Six cycles of neoadjuvant dose-dense gemcitabine and cisplatin (ddGC) is and effective therapeutic option with a favorable toxicity profile for patients with muscle invasive bladder cancer (MIBC), according to a study published in the Journal of Clinical Oncology.1
Dose-dense cisplatin-based neoadjuvant chemotherapy followed by radical cystectomy (RC) is the current standard of care for MIBC; previous studies assessing this intervention have demonstrated improved surgical outcomes and prolonged long-term survival. Various aspects of optimal treatment, such as optimal dose, drug combination, number of cycles, and duration of therapy, have yet to be clearly defined.
For this open-label, prospective phase 2 study (ClinicalTrials.gov Identifier: NCT01589094), researchers treated 49 patients with stage T2 to T4aN0M0 MIBC with neoadjuvant ddGC (gemcitabine 2500 mg/m2 on day 1 and cisplatin 35 mg/m2 on days 1 and 2) every 2 weeks for 6 cycles; the doses represented 1.875 and 1.5 times the standard doses of gemcitabine and cisplatin, respectively. Study patients underwent RC after completing chemotherapy.
Results showed that of the 46 evaluable patients, the pathologic response rate was 57% (95% CI, 42-70), leading to disease downstaging to less than pT2N0 and thereby meeting the primary endpoint of the study.
After a median follow-up of 25.6 months among surviving patients, median recurrence-free survival (RFS) and overall survival (OS) were not reached. Patients who responded to therapy were associated with improved OS and RFS; 2-year RFS rate was 96% and 52% among responders and non-responders, respectively, and 2-year OS rate was 96% and 84%, respectively (hazard ratio [HR], 0.15; 95% CI, 0.02-1.26; P = .043).
Thirty-nine percent of patients had to undergo dose modifications due to treatment toxicity, and 67% of patients completed all 6 cycles of treatment. No patient was unable to undergo RC due to treatment-related toxicity. The most commonly observed adverse effect was anemia.
Further analysis revealed that a predictor for positive treatment response was the presence of a presumed deleterious DNA damage response (DDR) gene alteration; 89% of patients with the gene responded to therapy, and had higher rates of 2-year RFS compared with patients who did not have this alternation.
- Iyer G, Balar AV, Milowsky MI, et al. Multicenter prospective phase II trial of neoadjuvant dose-dense gemcitabine plus cisplatin in patients with muscle-invasive bladder cancer [published online May 9, 2018]. J Clin Oncol. doi: 10.1200/JCO.2017.75.0158