A phase II trial and pharmacokinetic analysis of 96-hour infusional paclitaxel in patients with metastatic colorectal cancer

A phase II study was conducted to evaluate the activity and toxicity of 96- hour infusional paclitaxel in patients with previously untreated metastatic colorectal cancer. Twelve patients were enrolled in this study. The first patient received a total dose of 140 mg/m(2) over 96 hours resulting in gra de 4 neutropenia, neutropenic fever, and grade 3 stomatitis. Subsequent pat ients received a total dose of 120 mg/m(2) over 96 hours. Grade 3 to 4 neut ropenia occurred in four of these patients. No significant thrombocytopenia was observed. Grade 3 to 4 nonhematologic toxicities in the group treated at 120 mg/m(2) over 96 hours included nausea/vomiting in one patient, stoma titis in one patient, and diarrhea in two patients. One patient experienced a possible pulmonary hypersensitivity reaction. None of the 12 patients ac hieved an objective response. Two patients had stable disease and ten had p rogressive disease. Pharmacokinetic parameters including maximum plasma con centration and area under the concentration time curve were significantly h igher in patients with grade 3 to 4 neutropenia than patients who experienc ed less toxicity. The authors conclude that further study of 96-hour infusi onal paclitaxel in patients with metastatic colorectal carcinoma is not war ranted.