Edwin M Posadas

Publications of Edwin M Posadas

• A phase II trial of gemcitabine, capecitabine, and bevacizumab in metastatic renal carcinoma.

  Authors: Elizabeth K Chung, Edwin M Posadas, Kristen Kasza, Theodore Karrison, Elizabeth Manchen, Olwen M Hahn, Walter M Stadler

  American journal of clinical oncology. 04/2011; 34(2):150-4.

  Renal cancer is resistant to most DNA and DNA repair targeted chemotherapy; although moderate response rates to nucleotide analog based therapy have been reported. Bevacizumab also has activity. WeRenal cancer is resistant to most DNA and DNA repair targeted chemotherapy; although moderate response rates to nucleotide analog based therapy have been reported. Bevacizumab also has activity. We thus performed a phase II trial of gemcitabine, capecitabine, and bevacizumab in patients with metastatic renal cancer. Following significant hematotoxicity, dosing was modified to gemcitabine 1000 mg/m (Days 1, 8), capecitabine 1000 mg twice daily (Days 1-14), and bevacizumab 15 mg/kg (Day 1) on a 21-day cycle with evaluation every 3 cycles. Primary end point was objective response rate. Twenty-nine patients were enrolled between March 2005 and May 2008. Most patients had been previously treated with a vascular endothelial growth factor receptor tyrosine kinase inhibitor. Seven patients (24%) had a partial response. Median overall and progression-free survival were 9.8 months (95% confidence interval: 6.2, 14.9) and 5.3 months (95% confidence interval: 3.9, 9.9), respectively. The regimen was well tolerated with hematologic toxicity, fatigue, and rash being most common. The trial was terminated early despite not meeting criteria for success or futility because of slow accrual and because the historical response rate became irrelevant with emerging data using sequential vascular endothelial growth factor therapies. Nevertheless, the observed progression-free and overall survival compare favorably to other phase II trials in this heavily pretreated population.

• Fyn is downstream of the HGF/MET signaling axis and affects cellular shape and tropism in PC3 cells.

  Authors: Ana R Jensen, Saito Y David, Chuanhong Liao, Jinlu Dai, Evan T Keller, Hikmat Al-Ahmadie, Kelly Dakin-Haché, Peter Usatyuk, Margarit F Sievert, Gladell P Paner, Soheil Yala, Gustavo M Cervantes, Viswanathan Natarajan, Ravi Salgia, Edwin M Posadas

  Clinical cancer research : an official journal of the American Association for Cancer Research. 03/2011; 17(10):3112-22.

  Fyn is a member of the Src family of kinases that we have previously shown to be overexpressed in prostate cancer. This study defines the biological impact of Fyn inhibition in cancer using a PC3Fyn is a member of the Src family of kinases that we have previously shown to be overexpressed in prostate cancer. This study defines the biological impact of Fyn inhibition in cancer using a PC3 prostate cancer model. Fyn expression was suppressed in PC3 cells using an shRNA against Fyn (PC3/FYN-). Knockdown cells were characterized using standard growth curves and time-lapse video microscopy of wound assays and Dunn Chamber assays. Tissue microarray analysis was used to verify the physiologic relevance of the HGF/MET axis in human samples. Flank injections of nude mice were performed to assess in vivo growth characteristics. HGF was found to be sufficient to drive Fyn-mediated events. Compared to control transductants (PC3/Ctrl), PC3/FYN- showed a 21% decrease in growth at 4 days (P = 0.05). PC3/FYN- cells were 34% longer than control cells (P = 0.018) with 50% increase in overall surface area (P < 0.001). Furthermore, when placed in a gradient of HGF, PC3/FYN- cells showed impaired directed chemotaxis down an HGF gradient in comparison to PC3/Ctrl (P = 0.001) despite a 41% increase in cellular movement speed. In vivo studies showed 66% difference of PC3/FYN- cell growth at 8 weeks using bidimensional measurements (P = 0.002). Fyn plays an important role in prostate cancer biology by facilitating cellular growth and by regulating directed chemotaxis-a key component of metastasis. This finding bears particular translational importance when studying the effect of Fyn inhibition in human subjects.

• Editorial comment.

  Authors: Peter H O'Donnell, Edwin M Posadas

  Urology. 01/2011; 77(1):165-6.

• Renal medullary-like carcinoma in an adult without sickle cell hemoglobinopathy.

