Efficacy of Split Schedule Versus Conventional Schedule Neoadjuvant Cisplatin-Based Chemotherapy for Muscle-Invasive Bladder Cancer

Abstract

Neoadjuvant cisplatin‐based chemotherapy (NAC; 70 mg/m2) is standard of care for muscle‐invasive bladder carcinoma (MIBC). Many patients (pts) cannot receive cisplatin because of renal impairment, and administration of cisplatin 35 mg/m2 on day 1 + 8 or 1 + 2 (i.e., split schedule) is a commonly used alternative. In this retrospective analysis, we compared complete (pT0) and partial (<pT2) pathologic response rates between split schedule (SS) and conventional schedule (CS) pts, after 1:1 matching on chemotherapy regimen, number of cycles, tumor histology, and clinical stage. Eighty matched pts were identified. pT0 rates were 17.5% (95% confidence interval [CI], 7%–33%) and 32.5% (95% CI, 19%–49%) in SS and CS cisplatin pts, respectively (p = .21), corresponding to an odds ratio for pT0 of 0.45 (95% CI, 0.16–1.31) with SS cisplatin. Split schedule cisplatin was associated with numerically but not statistically significant lower pathologic response rates relative to full dose.

Prediction of pathological response following neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer: the PRE-PREVENCYS trial

“…The decision to give dose-dense Methotrexate, Vinblastine, Adriamycin and Cisplatin (ddMVAC) every two weeks or Gemcitabine and Cisplatin (Gem/Cis) every three weeks as cisplatin-based NAC is determined by the medical oncologist according to local hospital protocols. Patients with a Creatinine Clearance (CrCl) between 40 and 60 ml/min are eligible for split-dose cisplatin and gemcitabine [20].…”

“…A further exclusion criterion is the presence of CIS in the prostatic urethra at diagnostic TUR, since the prostatic urethra is a difficult site for re-staging TUR biopsies, especially within a close surveillance protocol. Split-dose cisplatinbased NAC regimens for patients with impaired renal function are allowed within the PRE-PREVENCYS trial as these regimens have been shown non-inferior to conventional regimens in terms of pathological downstaging [20]. Therefore, patients with a CrCl between 40 and 60 ml/min are thus candidates for this split-dose regimen and will be included in this study.…”

Current Management of Localized Muscle-Invasive Bladder Cancer: A Consensus Guideline from the Genitourinary Medical Oncologists of Canada

“…Timed urine collections, although preferable, are infrequently utilized due to inconvenience and cost. In patients with impaired renal function (renal clearance ≥50 mL/min), split dose GC (cisplatin 35 mg/m 2 on day 1 and day 8) [81,91,[162][163][164][165] and dose reduction (25-50%) of standard GC (cisplatin 70 mg/m 2 every 3 weeks) are options, although data supporting these approaches remains limited [166][167][168]. For patients with baseline renal function <50 ml/min, generally the use of cisplatin-based NAC is not supported by adequate safety data.…”

The Quest for an Ideal Neoadjuvant Systemic Therapy in Cisplatin-Ineligible Patients with Muscle-Invasive Localized Urothelial Carcinoma

“…In the current issue of The Oncologist , Osterman et al report results of a retrospective multi‐institutional 1:1 matched cohort study of 80 patients with MIBC who received either split‐dose or conventional‐dose CBNCC. In comparison with conventional dose, patients receiving split dose were older (71 vs. 65.5 years, p = .007) and had lower median glomerular filtration rate (63.5 vs. 74.7 mL/min, p = .003).…”

“…Moreover, The Cancer Genome Atlas has reported potential therapeutic targets in 69% of the analyzed tumors, which provides the setting for evaluation of new therapeutic approaches [17]. At present, more than 50 neoadjuvant trials are ongoing in MIBC [18]. These trials include PD-1/PD-L1 therapies either as a single agent or in combination with CTLA-4 antibodies, other checkpoint inhibitors, chemotherapy, PARP inhibitors, or other agents.…”