| Abstract: |
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 patients and grade 3 nausea/vomiting in three patients. No grade 3 and 4 neurotoxicity was observed. Eight of 14 assessable patients experienced a major response to AG, including five of six patients treated at the two highest AG dose levels. After completion of AG-ITP, nine of 14 assessable patients had a major response (three complete responses and six partial responses). Conclusion: AG is a well-tolerated and active regimen. Sequential chemotherapy with AG-ITP is also well tolerated, and phase II investigation at the highest dose level is ongoing. (C) 2000 American Society of Clinical Oncology. |
| Keywords: |
adult; cancer chemotherapy; clinical article; treatment outcome; aged; middle aged; clinical trial; cisplatin; doxorubicin; cancer combination chemotherapy; drug efficacy; antineoplastic agents; gemcitabine; paclitaxel; antineoplastic agent; bone marrow cells; antimetabolites, antineoplastic; nausea; vomiting; antineoplastic combined chemotherapy protocols; antineoplastic agents, phytogenic; ifosfamide; urologic neoplasms; antineoplastic agents, alkylating; urinary tract cancer; remission induction; carcinoma, transitional cell; antibiotics, antineoplastic; bladder carcinoma; deoxycytidine; transitional cell carcinoma; granulocyte colony stimulating factor; granulocyte colony-stimulating factor; drug induced disease; granulocytopenia; agranulocytosis; humans; human; male; female; priority journal; article
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