell lung carcinoma
  • Trimetrexate

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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