A phase II trial of cisplatin, fixed dose-rate gemcitabine and gefitinib for advanced urothelial tract carcinoma: results of the Cancer and Leukaemia Group B 90102.

Abstract

OBJECTIVE:

To conduct a phase II trial to determine the efficacy of cisplatin, a fixed dose-rate infusion of gemcitabine and gefitinib (an orally active epidermal growth factor receptor tyrosine kinase inhibitor) in patients with advanced urothelial carcinoma.

PATIENTS AND METHODS:

Eligible patients had previously untreated measurable disease, an Eastern Cooperative Oncology Group performance status of 0-2 and creatinine clearance of >50 mL/min. The treatment regimen consisted of cisplatin 70 mg/m(2) on day 1, gemcitabine 1000 mg/m(2) on day 1 and 8, administered at a fixed dose rate of 10 mg/m(2)/min, given every 3 weeks concurrent with gefitinib 500 mg/day orally for a maximum of six cycles. Maintenance gefitinib 500 mg/day was continued for responding or stable disease.

RESULTS:

In all, 27 patients were accrued before the study was halted because the dose-limiting toxicity (DLT) exceeded pre-established stopping rules. The DLT events were two grade 5 (one infection, one cardiovascular accident) and three with grade 4 non-haematological toxicity. In 25 evaluable patients there were nine objective responses, for an overall response rate of 36% (95% confidence interval, CI, 18-57%). The median (95% CI) survival time was 11.1 (5.2-35.3) months.

CONCLUSION:

The combination of cisplatin, fixed dose-rate gemcitabine and gefitinib is active in advanced TCC, although the relative contribution of gefitinib cannot be determined. However, this regimen was associated with excessive toxicity.

• Authors: George K Philips, Susan Halabi, Ben L Sanford, Dean Bajorin, Eric J Small, Cancer and Leukaemia Group B
• Journal: BJU international (BJU Int) Vol. 101 Issue 1 Pg. 20-5 (Jan 2008) ISSN: 1464-410X [Electronic] England
• PMID: 17922873 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural)

Chemical References

• Quinazolines
• Deoxycytidine
• Cisplatin
• Gefitinib
• Gemcitabine

Topics

• Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Carcinoma, Transitional Cell (drug therapy)
• Cisplatin (administration & dosage)
• Deoxycytidine (administration & dosage, analogs & derivatives)
• Female
• Gefitinib
• Humans
• Male
• Middle Aged
• Quinazolines (administration & dosage)
• Treatment Outcome
• Urologic Neoplasms (drug therapy)
• Urothelium (pathology)
• Gemcitabine