Accelerated Methotrexate, Vinblastine, Doxorubicin, and Cisplatin for Muscle-Invasive Bladder Cancer: Real-World Feasibility and Safety in a Resource-Constrained Setting

PURPOSE: Muscle-invasive bladder carcinoma (MIBC) poses major treatment challenges in low- and middle-income countries because of logistical and socioeconomic barriers limiting neoadjuvant chemotherapy (NAC) delivery. While dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) improves pathologic response and survival over gemcitabine-cisplatin, its multiday schedule reduces practicality. Accelerated MVAC (AMVAC), a single-day outpatient regimen, may offer a feasible alternative. This study evaluated the feasibility and safety of AMVAC in Indian patients with MIBC. METHODS: We conducted a single-arm feasibility study at the All India Institute of Medical Sciences, Rishikesh, India, between December 2021 and November 2024. Adults with stage II-III MIBC and cisplatin eligibility received 3-4 cycles of single-day AMVAC with pegfilgrastim support before radical cystectomy. Feasibility was defined as completion of ≥3 or 4 cycles within protocol-specified timeframes. Toxicities were graded using CTCAE v5.0, and outcomes were analyzed descriptively. RESULTS: Sixty patients were enrolled (mean age 55.2 ± 11.2 years; 90% male); 55 received neoadjuvant, and five adjuvant therapy. The mean number of chemotherapy cycles delivered was 3.87 ± 0.85. Feasibility outcomes were favorable, with 91.6% completing three and 76.6% completing four cycles within protocol timelines. Dose reductions for grade ≥3 toxicities were required in 13 patients (21.7%), whereas four patients discontinued treatment because of reduced creatinine clearance. Grade 3 adverse events occurred in 38.3%, most commonly anemia (16.7%), fatigue, and mucositis (13.3% each). Among neoadjuvant recipients undergoing cystectomy (n = 40), pathologic complete response (PCR) was achieved in 32.5% and pathologic downstaging was achieved in 55%. CONCLUSION: Single-day AMVAC is a feasible and tolerable NAC regimen in a resource-constrained setting, with encouraging PCR and manageable toxicity.