  Authors: Peter H O'Donnell, Ana Jensen, Edwin M Posadas, Julia A Bridge, Anjana V Yeldandi, Ximing J Yang, Walter M Stadler, Hikmat Al-Ahmadie

  Nature reviews. Urology. 02/2010; 7(2):110-4.

  A 42-year-old white man with no significant prior medical history presented with macroscopic hematuria of 2 months' duration. His family history was notable for a maternal grandfather with kidneyA 42-year-old white man with no significant prior medical history presented with macroscopic hematuria of 2 months' duration. His family history was notable for a maternal grandfather with kidney cancer. Urinalysis, CT, microscopic examination of tumor, immunohistochemical analysis of tumor, hemoglobin electrophoresis, molecular cytogenetic analysis, gene sequencing. Renal medullary-like carcinoma in an adult without sickle cell trait, sickle cell disease or other hemoglobinopathies. The patient underwent laparoscopic nephrectomy to remove the tumor and received adjuvant sorafenib (400 mg per day) as part of the E2805 ASSURE (Adjuvant Sorafenib or Sunitinib for Unfavorable Renal Carcinoma) trial. Metastatic recurrence of the tumor occurred 9 months after nephrectomy, for which the patient underwent tumor debulking and retroperitoneal lymph node dissection, followed by chemotherapy consisting of gemcitabine (2,000 mg/m(2)) and doxorubicin (50 mg/m(2)), both given on day 1 of a 14-day cycle. After six cycles of drug treatment, the patient had achieved a partial response. The patient was managed by active surveillance for 4 months, when he developed further symptoms and disease progression was detected. Third-line systemic therapy in the form of 21-day cycles of cisplatin (80 mg/m(2) on day 1) and etoposide (100 mg/m(2) on days 1-3) has recently been initiated.

• Fyn: a novel molecular target in cancer.

  Authors: Yoshihito D Saito, Ana R Jensen, Ravi Salgia, Edwin M Posadas

  Cancer. 02/2010; 116(7):1629-37.

  Fyn is 59-kDa member of the Src family of kinases that is historically associated with T-cell and neuronal signaling in development and normal cellular physiology. Whereas Src has been heavilyFyn is 59-kDa member of the Src family of kinases that is historically associated with T-cell and neuronal signaling in development and normal cellular physiology. Whereas Src has been heavily studied in cancer, less attention has been traditionally awarded to the other Src kinases such as Fyn. Our group has shown that Fyn is particularly upregulated in prostate cancer in contrast to the alternative members of the Src family. This suggests that it may mediate several important processes attributed to Src kinases in prostate cancer and other malignancies. These functions include not only cellular growth and proliferation but also morphogenesis and cellular motility. Together, these suggest a role for Fyn in both progression and metastasis. As several agents in clinical development affect Fyn activation, understanding the role that Fyn plays in cancer is of great importance in oncology. Cancer 2010. (c) 2010 American Cancer Society.

• Pazopanib: therapeutic developments.

  Authors: Suwicha Limvorasak, Edwin M Posadas

  Expert opinion on pharmacotherapy. 12/2009; 10(18):3091-102.

  Pazopanib (Votrient, GW786034) is a potent pan-VEGF inhibitor in advanced clinical development. Like other orally available VEGFR inhibitors, pazopanib is clinically efficacious and well tolerated.Pazopanib (Votrient, GW786034) is a potent pan-VEGF inhibitor in advanced clinical development. Like other orally available VEGFR inhibitors, pazopanib is clinically efficacious and well tolerated. The recently reported Phase III clinical trial in metastatic renal cell carcinoma showed activity similar to approved agents with variations in toxicity which has led to its recent FDA approval. Given the growing number of agents in this category, differences not only in single-agent activity but also toxicity and combinatorial potency will probably distinguish pazopanib from other similar agents.

• Phase II Trial of Carboplatin and Paclitaxel in Papillary Renal Cell Carcinoma.

  Authors: Kathryn A Bylow, Michael B Atkins, Edwin M Posadas, Walter M Stadler, David F McDermott

  Clinical genitourinary cancer. 02/2009; 7(1):39-42.

