Dose-Dense Chemo for Muscle-Invasive Bladder Cancer May Be Feasible

The treatment of preoperative dose-dense gemcitabine and cisplatin chemotherapies was well-tolerated and effective in patients with locally advanced muscle-invasive bladder cancer; however, more research is needed, an expert told CURE®.

“The dose-dense part means to shrink the duration of the [chemotherapy] cycle, so we give gemcitabine and cisplatin in a two-week course instead of a three-week course,” explained Dr. Umang Swami, assistant professor in the division of oncology, Department of Internal Medicine at Huntsman Cancer Institute at the University of Utah, during an interview with CURE®.

In a retrospective Japanese study published in the International Journal of Urology, 45 patients with locally advanced muscle-invasive bladder cancer were included. Patients in the study were treated with dose-dense gemcitabine and cisplatin between December 2017 and December 2023. Of the 45 patients, 41 underwent radical cystectomy (surgery to remove the entire bladder) and were evaluated for complete responses to treatment (complete disappearance of cancer) and objective response rates (percentage of patients whose cancer shrunk or disappeared).

Among the 41 patients who received a radical cystectomy, 38 patients completed all planned cycles of treatment, according to the researchers. Complete responses (meaning that all signs of cancer disappeared) were achieved in 12 patients and objective responses (cancer shrunk) in 17.

“This dose-dense chemotherapy has shown to shorten the time for surgery without compromising treatment efficacy when compared to standard treatments in general,” Swami said.

Traditional Treatments and Side Effects

The standard of care for patients with locally advanced muscle-invasive bladder cancer was a chemotherapy regimen of gemcitabine and cisplatin — but not a dose-dense version, Swami said.

Respective patients could also receive dose-dense methotrexate, vinblastine, Adriamycin (doxorubicin) and cisplatin (a regimen referred to as MVAC), Swami noted. The phase 3 VESPER trial compared dose-dense MVAC to a gemcitabine and cisplatin combination in the neoadjuvant (presurgical) setting.

In terms of side effects, the researchers from the Japanese study reported that grade 3 (severe) or worse were observed in eight patients, the study researchers established, of which four patients experienced blood toxicities.

“The main side effects were anemia and thrombocytopenia, meaning there were low [amounts of] red blood cells and platelets,” Swami said. “There were other side effects, including infection, hyperkalemia (abnormally high levels of potassium), dehydration and upper gastrointestinal hemorrhage when we use [dose-dense] MVAC. [Other] main side effects are mostly hematological (blood related), meaning we see a lot of anemia and asthenia, meaning fatigue, and nausea and vomiting. So these are the main side effects, which we notice with the dose-dense regimens.”

The Study’s Importance for Patients With Muscle-Invasive Bladder Cancer

For patients with muscle-invasive bladder cancer, Swami noted that it’s important for patients to know that the treatment of dose-dense gemcitabine and cisplatin is still feasible, although a phase 3 study needs to confirm this.

“We still need patients to discuss with their oncologist what is the best treatment regimen for them based on their cancer type, their comorbidities, disease characteristics, clinical features, etc.,” he said. “One thing which I would like to point out is that this study, again, was a retrospective single-center study, [meaning] it's hard to compare and say that [dose-dense MVAC] is better or worse than or equivalent to gemcitabine and cisplatin, or whether it's better, same or worse than dose-dense MVAC.”

LEARN MORE: 4 Questions to Ask After a Bladder Cancer Diagnosis

Before patients undergo dose-dense gemcitabine and cisplatin, Swami emphasized the need for patients to keep themselves hydrated.

“One of the other things my patients usually tell me is that they get a lot of constipation. We are very good with our supportive medications regarding nausea and vomiting management,” he explained. “But still, some of the side effects of the supportive medications which we give, are constipation. So, making sure they are well-hydrated and not constipated will help them go through this treatment phase. There has been a lot of evidence coming out from randomized clinical trials that administrating neoadjuvant chemotherapy actually leads to better survival outcomes. So, they should strongly consider it as compared to directly going for surgery.”

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