Accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) as neoadjuvant chemotherapy for patients with muscle‐invasive transitional cell carcinoma of the bladder

Abstract

BACKGROUND:Meta-analysis data demonstrate a 5% absolute survival benefit for neoadjuvant chemotherapy (NAC) using cisplatinbased combination regimens in the radical treatment of muscle-invasive bladder cancer (MIBC). However, there are no randomized, controlled trial data on the optimum regimen. Accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) is a doseintense regimen that has the potential to minimize delays to definitive, potentially curative therapy. A retrospective analysis is presented of the efficacy and toxicity of AMVAC as NAC in patients with MIBC and its impact on the patient pathway. METHODS: Eighty consecutive patients with MIBC were treated with AMVAC as NAC by 2 UK multidisciplinary uro-oncology teams. Three or 4 cycles of AMVAC (methotrexate 30 mg/m 2 , vinblastine 3 mg/m 2 , doxorubicin 30 mg/m 2 , and cisplatin 70 mg/m 2 ) were given at 2-week intervals, with granulocyte colony-stimulating factor support, prior to either radical surgery or radical radiotherapy. RESULTS: All planned cycles of chemotherapy were completed, without dose reduction or delay in 84% of patients. All 80 patients subsequently received their planned definitive therapy. Grade 3/4 toxicities were seen in 26% of the 42% of patients for whom toxicity data are available, including 12% grade 3/4 neutropenia. Pathological complete response to AMVAC was seen in 43% of 60 surgical patients. Objective radiological local response was seen in 83% of 57 evaluable patients. Two-year disease-free and overall survival were 65% and 77%, respectively. CONCLUSIONS: AMVAC is safe and appears to be a well-tolerated and effective NAC regimen for MIBC. It minimizes delays to definitive treatment and produces excellent pathological and radiological response rates. It is an appropriate comparator for future randomized trials. Cancer 2012;118:3920-7.

Neoadjuvant induction dose-dense MVAC for muscle invasive bladder cancer: efficacy and safety compared with classic MVAC and gemcitabine/cisplatin

“…This is considerably higher than the toxicity incidence of 10-12 % reported in the two prospective neoadjuvant dd-MVAC studies [12,13]. However, our results are in line with dd-MVAC tolerability observed by Blick et al [14]. They reported high-grade toxicities in 26 % of 34 retrospectively analyzed patients who had received 3-4 cycles of dd-MVAC followed by surgery or radiotherapy.…”

“…Currently, available data on efficacy and tolerability of dd-MVAC are largely based on reports in the palliative setting [8,[12][13][14]. The present study was conducted in order to investigate the efficacy and safety of neoadjuvant dd-MVAC, resulting in evident pathological downstaging in patients with locally advanced and/or node-positive urothelial MIBC.…”

Systemic, perioperative management of muscle-invasive bladder cancer and future horizons

“…Importantly, the dose-dense approach can decrease the time between the start of MVAC chemotherapy and the point of surgery, with a median time of 9.7 weeks reported in the study by Plimack et al 78 (compared with 16–19 weeks for the standard regimens 14,72 ). The results of these two prospective trials 77,78 (TABLE 4), as well as those from two retrospective studies 79,80 , are promising; however, the authors of an editorial 81 , which accompanied the trial publications, identified issues regarding patient selection that might limit the generalizability of the results. For example, both trials included patients with N1 disease, therapy for whom, as previously discussed, cannot truly be considered ‘neoadjuvant’.…”

Comparative effectiveness of gemcitabine plus cisplatin versus methotrexate, vinblastine, doxorubicin, plus cisplatin as neoadjuvant therapy for muscle‐invasive bladder cancer

“…30,31 A retrospective analysis of 80 consecutive patients who received dose-dense MVAC also generated consistent results. 32 Indeed, several of the centers involved in those studies contributed patient data to RISC, accounting for the predominance of dose-dense MVAC in our MVAC cohort. Although the majority of patients (77%) received dose-dense MVAC in our analysis, no significant difference in the pCR rate was observed between neoadjuvant GC and MVAC.…”