PHASE-II TRIAL OF DOCETAXEL (TAXOTERE(R)) IN METASTATIC COLORECTAL-CARCINOMA

Background. Docetaxel (Taxotere(R)) is prepared from a noncytotoxic pr ecursor extracted from the needles of the Taxus baccata. Preclinical i nvestigations have demonstrated that docetaxel is very active in colon adenocarcinoma murine models. Phase I studies revealed granulocytopen ia to be the dose-limiting toxicity. Initial clinical trials also demo nstrated docetaxers activity in ovarian, breast, and non-small cell lu ng cancer. Because of this encouraging preclinical and clinical activi ty, we initiated a phase II study of docetaxel in patients with metast atic colorectal carcinoma. Patients and methods: Docetaxel, 100 mg/M2, was administered as a 1-hour intravenous infusion every 21 days. Nine teen patients were entered on the trial. All patients had measurable d isease and had not received prior chemotherapy for metastatic disease. Results: No complete or partial responses were observed. Granulocytop enia was the dose-limiting toxic effect. Seventeen patients had grade 4 granulocytopenia; 8 of these patients received antibiotics for neutr openic fevers. Twelve patients experienced hypersensitivity reactions, and 15 patients experienced cutaneous toxic reactions. One patient de monstrated evidence of fluid retention. Conclusions: Administered at t he stated dose and schedule, docetaxel has little activity against met astatic colorectal carcinomas. The toxicity profile, consisting of gra nulocytopenia, hypersensitivity reactions, cutaneous reactions, and ed ema, has been previously described in patients receiving docetaxel.