title: Protracted infusional 5-fluorouracil plus high-dose folinic acid combined with bolus mitomycin C in patients with gastrointestinal cancer: a phase I/II dose escalation study.
abstract: The aim of this study was to define the maximum tolerated dose (MTD) of bolus mitomycin C (MMC) in combination with 24 h-continuous infusion of 5-flourouracil (FU) plus folinic acid, and to assess the toxicity and activity in patients with previously treated colorectal and gastric cancer. Escalating doses of MMC starting from 6 mg m(-2) in 2 mg m(-2)-steps to a maximum of 10 mg m(-2) were applied on days 1 and 22, given to fixed doses of 5-FU (2.600 mg m(-2)) as 24 h infusion and folinic acid 500 mg m(-2) prior to 5-FU weekly for 6 weeks. At least three patients were treated at each dose level. A total of 16 patients have been included in the phase I study. At the highest dose level (MMC 10 mg m(-2)), grade III thrombocytopenia, dyspnoea, mucositis and diarrhoea were observed in one patient each (17 %). In the phase II study 45 patients, 33 with colorectal cancer and 12 with gastric cancer, 23 patients after failure of first- and 22 patients after at least second-line or subsequent chemotherapy have been treated. Seven partial responses (PR) were registered (16%), one (3%; CI(95%), 0-16) in colorectal and six (50%; CI(95%), 21-79%) in gastric cancer patients. In all, 17 (38%) achieved disease stabilisation, 15 colorectal (45%, CI(95%), 28-64%) and two gastric cancer patients (17%; CI(95%), 2-48%). The median progression-free survival was 3.1 months (range, 0.9-9.1) in colorectal and 4.6 months (range, 0.7-12.4) in gastric cancer. The median overall survival time was 6.6 months (range, 1.9-15.6) in colorectal and 7.1 months (range, 1.7-20.8) in patients with gastric cancer. This regimen was considered to be safe and well tolerated for pretreated patients with gastrointestinal adenocarcinoma. In gastric cancer,MMC plus infusional 5-FU/folinic acid may be a potential second-line regimen with promising antitumour activity.
authors.affiliation: Abt. Hämatologie/Onkologie/Immunologie/Rheumatologie, Medizinische Klinik II, Eberhard-Karls-Universität, Tuebingen, Germany. joerg.hartmann@med.uni-tuebingen.de
authors.forename: J T
authors.initials: JT
authors.lastname: Hartmann
authors.forename: K
authors.initials: K
authors.lastname: Oechsle
authors.forename: D
authors.initials: D
authors.lastname: Quietzsch
authors.forename: A
authors.initials: A
authors.lastname: Wein
authors.forename: R D
authors.initials: RD
authors.lastname: Hofheinz
authors.forename: F
authors.initials: F
authors.lastname: Honecker
authors.forename: O
authors.initials: O
authors.lastname: Nehls
authors.forename: C-H
authors.initials: CH
authors.lastname: Köhne
authors.forename: G
authors.initials: G
authors.lastname: Käfer
authors.forename: L
authors.initials: L
authors.lastname: Kanz
authors.forename: C
authors.initials: C
authors.lastname: Bokemeyer
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy*; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D016685:Mitomycin; D016896:Treatment Outcome
chemical_list: D016685:Mitomycin; D002955:Leucovorin; D005472:Fluorouracil