Investigational New Drugs

, Volume 28, Issue 5, pp 677–683

Phase II study of sunitinib malate in head and neck squamous cell carcinoma

  • Nicholas W. Choong
  • Mark Kozloff
  • David Taber
  • H. Shawn Hu
  • James WadeIII
  • Percy Ivy
  • Theodore G. Karrison
  • Allison Dekker
  • Everett E. Vokes
  • Ezra E. W. Cohen
PHASE II STUDIES

Summary

Background Sunitinib is an orally administered multitargeted tyrosine kinase inhibitor of RET, VEGFR, PDGFR, and c-KIT. We conducted a phase II trial to evaluate the tolerability and efficacy of sunitinib in metastatic and/or recurrent SCCHN patients. Methods Patients who had received no more than two prior chemotherapy regimens were eligible and, depending on ECOG performance status (PS), were entered into either Cohort A (PS 0-1) or Cohort B (PS 2). Sunitinib was administered in 6-week cycles at 50 mg daily for 4 weeks followed by 2 weeks off. Primary endpoint for Cohort A was objective tumor response. A Simon two-stage design required twelve patients to be enrolled in the first stage and if 1 or fewer responses were observed, further study of this cohort would be terminated due to lack of treatment efficacy. Primary endpoint of Cohort B was to determine the feasibility of sunitinib in patients with ECOG performance status 2. Results Twenty-two patients were accrued (Cohort A — 15 patients, Cohort B — 7 patients). Median age in cohort A and B was 56 and 61 years, respectively. Grade 3 hematologic toxicities encountered were lymphopenia (18%), neutropenia (14%) and thrombocytopenia (5%). There was only one incidence of grade 4 hematologic toxicity which was thrombocytopenia. Fatigue and anorexia were the most common non-hematologic toxicities. Grade 3 fatigue occurred in 23% of patients. The only grade 4 non-hematologic toxicity was one incidence of gastrointestinal hemorrhage. Non-fatal hemorrhagic complications occurred in 8 patients: epistaxis (3 patients), pulmonary hemorrhage (2 patients), gastrointestinal hemorrhage (2 patients) and tumor hemorrhage (1 patient). Four patients were not evaluable for tumor response (Cohort A — 3patients, Cohort B — 1 pt). One partial response was observed in the entire study. Dose reduction was required in 5 patients (Cohort A — 3 patients for grd 3 fatigue, grd 3 mucositis and recurrent grd 3 neutropenia; Cohort B — 2 patients for grd 3 fatigue and grd 3 nausea). Median time to progression for cohort A and B were 8.4 and 10.5 weeks, respectively. Median overall survival for cohort A and B was 21 and 19 weeks, respectively. Conclusions Sunitinib had low single agent activity in SCCHN necessitating early closure of cohort A at interim analysis. Sunitinib was well tolerated in PS 2 patients. Further evaluation of single agent sunitinib in head and neck is not supported by the results of this trial.

Keywords

Head and neck cancer Squamous cell carcinoma Chemotherapy Sunitinib Multitargeted tyrosine kinase inhibitor 

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Nicholas W. Choong
    • 1
    • 2
  • Mark Kozloff
    • 3
  • David Taber
    • 4
  • H. Shawn Hu
    • 5
  • James WadeIII
    • 6
  • Percy Ivy
    • 7
  • Theodore G. Karrison
    • 8
  • Allison Dekker
    • 1
  • Everett E. Vokes
    • 1
    • 9
  • Ezra E. W. Cohen
    • 1
    • 9
  1. 1.Section of Hematology-Oncology and Phase II networkUniversity of Chicago Medical CenterChicagoUSA
  2. 2.Division of Neoplastic DiseasesMedical College of WisconsinMilwaukeeUSA
  3. 3.Ingalls HospitalHarveyUSA
  4. 4.Michiana Hematology OncologySouth BendUSA
  5. 5.David C. Pratt Cancer CenterSt. LouisUSA
  6. 6.Cancer Care SpecialistsDecaturUSA
  7. 7.Investigational Drug Branch, Cancer Therapy Evaluation Program, Division of Cancer Treatments and DiagnosisNational Cancer InstituteRockvilleUSA
  8. 8.Department of Health StudiesUniversity of ChicagoChicagoUSA
  9. 9.University of Chicago Cancer Research CenterChicagoUSA

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