title: Capecitabine in combination with mitomycin C in patients with gastrointestinal cancer: results of an extended multicentre phase-I trial.
abstract: The aim of this study was to determine the dose-limiting toxicity (DLT) and establish the recommended dose for mitomycin C added every 3 weeks to the standard combination dose of capecitabine. Cohorts of at least three patients with pretreated gastrointestinal carcinoma received capecitabine 1000 mg m(-2) orally twice daily on days 1-14 plus i.v. bolus mitomycin C on day 1 at doses of 4, 6, 8 or 10 mg m(-2) (corresponding to dose levels I-IV). Cycles were repeated every 3 weeks. Two treatment cycles were considered for the evaluation of DLTs. Of the 53 patients enrolled, the majority had colorectal (n=27) or gastric (n=14) cancers. Patients had received a median of two lines of prior chemotherapy (34% with >/=3 lines and 87% with prior 5-FU-based therapy). At the recommended dose level (IV, n=30), grade 3 adverse events during cycles 1 and 2 were: anaemia (10%); leukopenia (3%); thrombocytopenia (3%); stomatitis/mucositis (3%); hand-foot syndrome (3%). Two patients experienced DLTs (mucositis, n=1; neutropenic fever, n=1), but there were no grade 4 events. The median dose intensity for capecitabine and mitomycin C was 100% during cycles 1 and 2 and only four patients required postponement of therapy. Of the 43 patients evaluable for efficacy, seven achieved partial and minor remissions (16%; 95% CI, 5-28%), and 12 patients (28%) had stable disease. The favourable safety profile and promising activity of the capecitabine/mitomycin C combination, even in heavily pretreated patients, warrant further evaluation in patients with advanced colorectal and gastric cancers.
authors.affiliation: Onkologisches Zentrum, III. Medizinische Klinik, Fakultät für Klinische Medizin Mannheim der Universität Heidelberg, Theodor-Kutzer-Ufer, D-68167 Mannheim, Germany. ralf.hofheinz@med3.ma.uni-heidelberg.de
authors.forename: R-D
authors.initials: RD
authors.lastname: Hofheinz
authors.forename: J T
authors.initials: JT
authors.lastname: Hartmann
authors.forename: A
authors.initials: A
authors.lastname: Willer
authors.forename: K
authors.initials: K
authors.lastname: Oechsle
authors.forename: G
authors.initials: G
authors.lastname: Hartung
authors.forename: U
authors.initials: U
authors.lastname: Gnad
authors.forename: S
authors.initials: S
authors.lastname: Saussele
authors.forename: S
authors.initials: S
authors.lastname: Kreil
authors.forename: C
authors.initials: C
authors.lastname: Bokemeyer
authors.forename: R
authors.initials: R
authors.lastname: Hehlmann
authors.forename: A
authors.initials: A
authors.lastname: Hochhaus
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000069287:Capecitabine; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy*; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D016685:Mitomycin / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D003841:Deoxycytidine; D016685:Mitomycin; D000069287:Capecitabine; D005472:Fluorouracil