Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2014;16(3):122-30.

The Rationale for Optimal Combination Therapy With Sipuleucel-T for Patients With Castration-resistant Prostate Cancer

Vladimir Mouraviev  1 , Neil Mariados  1 , David Albala  2 , Raoul S Concepcion  2 , Neal D Shore  3 , Robert B Sims  4 , Mark Emberton  5 , Christopher M Pieczonka  1
Affiliations
Review

The Rationale for Optimal Combination Therapy With Sipuleucel-T for Patients With Castration-resistant Prostate Cancer

Vladimir Mouraviev et al. Rev Urol. 2014.

Abstract

Immunotherapy encourages the recipient's own immune response to destroy cancer cells, and current evidence suggests that immunotherapies may be most beneficial in early metastatic castration-resistant prostate cancer (mCRPC). Sipuleucel-T is the first therapeutic cancer vaccine to be approved by both the US Food and Drug Administration and European Medicines Agency for the treatment of asymptomatic or minimally symptomatic mCRPC. Combining immunotherapy with other treatments may have potent anticancer effects; cytoreductive therapies can release tumor antigens and promote a proinflammatory environment that could augment immunotherapies. However, some cytoreductive agents or coadministered drugs may be immunosuppressive. Understanding these interactions between different mCRPC treatment modalities may offer further potential to improve patient outcomes.

Keywords: Combination therapy; Prostate cancer; Sipuleucel-T.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Theoretical growth-moderating effect of (A) immunotherapy or (B) cytoreductive therapy as monotherapies, or (C) in combination. Adapted from Madan RA et al and Schlom J.
Figure 2
Figure 2
The position of sipuleucel-T treatment and other modalities in the natural course of prostate cancer. aApproved indication. ADT, androgen deprivation therapy; CAR, chimeric antigen receptor; Cryo, cryoablation; CRPC, castrate-resistant prostate cancer; HIFU, high-intensity focused ultrasound; IEP, irreversible electroporation; IMRT, intensity-modulated radiation therapy; LHRH, luteinizing hormone-releasing hormone; M0, nonmetastatic; M1, metastatic; PD, programmed death; VPT, vascular photodynamic therapy.
Figure 3
Figure 3
Potential modalities to be used as a combinatorial approach for castration-resistant prostate cancer. Reproduced with permission from Galsky MD et al. CYP17 indicates a cytochrome p450 complex involved in adrenal steroidal synthesis; Met RTK, Met receptor tyrosine kinase; VEGFR2, vascular endothelial growth factor receptor 2; RANKL, receptor activator of nuclear factor k-B ligand; RANK, receptor activator of nuclear factor k-B.
See this image and copyright information in PMC

References

    1. Kusmartsev S, Vieweg J. Enhancing the efficacy of cancer vaccines in urologic oncology: new directions. Nat Rev Urol. 2009;6:540–549. - PubMed
    1. Kirkwood JM, Butterfield LH, Tarhini AA, et al. Immunotherapy of cancer in 2012. CA Cancer J Clin. 2012;62:309–335. - PMC - PubMed
    1. Dendreon Corporation, authors. Sipuleucel-T prescribing information. [Accessed May 2014. 2014].
    1. Higano CS, Schellhammer PF, Small EJ, et al. Integrated data from 2 randomized, double-blind, placebo-controlled, phase 3 trials of active cellular immunotherapy with sipuleucel-T in advanced prostate cancer. Cancer. 2009;115:3670–3679. - PubMed
    1. Kantoff PW, Higano CS, Shore ND, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363:411–422. - PubMed