September 18, 2018
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Dose-dense chemotherapy improves bladder cancer outcomes following cystectomy

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Photo of Scott Gilbert 2018
Scott Gilbert

Neoadjuvant chemotherapy comprised of a dose-dense combination of methotrexate, vinblastine, doxorubicin and cisplatin improved response rates among patients with bladder cancer undergoing cystectomy compared with the standard combination of gemcitabine and cisplatin, according to study findings.

“The best survival results for patients with muscle invasive bladder cancer who are treated with neoadjuvant chemotherapy and surgery are seen with [methotrexate, vinblastine, doxorubicin and cisplatin],” Scott Gilbert, MD, MS, associate member in the Genitourinary Oncology and Health Outcomes & Behavior Programs at Moffitt Cancer Center, told HemOnc Today. “If patients are eligible for this chemotherapy regimen, it is associated with the best chance that the cancer will be downstaged, which also translates to higher survival.”

Research has suggested a combination of methotrexate, vinblastine, doxorubicin and cisplatin (ddMVAC) administered on a dose-dense accelerated schedule exhibited noninferior safety and efficacy to the standard neoadjuvant combination of gemcitabine and cisplatin.

However, few studies have compared neoadjuvant regiments in terms of cancer control and survival outcomes.

Researchers evaluated medical records of 1,113 patients (median age, 67 years; 77.4% men; 94.4% white) who underwent cystectomy for bladder cancer from 2007 to 2017 at Moffitt Cancer Center. Among them, 824 had been diagnosed with invasive or advanced cancers, of whom 332 received chemotherapy prior to surgery.

A majority of patients (n = 204; 61.4%) received gemcitabine and cisplatin, the standard neoadjuvant chemotherapy for bladder cancer, whereas 46 patients (14%) received ddMVAC on a dose-dense accelerated schedule. Thirty-two patients (10%) received gemcitabine and carboplatin, and the remainder 50 patients (15.1%) received other regimens.

Downstaging occurred among 52.2% of patients who received ddMVAC, 41.3% of those who received gemcitabine-cisplatin and 27% of those who received gemcitabine-carboplatin.

A greater proportion of patients who received ddMVAC (24.5%) than gemcitabine-cisplatin (24.5%) and gemcitabine-carboplatin (9.4%) achieved a complete response (2-sided P<.001).

Adjusted analysis comparing ddMVAC with gemcitabine-cisplatin showed an increased likelihood of downstaging (OR = 1.84; 95% CI, 1.1-3.09) and complete response (OR = 2.67; 95% CI, 1.5-4.77) with ddMVAC. Propensity score matching indicated similar results (OR = 1.52; 95% CI, 0.99-2.35).

Patients who received ddMVAC had better OS than patients treated with other chemotherapy regimens; however, the survival benefit observed by researchers did not reach statistical significance in adjusted or propensity-matched analyses (HR = 0.44; 95% CI, 0.14-1.38).

Researchers also found the gemcitabine-carboplatin combination appeared “essentially ineffective,” with a higher risk for death observed in this group (HR = 2; 95% CI, 1.19-3.38).

Gilbert cited the cross-sectional retrospective design as the study’s biggest limitation.

“Because this was not a randomized controlled trial, there may be biases that influenced who received ddMVAC and who did not,” he said. “We adjusted for potential biases as much as possible, but these results shouldn’t necessarily be considered definitive.”

More randomized studies comparing neoadjuvant chemotherapy regimens are needed. Two randomized trials — Southwestern Oncology Group 1314 and VESPER — are underway, according to Gilbert, but results are not expected until 2021 or 2022.

“We hope that our results encourage medical oncologists and urologists who treat muscle-invasive bladder cancer to consider ddMVAC when possible, and that neoadjuvant gemcitabine and carboplatin not be routinely used due to its limited effectiveness,” Gilbert said. – by Melinda Stevens

For more information:

Scott Gilbert, MD, can be reached at Moffitt Cancer Center, Vincent A. Stabile Research Building, 12902 USF Magnolia Drive, Tampa, FL 33612.

Disclosures: The authors report no relevant financial disclosures.