  Background: Cytotoxic chemotherapy has not been well investigated in non-clear-cell renal cell carcinoma (RCC). A phase II study was thus conducted to assess the efficacy of carboplatin andBackground: Cytotoxic chemotherapy has not been well investigated in non-clear-cell renal cell carcinoma (RCC). A phase II study was thus conducted to assess the efficacy of carboplatin and paclitaxel in such patients. Patients and Methods: Patients were treated with carboplatin (area under the curve of 6) and paclitaxel 225 mg/m2 every 21 days and assessed for measurable disease response every 2 cycles. An initial 20 patients were planned to be enrolled to rule out a null hypothesized 15% response rate. Results: Seventeen patients were enrolled, of which 16 patients had papillary and 1 had collecting duct histology. The patient with collecting duct histology had a complete response, but no responses were observed in patients with papillary histology and the trial was thus terminated early. Toxicities were as expected for the carboplatin and paclitaxel regimen. Conclusion: Carboplatin and paclitaxel is not an active regimen in patients with metastatic papillary RCC. Future studies should explore the role of this or similar regimens in collecting duct carcinoma.

• FYN is overexpressed in human prostate cancer.

  Authors: Edwin M Posadas, Hikmat Al-Ahmadie, Victoria L Robinson, Ramasamy Jagadeeswaran, Kristen Otto, Kristen E Kasza, Maria Tretiakov, Javed Siddiqui, Kenneth J Pienta, Walter M Stadler, Carrie Rinker-Schaeffer, Ravi Salgia

  BJU international. 11/2008;

  OBJECTIVE To test the hypothesis that FYN, a member of the SRC family of kinases (SFKs), is up-regulated in prostate cancer, as FYN is functionally distinct from other SFKs, and interacts with FAKOBJECTIVE To test the hypothesis that FYN, a member of the SRC family of kinases (SFKs), is up-regulated in prostate cancer, as FYN is functionally distinct from other SFKs, and interacts with FAK and paxillin (PXN), regulators of cell morphology and motility. MATERIALS AND METHODS Through data-mining in Oncomine (http://www.oncomine.org), cell-line profiling with immunoblotting, quantitative reverse transcription and polymerase chain reaction (RT-PCR) and immunohistochemical analysis, we described FYN expression in prostate cancer. The analysis included 32 cases of prostate cancer, nine of prostatic intraepithelial neoplasia (PIN) and 19 normal prostates. Samples were scored for the percentage of stained glands and intensity of staining (from 0 to 3). Each sample was assigned a composite score generated by multiplying percentage and intensity. RESULTS Data-mining showed an eight times greater FYN expression in prostate cancer than in normal tissue; this was specific to FYN and not present for other SFKs. Expression of FYN in prostate cancer cell lines (LNCaP, 22Rv1, PC3, DuPro) was detected using quantitative RT-PCR and immunoblotting. Expression of FYN and its signalling partners FAK and PXN was detected in human tissue. Comparing normal with cancer samples, there was a 2.1-fold increase in median composite score for FYN (P < 0.001) 1.7-fold increase in FAK (P < 0.001), and a doubling in PXN (P < 0.05). There was a 1.7-fold increase in FYN (P < 0.05) and a 1.6-fold increase in FAK (P < 0.01) in cancer compared with PIN. CONCLUSIONS These studies support the hypothesis that FYN and its related signalling partners are up-regulated in prostate cancer, and support further investigation into the role of the FYN as a therapeutic target.

• Combination targeted therapy with sorafenib and bevacizumab results in enhanced toxicity and antitumor activity.

  Authors: Nilofer S Azad, Edwin M Posadas, Virginia E Kwitkowski, Seth M Steinberg, Lokesh Jain, Christina M Annunziata, Lori Minasian, Gisele Sarosy, Herbert L Kotz, Ahalya Premkumar, Liang Cao, Deborah McNally, Catherine Chow, Helen X Chen, John J Wright, William D Figg, Elise C Kohn

  Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 08/2008; 26(22):3709-14.

