title: Phase II trials of imatinib mesylate and docetaxel in patients with metastatic non-small cell lung cancer and head and neck squamous cell carcinoma.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Thoracic/Head & Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA. astsao@mdanderson.org
authors: Anne S
authors: AS
authors: Tsao
authors: Suyu
authors: S
authors: Liu
authors: Junya
authors: J
authors: Fujimoto
authors: Ignacio I
authors: II
authors: Wistuba
authors: J Jack
authors: JJ
authors: Lee
authors: Edith M
authors: EM
authors: Marom
authors: Chusilp
authors: C
authors: Charnsangavej
authors: Frank V
authors: FV
authors: Fossella
authors: Hai T
authors: HT
authors: Tran
authors: George R
authors: GR
authors: Blumenschein
authors: Vassiliki
authors: V
authors: Papadimitrakopoulou
authors: Merrill S
authors: MS
authors: Kies
authors: Waun K
authors: WK
authors: Hong
authors: David J
authors: DJ
authors: Stewart
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000077214:Becaplermin; D001549:Benzamides; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000737:chemistry / Q000188:drug therapy*; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000737:chemistry / Q000188:drug therapy*; D016009:Chi-Square Distribution; D018572:Disease-Free Survival; D000077143:Docetaxel; D057239:Early Termination of Clinical Trials; D005260:Female; D018628:Gene Dosage; D006258:Head and Neck Neoplasms / Q000097:blood / Q000737:chemistry / Q000188:drug therapy*; D006801:Humans; D000068877:Imatinib Mesylate; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000097:blood / Q000737:chemistry / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects; D016016:Proportional Hazards Models; D020574:Proto-Oncogene Proteins c-sis / Q000097:blood; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000032:analysis; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000032:analysis / Q000235:genetics; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D001549:Benzamides; D014408:Biomarkers, Tumor; D010879:Piperazines; D020574:Proto-Oncogene Proteins c-sis; D011743:Pyrimidines; D043823:Taxoids; D000077143:Docetaxel; D000077214:Becaplermin; D000068877:Imatinib Mesylate; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta