Phase II trial of cetuximab with or without paclitaxel in patients with advanced urothelial tract carcinoma

Abstract

Purpose: The benefit of salvage chemotherapy is modest in metastatic urothelial cancer. We conducted a randomized, noncomparative phase II study to measure the efficacy of cetuximab with or without paclitaxel in patients with previously treated urothelial cancer.

Patients and methods: Patients with metastatic urothelial cancer who received one line of chemotherapy in the perioperative or metastatic setting were randomly assigned to 4-week cycles of cetuximab 250 mg/m(2) with or without paclitaxel 80 mg/m(2) per week. We used early progression as an indicator of futility. Either arm would close if seven of the initial 15 patients in that arm progressed at the first disease evaluation at 8 weeks.

Results: We enrolled 39 evaluable patients. The single-agent cetuximab arm closed after nine of the first 11 patients progressed by 8 weeks. The combination arm completed the full accrual of 28 patients, of whom 22 patients (78.5%) had visceral disease. Twelve of 28 patients had progression-free survival greater than 16 weeks. The overall response rate was 25% (95% CI, 11% to 45%; three complete responses and four partial responses). The median progression-free survival was 16.4 weeks (95% CI, 12 to 25.1 weeks), and the median overall survival was 42 weeks (95% CI, 30.4 to 78 weeks). Treatment-related grade 3 and 4 adverse events that occurred in at least two patients were rash (six cases), fatigue (five cases), and low magnesium (three cases).

Conclusion: Although it had limited activity as a single agent, cetuximab appears to augment the antitumor activity of paclitaxel in previously treated urothelial cancers. The cetuximab and paclitaxel combination merits additional study to establish its role in the treatment of urothelial cancers.

Trial registration: ClinicalTrials.gov NCT00350025.

Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.

Kaplan-Meier curves for progression-free survival (PFS). NR, not reached.

Fig 2.

Kaplan-Meier curves for overall survival (OS).

Fig 3.

Waterfall plot of maximum changes in tumor volume for patients treated with paclitaxel and cetuximab. Three patients were not evaluable for response. M, patients who received chemotherapy for metastatic disease; P, patients who received perioperative chemotherapy.

Fig A1.

Statistical design and decision rules for each treatment cohort. es, early stopping.