Castration Resistant, Taxane Naïve Metastatic Prostate Cancer: Current Clinical Approaches and Future Directions

Gignac, Gretchen A.; Morris, Michael J.; Hussain, Maha

doi:10.1016/j.juro.2007.04.033

« Previous Next »The Journal of Urology
Volume 178, Issue 3, Supplement , Pages S30-S35, September 2007

Castration Resistant, Taxane Naïve Metastatic Prostate Cancer: Current Clinical Approaches and Future Directions

Gretchen A. Gignac
- Genitourinary Oncology Service, Department of Medicine, and Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan-Kettering Cancer Center, New York, New York
- Department of Medicine, Joan and Sanford E. Weill College of Medicine of Cornell University, New York, New York
Michael J. Morris
- Genitourinary Oncology Service, Department of Medicine, and Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan-Kettering Cancer Center, New York, New York
- Department of Medicine, Joan and Sanford E. Weill College of Medicine of Cornell University, New York, New York
- Correspondence: Genitourinary Oncology Service, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., Box 444, New York, New York 10021 (telephone: 646-422-4469; FAX: 212-988-0701).
- Financial interest and/or other relationship with Sanofi Aventis, Cytogen and Agensys.
Maha Hussain
- Departments of Medicine and Urology, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan
- Financial interest and/or other relationship with Merck.

published online 18 July 2007.

Purpose

With the wide use of prostate specific antigen to detect response and disease progression resistance to androgen deprivation is being detected at an increasingly earlier stage. We focused on the current management and novel investigational strategies for the chemonaïve patient population with castration resistant metastatic disease.

Materials and Methods

We reviewed standard and investigational hormonal, chemotherapeutic, biological and immune based strategies for patients with castration resistant metastatic prostate cancer who have not yet received taxane based chemotherapy.

Results

Our understanding of the natural history of this group of patients is evolving. A variety of standard and experimental treatment options are available for this group of patients. Manipulating the androgen receptor signaling axis, targeting antiapoptotic pathways, using antiangiogenic strategies, harnessing the immune system and optimizing docetaxel based regimens and novel cytotoxic agents are under investigation.

Conclusions

Multiple agents currently under development offer a promise of palliation and prolongation of survival above and beyond that of docetaxel. In the absence of guidance from randomized trials with regard to chemotherapy timing, and considering the modest effects of docetaxel on survival, decisions regarding choice of therapy (standard chemotherapy or experimental therapies) must be based on careful consideration of the functional status of each individual, presence of symptoms, comorbidities and overall therapeutic objectives.

Key Words: prostate, prostatic neoplasms, drug therapy, immunotherapy, receptors, androgen

Abbreviations and Acronyms: AR, androgen receptor, CALGB, Cancer and Leukemia Group B, CTLA4, cytotoxic T lymphocyte-associated antigen 4, ET-1, endothelin 1, HDAC, histone deacetylase, Hsp90, heat shock protein 90, PSA, prostate specific antigen, RANK, receptor activator of nuclear factor-κB, VEGF, vascular endothelial growth factor