Assessing the ability of the antiangiogenic and anticytokine agent thalidomide to modulate radiation-induced lung injury

Mitchell S. Anscher, Jennifer Garst, Lawrence B. Marks, Nicole Larrier, Frank Dunphy, James E. Herndon, Robert Clough, Christine Marino, Zeljko Vujaskovic, Sumin Zhou, Mark W. Dewhirst, Timothy D. Shafman, Jeffrey Crawford

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Purpose: Thalidomide has broad anticytokine properties, which might protect normal tissues in patients undergoing chemoradiotherapy. The purpose of this study was to determine the maximal tolerated dose of thalidomide when used in combination with vinorelbine plus thoracic radiotherapy. Methods and Materials: Eligible patients had inoperable Stage III non-small-cell lung cancer, a Karnofsky Performance Status ≥70, and life expectancy ≥6 months. Patients underwent pretreatment evaluation of lung function. Radiotherapy consisted of 66 Gy in 6.5 weeks. Vinorelbine was administered i.v. (5 mg/m2) 3 times per week just before radiotherapy. Thalidomide was begun at 50 mg, p.o., on day 1 of chemoradiotherapy and continued once daily for 6 months. Side effects were scored using National Cancer Institute Common Toxicity Criteria. Results: Ten patients were enrolled. Of the first 6 patients, 2 developed major thrombotic events that were believed to be possibly related to thalidomide. The study was suspended and modified to require prophylactic anticoagulation. Of the last 4 patients, 2 developed dose-limiting toxicity attributable to thalidomide; both patients required a dose reduction of thalidomide to <50 mg/day. Because the drug is not available in an oral product providing <50 mg/day, the study was closed. Conclusions: The combination of thalidomide concurrently with thoracic radiotherapy and vinorelbine resulted in excessive toxicity.

Original languageEnglish (US)
Pages (from-to)477-482
Number of pages6
JournalInternational Journal of Radiation Oncology Biology Physics
Volume66
Issue number2
DOIs
Publication statusPublished - Oct 1 2006

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Keywords

  • Complications
  • Cytokines
  • Non-small-cell lung cancer
  • Thalidomide

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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