medwireNews: Neoadjuvant chemotherapy with dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) achieves better outcomes than gemcitabine plus cisplatin or carboplatin in patients with muscle-invasive bladder cancer, research shows.
Among the 824 patients with stage T2 or greater disease included in the study, those who received ddMVAC (n=46) prior to radical cystectomy were a significant 1.84 times more likely to achieve pathologic downstaging and 2.67 times more likely to have a complete pathologic response (pT0N0) than those treated with gemcitabine–cisplatin (n=204) during a median 18.6 months of follow-up.
Specifically, downstaging rates were 52.2% for ddMVAC and 41.3% for gemcitabine–cisplatin, while complete pathologic response rates were 41.3% and 24.5%, respectively.
By comparison, downstaging and complete response rates were 27.0% and 9.4%, respectively, among patients who received gemcitabine–carboplatin (n=32), and 25.7% and 10.7%, respectively among those who received no adjuvant chemotherapy (n=777).
Estimated 2-year overall survival rates were 73.3%, 62.0%, and 34.8% with ddMVAC, gemcitabine–cisplatin, and gemcitabine–carboplatin, respectively.
Adjusted analyses indicated that the estimated risk for death was 58% lower with ddMVAC than with gemcitabine–cisplatin, but the difference was not statistically significant, possibly due to the small sample size, the researchers suggest.
In spite of this, “the magnitude of the survival differences that we observed were substantial and suggest the clinical importance of the findings,” Scott Gilbert (H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA) and co-authors write in JAMA Oncology.
They add: “Another important finding of the present study was that neoadjuvant gemcitabine-carboplatin appears essentially ineffective,” noting that the adjusted risk for death was a significant twofold higher among patients receiving this treatment than among those who received gemcitabine–cisplatin.
“These results raise questions regarding the role of neoadjuvant gemcitabine-carboplatin,” Gilbert et al remark.
The team also found that patients who received ddMVAC underwent surgery 24 and 39 days earlier than those who received gemcitabine–cisplatin and gemcitabine–carboplatin, respectively.
Gilbert and colleagues conclude: “Although gemcitabine with cisplatin is the most frequently prescribed neoadjuvant chemotherapy regimen for patients with muscle-invasive bladder cancer, for eligible patients, treatment with [ddMVAC] may lead to better outcomes.”
They add: “These data highlight and suggest the need to further investigate ddMVAC vs standard [neoadjuvant chemotherapy] in a prospective, randomized fashion.
By Laura Cowen