4-Drug Regimen Preferred for Presurgical Bladder Cancer, But Drug Shortage Ensues

dd-MVAC did not improve overall survival compared to chemotherapy in certain patients with bladder cancer.

In some patients with bladder cancer, treatment with a combination of dose-dense methotrexate, vinblastine, Adriamycin (doxorubicin) and cisplatin (dd-MVAC; combination of chemotherapies) did not improve survival outcomes when compared with gemcitabine and cisplatin (GC; two types of chemotherapy) in a perioperative setting (time around surgery), according to a recent study, although dd-MVAC is still preferred bladder cancer treatment.

In specific, patients with muscle-invasive bladder cancer involved in the study did not have improved overall survival when receiving dd-MVAC versus GC perioperatively. Overall survival (OS) is the time from diagnosis or the start of treatment when patients with cancer are still alive, as defined by the National Cancer Institute.

Muscle-invasive bladder cancer, according to Johns Hopkins, is advanced bladder cancer when the tumor invades the bladder wall or spreads beyond the bladder.

READ MORE:Differentiating Muscle-Invasive, Non-Muscle-Invasive Bladder Cancer

However, researchers found data supported having six cycles of dd-MVAC compared with four cycles of GC in a neoadjuvant setting, meaning patients received dd-MVAC before the main treatment, which is typically surgery.

In the phase 3 study VESPER, 493 patients were randomly assigned into two groups and were evaluated based on OS and time to death from bladder cancer. In the dd-MVAC group, there were 248 patients, and there were 245 in the GC group. There were 408 patients who identified as male and 85 who identified as female.

At a median follow-up of 5.3 years, there were approximately 190 deaths reported. Researchers also determined that at five years, there was no difference OS when patients received dd-MVAC compared to GC. However, among patients who received chemotherapy before surgery, patients who received dd-MVAC showed more improvements compared with patients who received GC.

In terms of time-to-death caused by bladder cancer, the researchers found that time-to-death was increased in patients from the dd-MVAC group versus patients from the GC group.

“What [time-to-death] means is patients who received dd-MVAC have increased interval to death, [meaning they] live longer compared to the [GC] group,” Dr. Shifeng Mao, medical oncologist and chair of the urological oncology team at Allegheny Health Network, said during an interview with CURE®.

Mao noted that in real-world settings, the dd-MVAC treatment combination was not being used as medical centers encountered a “major problem” with the drug shortage near the end of 2023. He explained that with the shortage of vinblastine in dd-MVAC, there was no way doctors could use the treatment combination.

“[Doctors] can’t [use] MVAC because one of the four drugs is missing,” Mao said. “So by default, I’ve had to use gemcitabine and cisplatin in recent months, since around October or November. Until vinblastine becomes available, I am forced to use gemcitabine and cisplatin, even though personally, I prefer dose-dense MVAC.”

For now, the use of dd-MVAC is on hold until the shortage of vinblastine ends, Mao said.

“The most recent rumor is [vinblastine may be available] maybe sometime in February. So as of now, we don't have it; that's the situation,” he said. “Certainly, the drug shortage has an impact on daily practice and affects oncology care to a great deal.”

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