title: Capecitabine in combination with docetaxel and mitomycin C in patients with pre-treated tumours: results of an extended phase-I trial.
abstract: Preclinical data suggest that the anti-tumour activity of capecitabine is enhanced by taxanes and mitomycin C through up-regulation of thymidine phosphorylase (TP). Here, we studied safety and efficacy of the combination of capecitabine with docetaxel and mitomycin C. Two dose levels (DL) were investigated: capecitabine 1000 mg m(-2) b.i.d. on days 1-14, docetaxel 40 mg m(-2) i.v. day 1, mitomycin C 4 or 6 mg m(-2) i.v. day 1 (DL I or II). Cycles were repeated every 3 weeks. The primary aim was to determine the dose-limiting toxicities (DLT) during the first two treatment cycles and the maximum tolerated dose (MTD). A total of 46 patients (pts) refractory to standard therapies were enrolled, of whom the majority had gastrointestinal tumours (n=40). 14 pts had received >/=3 lines of prior chemotherapy. At DL I, one out of six pts experienced DLT. At DL II, two out of six pts had DLT (mucositis grade 3). Thus, DL I was determined as MTD. Among a total of 37 pts treated on DL I the following toxicities were observed during cycles 1 and 2 (number of patients with grade 1/2/3/4 toxicity; NCI-CTC v. 3.0): anaemia 10/8/3/0, leucocytopenia 4/11/1/2, thrombocytopenia 0/1/2/0, diarrhoea 8/1/2/0, stomatitis/mucositis 3/3/1/0, nausea/vomiting 10/2/0/0, and hand-foot skin reaction 5/1/1/0. Of 30 pts who received at least two treatment cycles nine achieved complete or partial remissions, six pts achieved minor remissions, and seven pts had stable disease (tumour control rate 73%). Of note, four out of 10 patients with pancreatic cancer had partial remissions. In conclusion, capecitabine can safely be combined with docetaxel (40 mg m(-2)) and mitomycin C (4 mg m(-2)). The established regimen was well tolerated and the preliminary efficacy data in this heavily pre-treated patients population appears to be promising.
authors.affiliation: Onkologisches Zentrum, III. Medizinische Klinik, Medizinische Fakultät Mannheim der Universität Heidelberg, Theodor-Kutzer-Ufer 1-3, Mannheim 68167, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Ernst
authors.forename: K
authors.initials: K
authors.lastname: Merx
authors.forename: U
authors.initials: U
authors.lastname: Gnad-Vogt
authors.forename: N
authors.initials: N
authors.lastname: Lukan
authors.forename: M
authors.initials: M
authors.lastname: Kripp
authors.forename: B
authors.initials: B
authors.lastname: Schultheis
authors.forename: A
authors.initials: A
authors.lastname: Hochhaus
authors.forename: R-D
authors.initials: RD
authors.lastname: Hofheinz
mesh_terms: D000328:Adult; D000368:Aged; D000740:Anemia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D003967:Diarrhea / Q000139:chemically induced; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D007262:Infusions, Intravenous; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage / Q000009:adverse effects; D009325:Nausea / Q000139:chemically induced; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D012871:Skin Diseases / Q000139:chemically induced; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced
chemical_list: D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D016685:Mitomycin; D000069287:Capecitabine; D005472:Fluorouracil