Alternative to ADT?
Meanwhile, experts are talking about using sipuleucel-T for other indications. Dendreon is conducting a phase III trial of the vaccine in prostate cancer patients who've undergone prostatectomy and whose only sign of recurrence is a rising level of prostate-specific antigen (PSA) in the blood. Launched in 2001 and dubbed PROTECT, the trial should complete data collection from the 159 recruited patients in 10–13 years, according to the company.
"Conceivably, people might use immunotherapy in patients with a rising PSA after local therapy," said Philip Kantoff, M.D., chief of the division of solid tumor oncology at the Dana–Farber Cancer Center and a professor of medicine at Harvard Medical School. He was the principal investigator on the IMPACT trial and continues to work with Dendreon in recruiting patients for other trials. "It would have to be proven."
He also said immunotherapy could be used instead of androgen-deprivation therapy (ADT) or to delay the use of ADT for prostate cancer. "Alternatives to ADT would be welcome because of its [substantial] side effects like lost libido, lost muscle mass, hot flashes, and bone demineralization," he said. "We're all looking for therapies that might delay or avoid the use of ADT."
Many clinicians remain skeptical about using sipuleucel-T as an alternative to ADT for advancing prostate cancer, which is an off-label use that neither Medicare nor private insurers reimburse for. "Even though it isn't that toxic, it is still more aggressive as a treatment than ADT, which everyone knows works," said Peter Albertsen, M.D., a urologist and professor of surgery at the University of Connecticut. "We don't know what the true side-effect profile is, and the side effects for ADT are very modest."
Neuss remains excited about the potential of vaccinelike products in fighting cancers. He speculates that sipuleucel-T's small benefit was due to the antigen chosen for incorporation into dendritic cells. Developers of other immune-system boosters for fighting prostate cancer have chosen different targets. Nordic Immunotherapeutics' Prostvac-VF, tested in a phase II trial and now in phase III testing, consists of two recombinant viral vectors that contain PSA and three immune system–stimulating molecules. Northwest Biotherapeutics' DCVax, which is in a phase III trial for men with nonmetastatic disease, uses prostate-specific membrane antigen as its antigen.
"If you can identify a target that is integral to the survival of the cell, then I think [a vaccine] will be a good product," Neuss said. "This Provenge is close but not quite there yet."