Capecitabine and streptozocin ± cisplatin in advanced gastroenteropancreatic neuroendocrine tumours.
BACKGROUND
Cytotoxic chemotherapy is widely used for advanced, unresectable pancreatic and other gastrointestinal foregut neuroendocrine tumours (NETs) and the most commonly used regimen combines 5-fluorouracil with streptozocin. The NET01 trial was designed to investigate whether capecitabine combined with streptozocin was an acceptable regimen with or without adding cisplatin.


METHODS
Patients with advanced, unresectable NETs of pancreatic, gastrointestinal foregut or unknown primary site were randomised to receive three-weekly capecitabine (Cap) 625 mg/m(2) twice daily orally, streptozocin (Strep) 1.0 g/m(2) intravenously on day 1, with or without cisplatin (Cis) 70 mg/m(2) intravenously on day 1. The primary outcome measure was objective response. Secondary outcome measures included progression-free and overall survival, quality of life, toxicity and biochemical response.


RESULTS
86 (44 CapStrep, 42 CapStrepCis) patients were randomised. Best objective response rate was 12% (95% confidence interval (CI)=2-22%) with CapStrep and 16% (95% CI=4-27.4%) with CapStrepCis. Disease-control rate was 80% with CapStrep and 74% with CapStrepCis. The estimated median progression-free and overall survival were 10.2 and 26.7 months for CapStrep and 9.7 and 27.5 months for CapStrepCis. 44% of CapStrep and 68% of CapStrepCis patients experienced grade ≥3 adverse events.


CONCLUSIONS
The efficacies of the novel CapStrep±Cis regimens were very similar. CapStrep was better tolerated than CapStrepCis. The trial was registered as EudraCT: 2004-005202-71 and ISRCTN: 35124268.
Neuroendocrine Tumour Unit, The Royal Free Hospital, Pond Street, London, UK; UCL Cancer Institute, London, UK.
Tim
T
Meyer
Cambridge Cancer Trials Centre, Cambridge Clinical Trials Unit - Cancer Theme, Addenbrooke's Hospital, Cambridge, UK; Medical Research Council Biostatistics Unit Hub for Trials Methodology, Cambridge, UK.
Wendi
W
Qian
Neuroendocrine Tumour Unit, The Royal Free Hospital, Pond Street, London, UK.
Martyn E
ME
Caplin
Cambridge Cancer Trials Centre, Cambridge Clinical Trials Unit - Cancer Theme, Addenbrooke's Hospital, Cambridge, UK.
Graham
G
Armstrong
Cambridge Cancer Trials Centre, Cambridge Clinical Trials Unit - Cancer Theme, Addenbrooke's Hospital, Cambridge, UK.
Si-Houy
SH
Lao-Sirieix
Cambridge Cancer Trials Centre, Cambridge Clinical Trials Unit - Cancer Theme, Addenbrooke's Hospital, Cambridge, UK.
Richard
R
Hardy
Department of Medical Oncology, The Christie, Manchester, UK.
Juan W
JW
Valle
Oxford Neuroendocrine Tumour Centre, Churchill Hospital, Oxford, UK.
Denis C
DC
Talbot
Gastrointestinal Unit, The Royal Marsden, London, UK.
David
D
Cunningham
Beatson Oncology Centre, Glasgow, UK.
Nick
N
Reed
Oncology Centre, Addenbrooke's Hospital, Cambridge, UK.
Ashley
A
Shaw
Neuroendocrine Tumour Unit, The Royal Free Hospital, Pond Street, London, UK.
Shaunak
S
Navalkissoor
Neuroendocrine Tumour Unit, The Royal Free Hospital, Pond Street, London, UK.
Tu-Vinh
TV
Luong
Cambridge Cancer Trials Centre, Cambridge Clinical Trials Unit - Cancer Theme, Addenbrooke's Hospital, Cambridge, UK; Oncology Centre, Addenbrooke's Hospital, Cambridge, UK. Electronic address: pippa.corrie@addenbrookes.nhs.uk.
Pippa G
PG
Corrie
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000069287:Capecitabine; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D003967:Diarrhea / Q000139:chemically induced; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000188:drug therapy*; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D011788:Quality of Life; D013311:Streptozocin / Q000008:administration & dosage / Q000009:adverse effects; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
D003841:Deoxycytidine; D013311:Streptozocin; D000069287:Capecitabine; D002945:Cisplatin; D005472:Fluorouracil
Capecitabine; Chemotherapy; Cisplatin; Neuroendocrine tumour; Phase II; Randomised clinical trial; Streptozocin