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

Abstract

5561 Background: At University of Chicago, concomitant chemoRT for advanced and recurrent head and neck cancer has been studied for 2 decades. We investigated the addition of CPT-11 as a promising new agent to our established regimen of 5-FU, hydroxyurea (HU), and hyperfractionated RT (HF2X). The goal was to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of this regimen. Time to progression, patterns of failure, and survival were secondary endpoints. Methods: Between 8/98 and 8/01, 31 pts with advanced and recurrent H&N cancer were enrolled. Previously untreated pts were eligible if unressectable or had an expected 2 year survival <20%. Pts with metastatic disease were included if local radiotherapy to the H&N was required. 19 previously radiated pts were included. The median prior RT dose was 66.4 Gy (range: 45–88.4 Gy). The starting dose of CPT-11 was 5 mg/m2/d delivered with continuous infusion 5-FU (600 mg/m2/d), HU (500 mg PO q 12 hours) and BID RT (1.5 Gy/fraction). All pts were treated on a 14 d cycle with 5 consecutive days of therapy and a 9 day break. Subsequent cohorts had CPT-11 escalated by 5 mg/m2/d. Subsequently, 14 pts were treated at the MTD. Results: CPT-11 was well tolerated at the 5 mg/m2/d and 10 mg/m2/d dose levels. 3/3 pts treated at the 15 mg/m2/d level, experienced neutropenic DLT during cycles 1–2. 8/18 (44%) evaluable pts had a response; 5 (28%) had a CR, 3 (17%) had a PR, 5 had stable disease (28%) and 5 pts progressed. At a median f/u of 24 mos for surviving pts, (range, 16.5–51), 4 pts (13%) are alive and NED. 2 yr overall survival (OS) and disease free survival (DFS) was 31.3% and 24.4%. Re-irradiated pts had a median survival of 9.5 mos (range: 0.7–50.5) and a 2 yr OS of 24.5%. 2 yr DFS of squamous histology re-irradiation pts was 23%. Conclusions: The MTD and recommended phase II dose of CPT-11/ HF2X was 10 mg/m2/d. Neutropenia was dose limiting. Response rates were reasonable. Further investigation of this regimen may be worth additional study. Re-irradiation with concurrent chemotherapy resulted in the survival of a significant fraction of pts. No significant financial relationships to disclose.