Neoadjuvant Chemotherapy with Gemcitabine plus Cisplatin in Patients with Locally Advanced Bladder Cancer

Abstract

Background: Neoadjuvant chemotherapy with methotrexate-vinblastine-doxorubicin-cisplatin (MVAC) is the standard of care for muscle-invasive urothelial bladder cancer. Gemcitabine plus cisplatin (GC) shows similar efficacy with less toxicity in the metastatic setting and has therefore often been used interchangeably with MVAC. We report on the efficacy and safety of neoadjuvant GC in patients with locally advanced urothelial cancer. Materials and Methods: We prospectively evaluated 87 patients in 2 centers. Their median age was 68 years. Treatment consisted of 3× GC prior to radical cystectomy. The primary endpoint was pathologic response. The secondary endpoints were safety, progression-free survival (PFS), and overall survival (OS). Results: In all, 83 patients finished chemotherapy; 80 patients were evaluable for the primary endpoint. Pathologic complete response (pCR) was achieved in 22.5% and near pCR was seen in 33.7% of the patients. The 1-year PFS rate was 79.5% among those patients achieving ≤pT2 versus 100% among those patients achieving pCR or near pCR (p = 0.041). Five-year OS was 61.8% (95% CI 67.6 to NA). GC was well tolerated. Grade 3/4 toxicities occurred in 38% of the patients. There was no grade 3/4 renal toxicity, febrile neutropenia, or death. Conclusion: Neoadjuvant GC is a well-tolerated regimen. Although the pathologic response is lower than that reported with MVAC, our data support GC as a feasible option in the absence of a prospective randomized comparison, particularly for older patients, since its toxicity is lower than that of MVAC.

miR34a/GOLPH3 Axis abrogates Urothelial Bladder Cancer Chemoresistance via Reduced Cancer Stemness

“…The prognosis for patients with advanced or metastatic UBC remains poor. The vast majority of patients treated with cisplatin-based regimens develop progressive disease within 8 months of treatment, and the median survival was reported to be only 13-15 months 24 . CSCs may generate other CSCs and populations of cells forming the bulk of the tumor 9 , 25 .…”

Methionine Adenosyltransferase 1a (MAT1A) Enhances Cell Survival During Chemotherapy Treatment and is Associated with Drug Resistance in Bladder Cancer PDX Mice

“…Cancer becomes increasingly challenging to treat as it metastasizes to other tissues. Routine standard of care with first line chemotherapeutics typically result in tumor shrinkage, however, most cases relapse despite initial chemotherapeutic sensitivity and the recurring tumor is usually drug resistant [3]. For almost all cancer types, the emergence of drug resistance has long been a challenge in achieving a complete cure.…”

Treatment of elderly patients with advanced urological cancer

“…Based on these data, GC has become the preferred first-line therapy in cisplatin-eligible patients with metastatic UC [29]. In elderly patients who are "cisplatin-fit", GC similarly showed adequate efficacy with acceptable toxicity in the neoadjuvant setting [30][31][32][33]. For this age group, various doses of GC (gemcitabine doses ranging from 1,000-1,250 mg/m 2 and cisplatin doses ranging from 50-70 mg/m 2 ) were applied to UC cancer patients at Moffit Cancer Center over the years and then investigated in a retrospective analysis of 28 patients with a median age of 71 years.…”