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 À2 b.i.d. on days 1 -14, docetaxel 40 mg m À2 i.v. day 1, mitomycin C 4 or 6 mg m À2 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 ¼ 40). 14 pts had received X3 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 À2 ) and mitomycin C (4 mg m À2 ). The established regimen was well tolerated and the preliminary efficacy data in this heavily pre-treated patients population appears to be promising.

Efficacy and safety of capecitabine in combination with docetaxel and mitomycin C in patients with pre-treated pancreatic, gallbladder, and bile duct carcinoma

“…In a previous phase-I trial, we have established a regimen using capecitabine in combination with MMC as well as docetaxel (Ernst et al 2007), which demonstrated activity in bile duct and pancreatic carcinoma. Moreover, the results of several clinical trials in various types of cancer indicate that capecitabine in combination with either of these TP inductors bears promising activity.…”

“…Patients had previously received at least one line of palliative chemotherapy, usually gemcitabine. The analysis reports the long-term results of all consecutive patients with gallbladder, bile duct or pancreatic carcinoma treated either on a compassionate use basis in our department (n = 10) or within the phase-I trial (n = 18; Ernst et al 2007), which was reviewed and approved by the local institutional review board and which was performed to the Declaration of Helsinki. All patients within the phase-I trial provided written informed consent prior to entry into the study.…”

“…The combination of docetaxel, MMC and capecitabine (DocMitoCape) was tested in a phase-I study including patients with pre-treated gastrointestinal tumors (Ernst et al 2007). This combination was well tolerated and showed encouraging signs of activity especially in patients with pancreatic and bile duct cancer.…”

Capecitabine-induced stomatitis: a likely pathogenetic mechanism of oral lichenoid mucositis

“…Although the frequency of grade 3/4 toxicities occurring with capecitabine alone or in combination with lapatinib has been reported to be very low (0-1%), the oral adverse event described as stomatitis and/or mucositis [6,7] occurs at a frequency of 11-15% (all grades) [2,3].…”