A phase I study of docetaxel, Cisplatin, 5-Fluorouracil and leucovorin.
OBJECTIVE
Cisplatin, 5-fluorouracil (5-FU) and docetaxel are active agents in the treatment of upper gastrointestinal malignancies. This phase I study was undertaken to determine the maximally tolerated dose and dose-limiting toxicities of a combination of these drugs given in an ambulatory setting using a bolus schedule of 5-FU.


METHODS
Twenty patients with gastrointestinal malignancies were treated with docetaxel on day 1, cisplatin on day 2 and bolus 5-FU with leucovorin each day for 5 days, without prophylactic antibiotics or colony-stimulating factors. The cycle was repeated at 21-day intervals. A dose-escalating phase I design was used.


RESULTS
There were two treatment-related deaths as a result of neutropenia and sepsis. The maximally tolerated dose was docetaxel at 60 mg/m2 on day 1, cisplatin at 75 mg/m2 on day 2 and 5-FU at 200 mg/m2 with leucovorin at 20 mg/m2 daily from day 1 to day 5. At this dose, neutropenia was occurring in 4 of 6 patients treated. There were three partial responses, 1 patient with esophagogastric cancer and 2 with gastric cancer.


CONCLUSIONS
This regimen demonstrates efficacy in upper gastrointestinal malignancies. Strategies to improve the tolerance of these agents in combination should be pursued.
Mulcahy
Mary F
MF
Division of Hematology/Oncology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. mulcahy@northwestern.edu
Loehrer
Patrick J
PJ
Meropol
Neal J
NJ
Rademaker
Alfred W
AW
Benson Iii
Al B
AB
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy*; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
D043823:Taxoids; D000077143:Docetaxel; D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil