A phase I and II trial of epirubicin, cisplatin, 24-hour infusion 5 fluorouracil and sodium folinate in patients with advanced esophagogastric carcinomas.
OBJECTIVE
Advanced esophagogastric carcinoma has a poor prognosis. Palliative chemotherapy provides a survival advantage and improved quality of life. Epirubicin, cisplatin and continuous infusional 5-fluorouracil (5-FU) (ECF) is a well-established chemotherapy regimen but a continuous chemotherapy infusion is not always feasible or acceptable.


METHODS
We conducted a phase I and II trial of a modified version of ECF, utilizing 5-FU as a 24-h infusion on day 1 and day 8 of a 21-day cycle, administered with sodium folinate as a modulator of 5-FU (ECSF). In the phase I study the dose of 5-FU was increased in successive cohorts from 1250 mg/m(2) , 1500 mg/m(2) , and 1750 mg/m(2) to 2000 mg/m(2) per 24 h.


RESULTS
Dose limiting toxicity of febrile neutropenia was encountered at 2000 mg/m. The recommended dose for 5-FU was 1750 mg/m(2) . Overall 29 patients were treated with ECSF of whom 27 were evaluable for toxicity. The response rate was 45% on an intention-to-treat analysis with a complete response rate of 3%. The median response rate was 4.1 months and the median survival was 10.7 months. A total of 23 patients (72%) obtained clinical benefit with improvement in dysphagia or weight gain. central venous catheter (CVC) complications were observed in 12 (41%) patients.


CONCLUSIONS
ECSF was associated with a response rate and survival similar to that reported with standard ECF. ECSF may provide an alternative regimen to standard ECF when a continuous ambulatory infusion pump is not feasible or not preferred by the patient. CVC complications are a limitation.
Department of Medical Oncology, Guy's Hospital, London, UK. c.karapetis@flinders.edu.au
Christos S
CS
Karapetis
Kerry A
KA
Cheong
Desmond
D
Yip
Andrew H
AH
Strickland
Christopher
C
Steer
Gavin
G
Marx
Sonia
S
Yip
Kathryn
K
Chrystal
Peter G
PG
Harper
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D015251:Epirubicin / Q000008:administration & dosage; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D016896:Treatment Outcome; D014803:Vitamin B Complex / Q000627:therapeutic use*
D014803:Vitamin B Complex; D015251:Epirubicin; D002945:Cisplatin; D002955:Leucovorin