  PURPOSE: Sorafenib inhibits Raf kinase and vascular endothelial growth factor (VEGF) receptor. Bevacizumab is a monoclonal antibody targeted against VEGF. We hypothesized that the complementaryPURPOSE: Sorafenib inhibits Raf kinase and vascular endothelial growth factor (VEGF) receptor. Bevacizumab is a monoclonal antibody targeted against VEGF. We hypothesized that the complementary inhibition of VEGF signaling would have synergistic therapeutic effects. PATIENTS AND METHODS: Patients had advanced solid tumors, Eastern Cooperative Oncology Group performance status of 0 to 1, and good end-organ function. A phase I dose-escalation trial of sorafenib and bevacizumab was initiated at below-recommended single-agent doses because of possible overlapping toxicity: sorafenib 200 mg orally twice daily and bevacizumab intravenously at 5 mg/kg (dose level [DL] 1) or 10 mg/kg (DL2) every 2 weeks. Additional patients were enrolled at the maximum-tolerated dose (MTD). RESULTS: Thirty-nine patients were treated. DL1 was the MTD and administered in cohort 2 (N = 27). Dose-limiting toxicity in DL2 was grade 3 proteinuria and thrombocytopenia. Adverse events included hypertension, hand-foot syndrome, diarrhea, transaminitis, and fatigue. Partial responses (PRs) were seen in six (43%) of 13 patients with ovarian cancer (response duration range, 4 to 22+ months) and one of three patients with renal cell cancer (response duration, 14 months). PR or disease stabilization >or= 4 months (median, 6 months; range, 4 to 22+ months) was seen in 22 (59%) of 37 assessable patients. The majority (74%) required sorafenib dose reduction to 200 mg/d at a median of four cycles (range, one to 12 cycles). CONCLUSION: Combination therapy with sorafenib and bevacizumab has promising clinical activity, especially in patients with ovarian cancer. The rapidity and frequency of sorafenib dose reductions indicates that sorafenib at 200 mg twice daily with bevacizumab 5 mg/kg every 2 weeks may not be tolerable long term, and alternate sorafenib dosing schedules should be explored.

• A prospective analysis of imatinib-induced c-KIT modulation in ovarian cancer: a phase II clinical study with proteomic profiling.

  Authors: Edwin M Posadas, Virginia Kwitkowski, Herbert L Kotz, Virginia Espina, Lori Minasian, Nana Tchabo, Ahalya Premkumar, Mahrukh M Hussain, Richard Chang, Seth M Steinberg, Elise C Kohn

  Cancer. 07/2007; 110(2):309-17.

  BACKGROUND: c-Kit and platelet-derived growth factor receptor (PDGFR) are potential molecular targets in epithelial ovarian cancer (EOC). Imatinib inhibits the kinase domain and subsequent downstreamBACKGROUND: c-Kit and platelet-derived growth factor receptor (PDGFR) are potential molecular targets in epithelial ovarian cancer (EOC). Imatinib inhibits the kinase domain and subsequent downstream signaling of these receptor tyrosine kinases. The objective of this study was to investigate biochemical and biologic effects of imatinib on EOC. METHODS: Patients with recurrent EOC who had received no more than 4 prior regimens and who had good end-organ function were eligible. Imatinib was administered orally at a dose of 400 mg twice daily in continuous, 28-day cycles with reassessment imaging studies obtained every other cycle. Tumor core biopsies were obtained prior to and at 4 weeks into therapy; microdissected tumor and stroma were subjected to protein lysate array analysis. Blood samples were obtained monthly for cytokine measurements. RESULTS: Twenty-three patients were enrolled, including 16 patients who received imatinib 600 mg daily because of gastrointestinal (GI) toxicity and fluid accumulation at the starting dose. The median time to disease progression was 2 months (range, 2-14 months). Common grade 3 toxicities included edema/ascites/pleural effusions in 11 patients (48%), GI complaints in 8 patients (35%), fatigue in 3 patients (13%), and grade 2 and 3 cytopenias in 10 patients and 3 patients (43% and 13%), respectively. Increased circulating levels of interleukin 6 were associated with grade >/=2 fluid collection (P = .02). A statistically significant trend was observed between pretreatment phosphorylated-kit levels in microdissected tumor and stroma and GI toxicity (P < .01), between tumor levels of epidermal growth factor receptor (EGFR) and PDGFR with grade of fatigue (P </= .005), and EGFR and phosphorylated-AKT levels with grade of ascites and edema (P </= .01). CONCLUSIONS: The results of this study indicated imatinib had minimal activity as a single agent in EOC. Its ability to modulate its molecular targets suggests that it may be considered in combinatorial therapy.

• A phase II study of ixabepilone (BMS-247550) in metastatic renal-cell carcinoma.

  Authors: Edwin M Posadas, Samir Undevia, Elizabeth Manchen, James L Wade, A Dimitrios Colevas, Theodore Karrison, Everett E Vokes, Walter M Stadler

  Cancer biology & therapy. 05/2007; 6(4):490-3.

