Cancer vaccines: The hope is real

Traditionally, vaccines have been used for the protection against infectious diseases, but the focus today has expanded to include the treatment of neoplastic diseases.

"The immune system tends to tolerate cancer cells just as it tolerates normal cells, because it doesn't recognize cancer cells as something foreign," said Steven Hirschfeld, M.D., a medical officer in the Food & Drug Administration's Center for Biologics Evaluation and Research. Rather, cancer cells are once-normal cells that have gone awry. "Cancer vaccines try to get the immune system to overcome its tolerance of cancer cells so that it can recognize and attack them," explained Hirschfeld.

Targeting leukemia and the prostate

"The vaccine was given to 53 leukemia patients with active disease, and 13 in remission when they entered the trial," said Muzaffar Qazilbash, M.D., associate professor at University of Texas M.D. Anderson Cancer Center's Department of Stem Cell Transplantations and Cellular Therapy, and study co-author. All patients had received standard therapy previously, and although some were in remission, none was a good candidate for continued standard treatment because all had advanced disease. In the study, patients whose immune system responded to the peptide vaccine experienced more than three times longer event-free survival than non-responders (8.7 months vs. 2.4 months).

The 13 patients in remission fared the best, with four remaining in remission for a median of 30.5 months. "Immunotherapy works the best for low level of disease," Quazilbash explained, "so patients with low leukemia burden may get the maximum benefit."

Two cell-based prostate cancer vaccines, sipuleucel-T (Provenge, Dendreon) and GVAX (Cell Genesys), are currently in advanced clinical trials.

Dendreon Corp. suffered a setback in May 2007 when the FDA threw up a roadblock to the approval of Provenge. Against the recommendation of its Cellular, Tissue, and Gene Therapies Advisory Committee, the FDA requested additional clinical data to support the efficacy claims in the application for Provenge.

The FDA's decision surprised many clinicians, who view the situation with Provenge as an example of how failing to power a trial for survival can hinder FDA approval. However, patients treated with Provenge did live an average of four-and-a-half months longer than those on the standard treatment-a length of time considered significant for most cancer patients. Dendreon is hoping to receive approval after submitting the results of a larger trial that is designed to measure survival in men with metastatic hormone-refractory prostate cancer, but the final data likely won't be available until 2010.

There seems to be more encouraging news for GVAX. An interim analysis, performed by the Independent Data Monitoring Committee, supported continuation of the VITAL-1 Phase III trial of GVAX for prostate cancer. VITAL-1, a randomized trial designed to compare GVAX with standard treatment in hormone-refractory prostate cancer, has a primary endpoint of improvement in survival. "We can currently estimate that the required number of events needed to conduct the final analysis will be reached in the second half of 2009," said Robert Dow, MBChB, chief medical officer of Cell Genesys, San Francisco.

In a review of prostate cancer vaccine trials published in Clinical Cancer Research in 2007, Jeffrey Schlom, Ph.D., laboratory chief, Laboratory of Tumor Immunology and Biology at the National Cancer Institute (NCI), explained that "perhaps the most unique feature of cancer vaccine therapy is the fact that a vaccine initiates a dynamic process of host immune responses that may be exploited in subsequent therapies." Randomized clinical trials in prostate cancer, conducted at NCI, have offered the same striking evidence that patients who receive vaccine and mount immune responses to the vaccine may have enhanced outcome to subsequent chemotherapy or hormone treatment.