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.
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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.
Reference
- 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