  INTRODUCTION: Ixabepilone (BMS-247550) is a semi-synthetic analog of epothilone B that has been characterized as a microtubule stabilizing agent with a mechanism of action distinct from taxanes.INTRODUCTION: Ixabepilone (BMS-247550) is a semi-synthetic analog of epothilone B that has been characterized as a microtubule stabilizing agent with a mechanism of action distinct from taxanes. Suggestion of activity in renal cell carcinoma (RCC) has been seen in early clinical studies. METHODS: Eligible patients had metastatic RCC as well as ECOG performance status 0-2 and normal organ function. Patients received ixabepilone at a dose of 40 mg/m2 intravenously over three hours every 21 days. There was no restriction on RCC histology or prior treatment type, but prior treatment with tubule inhibitors was not allowed. The primary endpoint was RECIST defined response and radiographic evaluations were performed every three cycles. Toxicity evaluations utilized CTCAE v3.0 and were performed every cycle. Using a Simon two-stage optimal design with alpha = 0.1, beta = 0.1, a null hypothesized response rate of 0.05 and an alternative response rate of 0.2, an initial 12 patients were to be accrued with full accrual of 37 patients if at least one response were observed. RESULTS: A median of five cycles were administered. No objective responses were observed in the first 12 evaluable patients, and six patients showed stable disease for more than 18 weeks on therapy. Median time to progression among those with objective progression was nine weeks. One patient experienced grade 4 anemia and lymphopenia. Grade 3 adverse events included lymphopenia, neutropenia, leukopenia, diarrhea, and infection. Common grade 2 toxicities included alopecia, fatigue and anemia. CONCLUSION: Ixabepilone administered at a dose of 40 mg/m2 every 21 days should not be advanced for further study in metastatic RCC. Given previous results, however, other dosing schedules may be worthy of further investigation.

• A phase II and pharmacodynamic study of gefitinib in patients with refractory or recurrent epithelial ovarian cancer.

  Authors: Edwin M Posadas, Meghan S Liel, Virginia Kwitkowski, Lori Minasian, Andrew K Godwin, Mahrukh M Hussain, Virginia Espina, Bradford J Wood, Seth M Steinberg, Elise C Kohn

  Cancer. 04/2007; 109(7):1323-30.

  BACKGROUND: The primary objective of this study was to evaluate the biochemical effects of gefitinib on its target signal-transduction pathways in patients with recurrent epithelial ovarian cancerBACKGROUND: The primary objective of this study was to evaluate the biochemical effects of gefitinib on its target signal-transduction pathways in patients with recurrent epithelial ovarian cancer (EOC). The secondary objectives included assessing clinical activity and toxicity and determining the association between biochemical and clinical outcomes. METHODS: Twenty-four heavily pretreated patients with EOC who had good end-organ function and performance status and who had measurable disease received gefitinib 500 mg daily. Prospectively planned core-needle tumor biopsies were obtained before treatment and after 4 weeks. Protein expression of total and phosphorylated (p) epidermal growth factor receptor (EGFR), protein kinase B (AKT), and extracellular regulated kinase (ERK) was quantified in microdissected tumor cells using tissue lysate array proteomics. RESULTS: All tumor samples had detectable levels of EGFR and p-EGFR. A decrease in the quantity of both EGFR and p-EGFR was observed with gefitinib therapy in >50% of patients. This was not associated with clinical benefit, nor were responses observed. However, trends for increased gastrointestinal and skin toxicity were observed with greater phosphorylation or quantities of EGFR, ERK, and AKT in tumor samples (P </= .05). Gefitinib had limited clinical activity as monotherapy despite documented target inhibition. CONCLUSIONS: The results from this study demonstrated that gefitinib inhibited the phosphorylation of EGFR in EOC tumor cells, providing proof of target in a clinical setting. Combinatorial therapy with molecular therapeutics against complementary targets may prove successful.

• A phase II study of perifosine in androgen independent prostate cancer.

  Authors: Edwin M Posadas, James Gulley, Philip M Arlen, Alisa Trout, Howard L Parnes, John Wright, Min-Jung Lee, Eun Joo Chung, Jane B Trepel, Alex Sparreboom, Clara Chen, Elizabeth Jones, Seth M Steinberg, Andrew Daniels, William D Figg, William L Dahut

  Cancer biology & therapy. 11/2005; 4(10):1133-7.

