Capecitabine in combination with mitomycin C in patients with gastrointestinal cancer: results of an extended multicentre phase-I trial

TY - JOUR

T1 - Capecitabine in combination with mitomycin C in patients with gastrointestinal cancer: results of an extended multicentre phase-I trial

AU - Hofheinz, R-D

AU - Hartmann, J T

AU - Willer, A

AU - Oechsle, K

AU - Hartung, G

AU - Gnad, U

AU - Saussele, S

AU - Kreil, S

AU - Bokemeyer, C

AU - Hehlmann, R

AU - Hochhaus, A

PY - 2004/8/31

Y1 - 2004/8/31

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Antineoplastic Agents

KW - Antineoplastic Combined Chemotherapy Protocols

KW - Deoxycytidine

KW - Dose-Response Relationship, Drug

KW - Female

KW - Fluorouracil

KW - Gastrointestinal Neoplasms

KW - Humans

KW - Male

KW - Maximum Tolerated Dose

KW - Middle Aged

KW - Mitomycin

KW - Treatment Outcome

U2 - 10.1038/sj.bjc.6602025

DO - 10.1038/sj.bjc.6602025

M3 - SCORING: Journal article

C2 - 15238990

VL - 91

SP - 834

EP - 838

JO - BRIT J CANCER

JF - BRIT J CANCER

SN - 0007-0920

IS - 5

ER -