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

Overview

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/m(2) and gemcitabine 2, 000 mg/m(2), to determine the MTD of the regimen. The dose and schedule of ITP were constant: ifosfamide 1,500 mg/m(2) (days 1 to 3); paclitaxel 200 mg/m(2) (day 1); and cisplatin 70 mg/m(2) (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.

publication date

  • February 1, 2000

Research

keywords

  • Antibiotics, Antineoplastic
  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents
  • Antineoplastic Agents, Alkylating
  • Antineoplastic Agents, Phytogenic
  • Antineoplastic Combined Chemotherapy Protocols
  • Carcinoma, Transitional Cell
  • Cisplatin
  • Deoxycytidine
  • Doxorubicin
  • Ifosfamide
  • Paclitaxel
  • Urologic Neoplasms

Identity

Scopus Document Identifier

  • 0033956934

Digital Object Identifier (DOI)

  • 10.1200/JCO.2000.18.4.840

PubMed ID

  • 10673526

Additional Document Info

volume

  • 18

issue

  • 4