Epirubicin, cisplatin and oral UFT with leucovorin ('ECU'): a phase I-II study in patients with advanced upper gastrointestinal tract cancer.
BACKGROUND
ECF (epirubicin, cisplatin, protracted venous fluorouracil) is superior to FAMTX in gastroesophageal cancer, but protracted fluorouracil adds to its morbidity and cost. In this dose-escalation pilot study, fluorouracil was replaced by oral UFT and leucovorin.


METHODS
Thirty unpretreated patients with advanced upper gastrointestinal cancers received epirubicin 50 mg/m2 and cisplatin 60 mg/m2 i.v. on day 1, and leucovorin 45 mg p.o. on days 1, 8 and 15, of a 21-day cycle for up to 8 cycles. UFT was taken 12-hourly throughout, at escalating doses in four cohorts ranging from 150-325 mg/m2 per day.


RESULTS
The maximum tolerable dose of UFT, recommended for further study, was 200 mg/m2 per day. At higher doses, more than two-thirds patients required dose reductions, although mostly for persistent mild (CTC grade 2) nausea, diarrhoea or fatigue, rather than for severe acute toxicity. Myelotoxicity was mild. Twenty patients, including 15 with gastroesophageal cancer, had assessable disease. Among these there were nine WHO objective responses, all in gastroesophageal patients, including two radiological complete responses.


CONCLUSIONS
ECU is well tolerated at the defined dose, with activity comparable to ECF in gastroesophageal cancer. UFT and other oral 5FU dosing strategies make promising components of combination chemotherapy, deserving further, randomised evaluation.
Seymour
M T
MT
ICRF Cancer Medicine Research Unit, Cookridge Hospital, Leeds, UK. M.Seymour@icrf.icent.uk
Dent
J T
JT
Papamichael
D
D
Wilson
G
G
Cresswell
H
H
Slevin
M L
ML
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010865:Pilot Projects; D012720:Severity of Illness Index; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D005641:Tegafur / Q000008:administration & dosage; D016896:Treatment Outcome; D006113:United Kingdom
D000903:Antibiotics, Antineoplastic; D005641:Tegafur; D002945:Cisplatin; D002955:Leucovorin