Phase I study of concomitant chemoradiotherapy with irinotecan, 5-FU, and hydroxyurea for patients with advanced and/or recurrent head and neck cancer.


Journal Article

PURPOSE: We sought to investigate CPT-11 as a promising agent to our established regimen of 5-fluorouracil (5-FU), hydroxyurea, and hyperfractionated radiation therapy. A phase I study was conducted to determine the maximum tolerated dose and dose-limiting toxicities of this regimen. PATIENTS AND METHODS: Eligible patients included patients with poor prognosis advanced head and neck cancer who required radiation therapy. All patients were treated on a 14-day cycle. Each patient received 5-FU (600 mg/m(2)/d), hydroxyurea (500 mg orally every 12 hours), radiation therapy twice daily (150 cGy each fraction), and CPT-11 at a starting dose of 5 mg/m(2)/d for 5 consecutive days followed by a 9-day break. CPT-11 was escalated in five mg/m(2)/d increments. Dose-limiting toxicity was defined as grade 4 hematologic toxicity, persistent grade 4 dermatitis and mucositis, grade 4 diarrhea despite maximal pharmacologic intervention, and inability to receive full-dose chemotherapy with the next cycle of treatment. Fourteen patients were treated at maximum tolerated dose to verify the recommended phase II dose. RESULTS: Between August 1998 and August 2001, 31 patients with advanced and/or recurrent head and neck cancer were enrolled. Cohorts of nine, four, three, and 14 patients were treated at 5-, 10-, 15-, and 10-mg/m(2)/d dose levels of CPT-11. The 5- and 10-mg/m(2)/d dose levels were well tolerated All three patients treated at 15 mg/m(2)/d experienced neutropenic dose-limiting toxicity during cycles 1-2. DISCUSSION: The maximum tolerated dose and recommended phase II dose of CPT-11 with hyperfractionated radiation therapy is 10 mg/m(2)/d.

Full Text

Duke Authors

Cited Authors

  • Salama, JK; Haraf, DJ; Stenson, K; Milano, MT; Witt, ME; Vokes, EE

Published Date

  • March 2005

Published In

Volume / Issue

  • 11 / 2

Start / End Page

  • 140 - 146

PubMed ID

  • 15969989

Pubmed Central ID

  • 15969989

International Standard Serial Number (ISSN)

  • 1528-9117

Digital Object Identifier (DOI)

  • 10.1097/00130404-200503000-00009


  • eng

Conference Location

  • United States