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


CONCLUSIONS
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.
Drug Development Unit, The Royal Marsden NHS Foundation Trust, Sutton SM2 5PT, UK.|Gastrointestinal Unit, The Royal Marsden NHS Foundation Trust, Sutton SM2 5PT, UK.
Khurum
K
Khan
Drug Development Unit, The Royal Marsden NHS Foundation Trust, Sutton SM2 5PT, UK.|Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton SM2 5NG, UK.|Division of Clinical Studies, The Institute of Cancer Research, Sutton SM2 5NG, UK.
Joo Ern
JE
Ang
Drug Development Unit, The Royal Marsden NHS Foundation Trust, Sutton SM2 5PT, UK.|Gastrointestinal Unit, The Royal Marsden NHS Foundation Trust, Sutton SM2 5PT, UK.
Naureen
N
Starling
Gastrointestinal Unit, The Royal Marsden NHS Foundation Trust, Sutton SM2 5PT, UK.
Francesco
F
Sclafani
Drug Development Unit, The Royal Marsden NHS Foundation Trust, Sutton SM2 5PT, UK.
Krunal
K
Shah
Drug Development Unit, The Royal Marsden NHS Foundation Trust, Sutton SM2 5PT, UK.
Ian
I
Judson
Drug Development Unit, The Royal Marsden NHS Foundation Trust, Sutton SM2 5PT, UK.|Division of Clinical Studies, The Institute of Cancer Research, Sutton SM2 5NG, UK.
L Rhoda
LR
Molife
Drug Development Unit, The Royal Marsden NHS Foundation Trust, Sutton SM2 5PT, UK.|Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton SM2 5NG, UK.|Division of Clinical Studies, The Institute of Cancer Research, Sutton SM2 5NG, UK.
Udai
U
Banerji
Drug Development Unit, The Royal Marsden NHS Foundation Trust, Sutton SM2 5PT, UK.|Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton SM2 5NG, UK.|Division of Clinical Studies, The Institute of Cancer Research, Sutton SM2 5NG, UK.
Johann S
JS
de Bono
Gastrointestinal Unit, The Royal Marsden NHS Foundation Trust, Sutton SM2 5PT, UK.
David
D
Cunningham
Drug Development Unit, The Royal Marsden NHS Foundation Trust, Sutton SM2 5PT, UK.|Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton SM2 5NG, UK.|Division of Clinical Studies, The Institute of Cancer Research, Sutton SM2 5NG, UK.
Stan B
SB
Kaye
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult