Phase II trials of imatinib mesylate and docetaxel in patients with metastatic non-small cell lung cancer and head and neck squamous cell carcinoma

Anne S. Tsao, Suyu Liu, Junya Fujimoto, Ignacio I. Wistuba, J. Jack Lee, Edith M. Marom, Chusilp Charnsangavej, Frank V. Fossella, Hai T. Tran, George R. Blumenschein, Vassiliki Papadimitrakopoulou, Merrill S. Kies, Waun K. Hong, David J. Stewart

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: Two phase II clinical trials in the aerodigestive tumors were undertaken to evaluate the efficacy of imatinib mesylate-docetaxel. We hypothesized that imatinib mesylate would inhibit platelet-derived growth factor receptor (PDGFR) on pericytes and increase docetaxel uptake into tumor cells for an additive antitumor effect. Baseline tumor specimens, serum, and perfusion computed tomography (CT) scans were obtained for supportive evaluation. MATERIALS AND Methods: Eligible patients with metastatic non-small cell lung cancer (NSCLC) treated with 1 prior therapy and chemonaive patients with head and neck squamous cell carcinoma (HNSCC) were enrolled in separate trials, which administered both docetaxel (60 mg/m every 3 weeks) and oral imatinib mesylate (400 mg daily). Both trials used interim analyses for efficacy and safety. Results: Twenty-two patients with NSCLC and seven patients with HNSCC were enrolled. Both trials were closed early due to lack of efficacy, significant toxicity, and a potential antagonistic effect. In the NSCLC study, the response rate was 4.5%, median progression-free survival (PFS) 7.9 weeks, and overall survival 35.6 weeks. The HNSCC trial yielded a response rate 0%, PFS 8.8 weeks, and overall survival 34.7 weeks. Baseline NSCLC tumor immunohistochemical biomarker analyses indicated that lower expression of stromal PDGFRβ correlated with a better PFS, whereas stromal PDGFRα and tumor cell PDGFRβ were associated with a worse clinical outcome when treated with imatinib mesylate-docetaxel. Conclusion: We do not recommend further investigation of this regimen in the aerodigestive tumors. Future investigations in PDGFR tyrosine kinase inhibitors should be used with caution in combination with taxanes and validation of the potential predictive or prognostic biomarkers stromal PDGFRα/β, and tumor cell PDGFRβ are needed.

Original languageEnglish
Pages (from-to)2104-2111
Number of pages8
JournalJournal of Thoracic Oncology
Volume6
Issue number12
DOIs
StatePublished - Dec 2011
Externally publishedYes

Keywords

  • Docetaxel
  • Head and neck squamous cell carcinoma
  • Imatinib mesylate
  • Non-small cell lung cancer

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