Background: Phase I trials seek to determine the maximum-tolerated drug dose that will be used in future efficacy studies and are often criticized for their inability to clinically benefit patients. This study examined whether time to progression (TTP) in patients with head and neck cancer enrolled in phase I trials at M. D. Anderson Cancer Center was inferior to TTP with last FDA-approved drug prior to inclusion in the phase I trial. We also examined the molecular profile of these patients including: PI3CA mutations and PTEN deletions

Methods: We retrospectively reviewed medical chart data from head and neck cancer patients enrolled in phase I trials at M. D. Anderson, including age, gender, performance status, tumor histology, hemoglobin, LDH, albumin, platelets, clinical response and TTP while on phase I trials and TTP to their last FDA-approved therapy prior to inclusion on phase I. We conducted univariate and multivariate analysis using SPSSv17.

Results: 62 patients with head and neck cancer were enrolled in phase I trials from 2003 to 2009. Of these, 39 (63%) had squamous head and neck cancers, 12 (19%) had adenocystic carcinomas, and 4 (6%) had oropharyngeal adenocarcinomas. Median age was 54.2 years (range 26-80); 52 (83%) were male. 58 patients had an ECOG performance status of 0-1. Median and standard deviation values of hemoglobin, LDH, albumin and platelets were: 12.5 (1.8) g/dL, 689 (772), 4.02 (0.43) g/dL and 299 (113.96), respectively. Univariate survival analysis results showed that a hemoglobin level of ≤10.5 g/dL, LDH ≤700 and partial response (PR) or stable disease (SD) on phase I trials were associated with survival (p<0.0009). Only a hemoglobin level ≤10.5g/dL (p=0.0009) and PR/SD to phase I trial (p=0.001) were associated with increased survival in multivariate analyses. Last treatment line prior to inclusion in phase I trials was based on FDA-approved drug in 59 patients. 12 (20%) were enrolled in trials including cytotoxic agents and 47 (80%) were treated with targeted therapies. For these 59 patients we conducted Kaplan-Meier and found that TTP to phase I drugs was not inferior to TTP with last FDA-approved drug (12 vs. 11 weeks, log-rank p=0.814). One of these patients was found to have a PTEN deletion on her tumor and had a remarkable response (70% decrease by RECIST criteria) when treated on a phase I trial with an mTOR inhibitor. We will be presenting the molecular profile and correlation with response for all these patients.

Conclusion: We show that clinical outcome for patients with head and neck cancers treated in phase I trials is not inferior to outcome with last treatment line based on a FDA-approved drug. We will be also presenting data regarding the molecular profile of these patients including PI3CA mutations and PTEN deletions and correlation with response to trials including drugs targeting mTOR/PI3K pathway.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2773.