  OBJECTIVES: Perifosine is an alkylphospholipid that has exhibited broad antineoplastic activity in preclinical studies. The primary objective of this study was to determine the clinical efficacy ofOBJECTIVES: Perifosine is an alkylphospholipid that has exhibited broad antineoplastic activity in preclinical studies. The primary objective of this study was to determine the clinical efficacy of this agent in the treatment of androgen-independent prostate cancer (AIPC) using PSA and clinical criteria. PATIENTS AND METHODS: Nineteen patients with progressive, metastatic AIPC were treated with oral perifosine. Cycles were 28 days in length. A loading dose of 900 mg was given on day 1 of cycle 1 followed by a maintenance dose of 150 mg daily for the next 20 days. A loading dose of 600 mg was administered on the first day of subsequent cycles by the maintenance dose of 150 mg daily for the next 20 days. Pharmacokinetic measurements were made throughout the course of the study. Circulating epithelial cells were collected via leukapheresis on day 0, 3, and 28. RESULTS: Median patient age was 67 years and median PSA was 180 ng/mL (range: 19-904 ng/ml). Grade 1-2 fatigue and gastrointestinal toxicities were common. Pharmacokinetic studies showed an average minimum concentration at steady-state of approximately 4059 ng/ml which correlated well with previous studies. Median time to progression was four weeks. There were no radiographic responses or PSA declines of 50% or greater related to perifosine. CONCLUSIONS: Treatment with perifosine was complicated by fatigue and gastrointestinal toxicity. No significant clinical activity against prostate cancer was observed. This agent does not merit further study in the setting of monotherapy in this population.

• Proteomics and ovarian cancer: implications for diagnosis and treatment: a critical review of the recent literature.

  Authors: Edwin M Posadas, Ben Davidson, Elise C Kohn

  Current opinion in oncology. 10/2004; 16(5):478-84.

  PURPOSE OF REVIEW: Epithelial ovarian cancer is the leading cause of death from gynecologic malignancies amongst American women. Emerging proteomic technologies have promise for early diagnosis andPURPOSE OF REVIEW: Epithelial ovarian cancer is the leading cause of death from gynecologic malignancies amongst American women. Emerging proteomic technologies have promise for early diagnosis and in advancing treatment directions. Application of these technologies has produced new biomarkers, diagnostic approaches, and understanding of disease biology. RECENT FINDINGS: Mass spectral blood and tissue analysis has yielded new putative biomarkers that require further validation and assessment of diagnostic specificity and sensitivity. Protein signature patterns derived from mass spectrometry datastreams have been modeled and are moving into validation. Tissue-based protein analysis has led to identification of tumor and stromal protein and signal activation events in ovarian cancer. Clinical trials are now ascertaining tissue samples prior to and during therapy with molecularly targeted agents to evaluate modulation of targeted signaling pathways. Finally, proteomic analysis of tissues and metastases will outline biochemical events underlying the metastatic phenotype of ovarian cancer. SUMMARY: Proteomic approaches are experimental technologies applied to ovarian and other cancers. Proper validation and use of findings may advance our understanding of biochemical events that have complicated successful detection and intervention. This knowledge is the first step in fulfilling the promise of personalized molecular medicine.

• Approaches to inhibit invasiveness and metastasis in prostate cancer.

  Authors: Edwin M Posadas, William L Dahut

  Clinical prostate cancer. 10/2002; 1(2):125.

• The emerging role of bisphosphonates in prostate cancer.

  Authors: Edwin M Posadas, William L Dahut, James Gulley

  American journal of therapeutics. 11(1):60-73.

  Bisphosphonates are a class of therapeutic agents originally designed to treat loss of bone density. It has been shown that the primary mechanism of action is inhibition of osteoclastic activity.Bisphosphonates are a class of therapeutic agents originally designed to treat loss of bone density. It has been shown that the primary mechanism of action is inhibition of osteoclastic activity. Accumulating data show that these drugs are useful in diseases with propensities toward osseous metastases. In particular, they are effective in diseases in which there is clear upregulation of osteoclastic or osteolytic activity such as breast cancer and multiple myeloma. Despite the fact that osseous metastases in prostate cancer manifest as osteosclerosis rather than osteolysis, studies now show that bisphosphonates are useful in the management of this disease. In particular, they have demonstrated an impact on osteoporosis associated with hormonal therapy, bone pain from metastases, and skeleton-related events from prostatic adenocarcinoma. This review briefly summarizes the available clinical data on the utilization of bisphosphonates in the disease of prostate cancer.