MVAC Still the ‘Best Treatment’ for Advanced Bladder Cancer Patients

CHICAGO—Despite recent excitement about therapy involving ifosfamide (Ifex) and other new chemotherapy drug combinations, MVAC—methotrexate, vinblastine, Adriamycin (doxorubicin), and cisplatin—remains the standard of care for advanced bladder cancer, Derek Raghavan, MD, said at the Chicago Prostate Cancer Shootout III Plus Bladder Conference, sponsored by the Chicago Urological Society, Chicago Radiological Society, and Chicago Medical Society

Dr. Raghavan, chief of medical oncology, University of Southern California Norris Cancer Center, acknowledged that some of the newer drug combinations may be less toxic than MVAC, but they do not significantly increase survival over that achieved with MVAC and may produce significantly worse survival results.

MVAC has been considered the standard for treating advanced bladder cancer since 1992 when it was tested against cisplatin in 600 patients and demonstrated a significant doubling in median survival. However, the MVAC combination is extremely toxic and achieves a median survival of only 12.5 to 13.4 months, Dr. Raghavan said.

Although replacing the highly toxic MVAC regimen with one that has fewer severe adverse side effects is a laudable goal, he wondered, “Are these new combinations good enough in terms of survival?”

In a phase II trial at Memorial Sloan-Kettering Cancer Center that included many patients with lymph node metastases, the ITP combination (ifosfamide, paclitaxel [Taxol], and platinum) yielded an impressive median survival of 18 months.

Concerned that these results may represent stage migration, Dr. Raghavan said that before “we switch from MVAC to ITP, we should be requiring that Sloan-Kettering or somebody else do the randomized trial that asks the question: Is ITP better than MVAC? My hunch is that ITP will be better, but not in terms of better survival; it will just be less toxic. This is an important endpoint, but it is not the same as saying ITP is a gigantic leap forward.”

Results of a phase II trial of paclitaxel plus carboplatin, conducted at Wayne State University, created enthusiasm because of its reduced toxicity, “but it is not a regimen I want to use routinely,” Dr. Raghavan said, because of its median survival of only 9.5 months.

Use of Gemcitabine

The “other new kid on the block”—gemcitabine (Gemzar)—is an interesting drug for bladder cancer because of early results from a 1997 clinical trial, Dr. Raghavan said. Median survival was 14 months when gemcitabine was given with cisplatin in a small multicenter study that included 47 patients with positive lymph nodes and visceral disease.

Since then, he said, gemcitabine has been used in conjunction with other chemotherapeutic agents in patients with metastatic bladder cancer.

When used with paclitaxel and carboplatin, gemcitabine had a high response rate (17 of 29 patients had a partial response), but no clear survival data have emerged from that trial. Gemcitabine is being added to ITP along with doxorubicin in further tests at Memorial Sloan-Kettering.

Because gemcitabine by itself or in combination with other chemotherapy agents is not as toxic as the MVAC regimen, it may prove to be an effective treatment alternative. “If survival data from gemcitabine plus cisplatin are comparable to those with MVAC, then we may have a new standard of care. If not, we’re back to square one,” Dr. Raghavan commented.