A randomized phase II study of concurrent docetaxel plus vaccine versus vaccine alone in metastatic androgen-independent prostate cancer.

Abstract

Purpose: Docetaxel has activity against androgen-independent prostate cancer and preclinical studies have shown that taxane-based chemotherapy can enhance antitumor response of vaccines. The primary objective of this study was to determine if concurrent docetaxel (with dexamethasone) had any effect on generating animmune responseto the vaccine. Secondary endpoints were whether vaccine could be given safely with docetaxel and the clinical outcome of the treatment regimen. Experimental Design: The vaccination regimen was composed of (a) recombinant vaccinia virus (rV) that expresses the prostate-specific antigen gene (rV-PSA) admixed with (b) rV that expresses the B7.1 costimulatory gene (rV-B7.1), and (c) sequential booster vaccinations with recombinant fowlpox virus (rF-) containing the PSA gene (rF-PSA). Patients received granulocyte macrophage colony-stimulating factor with each vaccination. Twenty-eight patients with metastatic androgen-independent prostate cancer were randomized to receive either vaccine and weekly docetaxel or vaccine alone. Patients on the vaccine alone arm were allowed to cross over to receive docetaxel alone at time of disease progression. The ELISPOT assay was used to monitor immune responses for PSA-specificTcells. Results: The median increase in these T-cell precursors to PSA was 3.33-fold in both arms following 3 months of therapy. In addition, immune responses to other prostate cancerâ ssociated tumor antigens were also detected postvaccination. Eleven patients who progressed on vaccine alone crossed over to receive docetaxel at time of progression. Median progressionfree survival on docetaxel was 6.1months after receiving vaccine compared with 3.7 months with the same regimen in a historical control. Conclusion: This is the first clinical trial to show that docetaxel can be administered safely with immunotherapy without inhibiting vaccine specific T-cell responses. Furthermore, patients previously vaccinated with an anticancer vaccine may respond longer to docetaxel compared with a historical control of patients receiving docetaxel alone. Larger prospective clinical studies will be required to validate these findings.Adenocarcinoma of the prostate is the most common noncutaneous malignancy diagnosed in American males and the second leading cause of cancer death. One of six men will develop clinically significant prostate cancer in his lifetime.During 2005, an estimated 232,900 men will be diagnosed with prostate cancer and 30,350 will die from the disease in the United States (1). Overall survival for patients with metastatic androgen-independent prostate cancer has been improved with a docetaxel-based regimen. The clinical benefit shown in these recent studies is an f3-month increase in survival using an every-3-week regimen of docetaxel (2, 3). However, compared with the every-3-week schedule, weekly docetaxel is associated with significantly less grade 3 or 4 hematologic toxicity. Other studies have looked at combining weekly docetaxel with other agents (4, 5). A random...

Enhancing efficacy of therapeutic vaccinations by combination with other modalities

“…One phase II clinical study of patients with metastatic AIPC randomized to vaccine alone or vaccine with low-dose docetaxel was recently reported [37]. The vaccine regimen consisted of a priming vaccine with rV-PSA admixed with rV-B7-1, followed by monthly booster vaccines with rF-PSA.…”

Combining vaccines with conventional therapies for cancer

“…27 The vaccine regimen consisted of a priming vaccine with rV-PSA admixed with rV-B7-1, followed by monthly booster vaccines with rF-PSA. The vaccines were given with local GM-CSF.…”

DNA Vaccines for Prostate Cancer

“…Such treatments may include other standard therapies for prostate cancer, such as chemotherapy, radiation therapy, or androgen deprivation, all of which may have effects on tumor antigen presentation and/or can produce an inflammatory tumor micro environment [64–70]. In addition, agents capable of reversing or inhibiting the generation of tolerant/regulatory immune responses that counterbalance the inflammatory immune response elicited by vaccination will be critical.…”