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.
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.
Authors: S Boeck; K Weigang-Köhler; M Fuchs; E Kettner; D Quietzsch; J Trojan; O Stötzer; S Zeuzem; F Lordick; C-H Köhne; H Kröning; T Steinmetz; H Depenbrock; V Heinemann Journal: Ann Oncol Date: 2007-01-17 Impact factor: 32.976
Authors: David Cunningham; William H Allum; Sally P Stenning; Jeremy N Thompson; Cornelis J H Van de Velde; Marianne Nicolson; J Howard Scarffe; Fiona J Lofts; Stephen J Falk; Timothy J Iveson; David B Smith; Ruth E Langley; Monica Verma; Simon Weeden; Yu Jo Chua Journal: N Engl J Med Date: 2006-07-06 Impact factor: 91.245
Authors: H Ulrich-Pur; M Raderer; G Verena Kornek; B Schüll; K Schmid; K Haider; W Kwasny; D Depisch; B Schneeweiss; F Lang; W Scheithauer Journal: Br J Cancer Date: 2003-04-22 Impact factor: 7.640
Authors: K H Khan; T A Yap; A Ring; L R Molife; S Bodla; K Thomas; A Zivi; A Smith; I Judson; U Banerji; J S de Bono; S B Kaye Journal: Br J Cancer Date: 2016-01-12 Impact factor: 7.640