Phase I evaluation of sequential doxorubicin + gemcitabine then ifosfamide + paclitaxel + cisplatin for patients with unresectable or metastatic transitional-cell carcinoma of the urothelial tract

PURPOSE: This phase I trial sought to evaluate the toxicity of and determine the maximum-tolerated dose (MTD) for the two-drug regimen doxorubicin and gemcitabine (AG) followed by the three-drug regimen of ifosfamide, paclitaxel, and cisplatin (ITP) in patients with unresectable or metastatic transitional-cell carcinoma. PATIENTS AND METHODS: Patients received AG every other week for six cycles followed by ITP every 3 weeks for four cycles. Five AG dose levels were investigated, up to doxorubicin 50 mg/m2 and gemcitabine 2,000 mg/m2, to determine the MTD of the regimen. The dose and schedule of ITP were constant: ifosfamide 1,500 mg/m2 (days 1 to 3); paclitaxel 200 mg/m2 (day 1); and cisplatin 70 mg/m2 (day 1). Granulocyte colony-stimulating factor was given between all cycles of therapy. RESULTS: Fifteen patients enrolled onto this phase I trial. AG was well tolerated at all dose levels, with no grade 3 or 4 myelosuppression. Toxicity experienced with ITP included grade 3 and 4 granulocytopenia in four p...