Neoadjuvant chemo regimens compared for MIBC

September 17, 2018

“This is more evidence that [dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin] is highly effective for patients with bladder cancer,” says researcher Scott M. Gilbert, MD, MS.

Muscle-invasive bladder cancer patients treated with a dose-dense combination of methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) prior to cystectomy had better complete response and downstaging than patients treated with the neoadjuvant chemotherapy combination gemcitabine-cisplatin or gemcitabine-carboplatin, according to a recent study.

“This is more evidence that ddMVAC is highly effective for patients with bladder cancer,” said senior author Scott M. Gilbert, MD, MS, of the Genitourinary Oncology and Health Outcomes and Behavior Programs at Moffitt Cancer Center, Tampa, FL. The findings were published in JAMA Oncology (Aug. 30, 2018 [epub ahead of print]).

Neoadjuvant chemotherapy prior to cystectomy for muscle-invasive bladder cancer treatment is an evidence-based standard of care shown in studies to have about a 5% to 7% survival benefit at 10 years compared to surgery alone, according to Dr. Gilbert.

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Providers at most centers use gemcitabine with cisplatin as neoadjuvant therapy for these patients. In some cases, especially when a patient’s kidney function isn’t strong enough for cisplatin, physicians will use a neoadjuvant regimen of gemcitabine with carboplatin. The substitution from cisplatin to carboplatin has been a concern for Dr. Gilbert and others.

“I think there is concern that carboplatin is not as effective at controlling the cancer, so often we wonder whether it’s worth giving those patients chemotherapy before surgery,” Dr. Gilbert said. “Dose-dense MVAC is a new way to give the MVAC regimen that is being used at some academic centers. The standard MVAC regimen never really gained traction when it first became available, in large part due to side effects. The newer administration schedule, which gives all of the drugs over a shorter time period and includes medicine to support blood counts, helps get all those drugs in with fewer side effects.”

Dr. Gilbert and colleagues analyzed the medical records of 824 patients with disease stage T2 or greater who had cystectomy. Among those, 329 had no chemotherapy, 332 had neoadjuvant chemotherapy, and 163 had induction or adjuvant chemo. The authors used the surgery-only group as a benchmark. They categorized patients who received chemo prior to cystectomy and found: 204 had neoadjuvant chemotherapy with gemcitabine with cisplatin, 32 had gemcitabine with carboplatin, 46 had an average three cycles of ddMVAC, and 50 had other neoadjuvant chemo regimens.

Next:Downstaging, complete response ratesThey found downstaging rates were 52.2% for ddMVAC, 41.3% for gemcitabine-cisplatin, and 27% for gemcitabine with carboplatin. Complete response rates were 41.3% for ddMVAC, 24.5% for gemcitabine-cisplatin, and 9.4% for gemcitabine-carboplatin. Bladder cancer patients receiving ddMVAC had an 84% higher likelihood of downstaging compared to the gemcitabine-cisplatin group. And they were nearly 2.7-fold more likely to achieve a complete response. 

Giving bladder cancer patients gemcitabine-carboplatin before surgery was no better than doing surgical bladder removal alone.

The authors reported survival intervals were longer and risk of death lower for ddMVAC patients compared to those who received other treatments, but those results did not reach statistical significance and should be examined in larger comparative studies, according to the authors.

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“We also found that ddMVAC patients progress to surgery sooner than patients treated with the other chemotherapy regimens. So, there’s less of a delay,” Dr. Gilbert said. “For surgeons who perform cystectomy, this reaffirms that neoadjuvant chemotherapy is associated with downstaging and survival benefit, and that accelerated or dose-dense administration of MVAC is well tolerated and may be more effective than gemcitabine with cisplatin.”

Dr. Gilbert said that even though the study focused on types of neoadjuvant chemotherapy, it further supports use of neoadjuvant chemotherapy prior to cystectomy for muscle-invasive bladder cancer. Despite strong evidence supporting neoadjuvant chemotherapy for these patients, rates of adoption and routine use have been modest, according to the paper.

“This is not a definitive study because it was not a randomized controlled trial. We do need results from randomized controlled trials that are ongoing, which compare MVAC chemotherapy directly to gemcitabine with cisplatin,” Dr. Gilbert said.