Phase I study of bevacizumab added to fluorouracil- and hydroxyurea-based concomitant chemoradiotherapy for poor-prognosis head and neck cancer

Tanguy Y. Seiwert, Daniel J. Haraf, Ezra E.W. Cohen, Kerstin Stenson, Mary Ellyn Witt, Allison Dekker, Masha Kocherginsky, Ralph R. Weichselbaum, Helen X. Chen, Everett E. Vokes

Research output: Contribution to journalArticlepeer-review

126 Scopus citations


Purpose: We conducted a phase I dose escalation study to determine the maximum-tolerated dose (MTD) and dose-limiting toxicity (DLT) of bevacizumab, when added to the standard FHX (fluorouracil [FU], hydroxyurea [HU], radiation) chemoradiotherapy platform in poor-prognosis head and neck cancer (HNC) patients. Patients and Methods: Patients with recurrent, previously radiated or poor-prognosis, treatment-naive HNC were eligible. Treatment was repeated every 14 days for seven cycles: Bevacizumab was escalated 2.5 to 10 mg/kg, FU 600 to 800 mg/m2 (120 hours continuous infusion), and hydroxyurea from 500 to 1,000 mg (twice daily for 5 days), starting day 1. At the MTD, the cohort was expanded. Results: Forty-three patients were treated. DLT was reached at level 3 (bevacizumab 5 mg/kg, FU 800 mg/m2, HU 1,000 mg) with two grade 3 transaminase elevations and one grade 4 neutropenia, attributed to the combination of chemotherapy with bevacizumab. For level 4, chemotherapy doses were reduced (FU 600 mg/2, HU 500 mg), and bevacizumab escalation continued to 10 mg/kg. Treatment of six assessable patients resulted in one venous thrombosis; this dose level was expanded to 26 patients. Late complications included five patients with fistula formation (11.6%) and four with ulceration/tissue necrosis (9.3%). Serious toxicities (hemorrhage/ thrombosis/death) were comparable to prior reirradiation reports. Median overall survival for reirradiated patients with recurrent, nonmetastatic disease was 10.3 months [95% CI, 5.6 to 13.5]; 2-year cumulative incidence of death resulting from disease was 51.7% (95% CI, 31.7 to 68.5). Conclusion: Bevacizumab can be integrated with FHX chemoradiotherapy at a dose of 10 mg/m2 every 2 weeks with decreased chemotherapy doses because of neutropenia. The regimen shows antitumor activity. Observed fistula formation/tissue necrosis may be bevacizumab related, and further investigation should proceed with careful monitoring.

Original languageEnglish (US)
Pages (from-to)1732-1741
Number of pages10
JournalJournal of Clinical Oncology
Issue number10
StatePublished - 2008
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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