Phase I trials in patients with relapsed, advanced upper gastrointestinal carcinomas: experience in a specialist unit

Abstract

Background: Conventional therapeutic options for patients with advanced upper gastrointestinal cancers (UGIC) are limited. Following first-line treatments, some patients are offered experimental therapies, including participation in Phase I trials. This study aims to describe the experience of UGIC patients treated in a dedicated Phase I unit. Methods: Patient, tumour and treatment characteristics, and clinical outcomes of UGIC patients treated consecutively at the Drug Development Unit, Royal Marsden Hospital, between 2005 and 2009, were recorded. Results: Ninety-six patients who previously received a median of 2 (range 1–4) lines of chemotherapies were treated in 30 Phase I trials. Of 81 evaluable patients, 9 achieved RECIST-objective response (11 %) with a 6-month clinical benefit rate of 14 %. Median progression free and overall survival were 7.7 weeks [95 %CI 7.7 (6.4–9.0)] and 19.1 weeks (95 %CI 17.5–20.8), respectively. Grade 3 or 4 toxicities were observed in 37 patients (39 %) and led to trial discontinuation in 9 (9 %); no toxicity-related death was recorded. In the multivariate analysis, serum albumin (<35 g/dl, HR2.0, p = 0.002) and lactate dehydrogenase (>192 μmol/l, HR1.7, p = 0.016) were prognostic of overall survival. Conclusion: Phase I clinical trials can be considered a reasonable option in selected patients with relapsed UGIC. The use of objective prognosticators may improve selection and risk/benefit profile of patients.