Eribulin in advanced bladder cancer patients: a phase I/II clinical trial

This thesis summarized the results of a Phase I/II clinical trial of Eribulin in patients with locally advanced or metastatic bladder cancer and varying degrees of renal dysfunction. The objective of the safety lead‐in Phase I portion of this trial was to establish that Eribulin can be given safely to advanced bladder cancer patients with moderate or severe renal dysfunction at 1.4 mg/m²/week on days 1 and 8 of a 21‐day cycle. The objectives of the Phase II portion of this study included describing toxicity, response rate, progression free survival and overall survival in these patients. The associations of progression free survival and overall survival with covariates: prior treatment, gender and renal function were explored. A total of 154 patients were included in this study. The Phase I trial followed a modified 3+3 design. The dose was escalated from 0.7 mg/m²/week, 1.0 mg/m²/week, to 1.4 mg/m²/week. The Phase II trial followed a Simon Optimum two‐stage design. No serious Eribulin‐related adverse events have been reported. The overall response rate was 30%. Median progression free survival was 4.1 months (95% CI: 3.2, 4.5). Median overall survival was 9.6 months (95% CI: 7.6, 12.4). The probability of progression free survival at 6 and 12 months was 0.30 (95% CI: 0.22, 0.38) and 0.14 (95% CI: 0.07, 0.20), respectively. The probability of overall survival at 6,12 and 24 months was 0.67 (95% CI: 0.59, 0.76), 0.40 (95% CI: 0.31, 0.50) and 0.21 (95% CI: 0.12, 0.30), respectively. We did not identify any parameter that significantly correlated with better progression free survival or overall survival. Eribulin is a safe chemotherapy drug with promising single agent activity in bladder cancer patients with renal dysfunction.