A phase II study of all-trans-retinoic acid plus cisplatin and etoposide in patients with extensive stage small cell lung carcinoma: An eastern cooperative oncology group study

Gregory P. Kalemkerian, Michael Jiroutek, David S. Ettinger, John A. Dorighi, David H. Johnson, Mack Mabry

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

BACKGROUND. The dysregulation of both myc gene expression and retinoid signaling pathways commonly occurs in small cell lung carcinoma (SCLC). Because preclinical data showed that all-trans-retinoic acid (RA) inhibited SCLC growth, altered myc expression, and blocked transition to a treatment- resistant phenotype, a Phase II trial was designed to determine the effects of the combination of RA, cisplatin, and etoposide in patients with SCLC. METHODS. Patients with untreated, extensive stage SCLC were treated with up to 8 cycles of cisplatin, 60 mg/m2, intravenously (i.v.) on Day 1 and etoposide, 120 mg/m2, i.v. on Days 1-3 in addition to up to 1 year of oral RA, 150 mg/m2/day. RESULTS. Of 22 assessable patients 1 had a complete response and 9 had a partial response, for an overall response rate of 45% (95% confidence interval, 24-68%). The median survival was 10.9 months and the 1-year survival was 41%. The median duration of chemotherapy was 6 cycles and the median duration of RA treatment was 2.8 months. Thirteen patients discontinued RA prematurely due to toxicity and only 4 responders were receiving RA at the time of recurrence. Toxicity-limiting RA treatment mainly was comprised of mucocutaneous changes and headaches. CONCLUSIONS. RA at a dose of 150 mg/m2/day was tolerated poorly in combination with cisplatin plus etoposide, leading to early discontinuation of RA in the majority of patients. The hematologic toxicity, response rate, and survival were similar to those associated with cisplatin and etoposide in prior trials. Further studies with more active and less toxic agents will be required to determine the role of retinoids in the treatment of SCLC.

Original languageEnglish (US)
Pages (from-to)1102-1108
Number of pages7
JournalCancer
Volume83
Issue number6
DOIs
StatePublished - Sep 15 1998

Keywords

  • All-trans-retinoic acid
  • Cisplatin
  • Combination chemotherapy
  • Etoposide
  • Experimental therapeutics
  • Lung carcinoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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