XOFIGO® (Radium Ra 223 dichloride): The FDA on May 15, 2013 approved XOFIGO® Injection for the treatment of castration-resistant prostate cancer patients with symptomatic bone metastases and no known visceral metastatic disease. XOFIGO® is an alpha-particle emitting radiotherapeutic drug. It mimics calcium and forms complexes with hydroxyapatite at sites of increased bone turnover, as seen at metastatic lesions in the bone. XOFIGO® is a product of Bayer HealthCare Pharmaceuticals Inc.
Tag: Prostate Cancer
Proton Versus Intensity-Modulated Radiotherapy for Prostate Cancer Patterns of Care and Early Toxicit
SUMMARY: Proton Radiotherapy (PRT) unlike external beam radiotherapy uses energy from positively charged particles called protons and has the ability to precisely localize the radiation dose to the tumor site, minimizing collateral damage. In this retrospective analysis, data on 27,647 Medicare beneficiaries who received PRT or IMRT (Intensity-Modulated RadioTherapy) for prostate cancer, was reviewed, during 2008 and/or 2009. At 12 months post-treatment, there was no statistical difference in genitourinary and gastrointestinal toxicity for patients who had received PRT compared to those who were treated with IMRT. With PRT almost twice as expensive as IMRT, it remains to be seen if PRT will be reimbursed by third party payors. It is interesting to note that in this study, patients receiving PRT were relatively younger, healthier, and lived in more affluent areas than patients receiving IMRT. Yu JB, Soulos PR, Herrin J, et al. J. Natl. Cancer Inst. 2013;105:25-32
PROTON BEAM RADIATION THERAPY (PBRT) for Prostate Cancer
PBRT is a type of external beam radiation therapy in which a beam of Proton particles are used to irradiate cancer tissue. It has been claimed that the main advantage of proton therapy is its ability to more precisely localize the radiation dosage to the tumor tissue and thereby improve tumor control, without causing significant damage to the surrounding tissues. This theoretical consideration was however disproved in a study published in the Jan 2, 2013 issue of the JNCI. In this study, data was gathered following prostate cancer treatment of over 22,000 medicare beneficiaries, with either IMRT (Intensity Modulated Radiation Therapy) or PBRT. The authors noted that PBRT was not superior to IMRT with regards to efficacy or toxicity, after one year. PBRT was however twice as expensive as IMRT. It therefore remains to be seen if third party payors will warm up to PBRT, with the expansion of PBRT centers across the country.
ZYTIGA® (Abiraterone)
The FDA on December 10, 2012 approved an expanded indication for ZYTIGA® in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer. ZYTIGA® tablets are a product of Janssen Biotech, Inc.
XTANDI® (Enzalutamide)
The FDA on August 31, 2012 approved XTANDI® (Enzalutamide) for the treatment of patients with metastatic castration-resistant prostate cancer who have previously received docetaxel. XTANDI® capsules are a product of Medivation, Inc. and Astellas Pharma US, Inc.
XTANDI® (Enzalutamide) now approved for Late-Stage Prostate Cancer
SUMMARY:The US Food and Drug Administration (FDA) approved XTANDI® (Enzalutamide), an oral agent, formerly known as MDV3100, for men with metastatic castration-resistant prostate cancer who had progressed on TAXOTERE® (Docetaxel) based chemotherapy regimen. The approval was based on the results from the AFFIRM clinical trial. XTANDI® is an androgen receptor antagonist with a significantly higher binding affinity for the androgen receptor (AR) compared to the antiandrogen bicalutamide and there by competitively inhibits the binding of androgens to the androgen receptor. Majority of the patients with advanced prostate cancer become refractory to hormone therapy because of increased production of androgen receptors by the tumors as well as mutated androgen receptors. The superiority of this novel agent, XTANDI®, is based on the fact that the expression of androgen receptor dependent genes are downregulated with XTANDI® leading to cell death or apoptosis, whereas with bicalutamide the expression of these genes are upregulated. Further XTANDI® continues to antagonize mutated androgen receptors on the prostate tumor cells in contrast to bicalutamide which behaves as an agonist. It is thus an androgen receptor signaling inhibitor (ARSI). The AFFIRM clinical trial is a randomized, multinational phase III study in which patients who had received prior docetaxel-based chemotherapy regimens were randomized 2:1 to receive either XTANDI®, 160 mg/day or placebo. Patients treated with XTANDI® had a median survival of 18.4 months, compared with 13.6 months for men treated with placebo, with a median OS advantage of 4.8 months and a reduction in the risk of death by 37%. Scher HI, Fizazi K, Saad F, et al. J Clin Oncol 30, 2012 (suppl 5; abstr LBA1)
Radical Prostatectomy versus Observation for Localized Prostate Cancer
SUMMARY: In this study, 731 men with localized prostate cancer, diagnosed based on PSA testing, were randomly assigned to Radical Prostatectomy (RP) or Observation. The median age was 67 years, median PSA was 7.8ng/ml and median follow up was 10 years. This study concluded that RP did not significantly reduce all cause mortality or mortality related to prostate cancer. However on subset analysis, RP slightly decreased mortality among men with PSA greater than 10ng/ml and among those with intermediate and high D’Amico tumor risk score. As only 10% of the patients were less than 60 years of age, these data may not be applicable to this patient subset. Based on this study, it may be reasonable to avoid RP for those prostate cancer patients with PSA levels of 10ng/ml or less and for those with low risk tumors. Wilt TJ, Brawer MK, Jones KM, et al., for the Prostate Cancer Intervention versus Observation Trial (PIVOT) Study Group. N Engl J Med 2012; 367:203-213
Intermittent (IAD) versus continuous androgen deprivation (CAD) in hormone sensitive metastatic prostate cancer (HSM1PC) patients (pts) Results of S9346 (INT-0162), an international phase III trial
SUMMARY: Preclinical data had suggested that Intermittent Androgen Deprivation (IAD) could prolong response to therapy and alleviate side effects related to androgen deprivation. In this Phase III trial, 3040 enrolled patients with hormone sensitive metastatic prostate cancer, with PSA ≥ 5 ng/ml, were treated for 7 months with ZOLADEX® (Goserelin) plus CASODEX® (Bicalutamide). After 7 months of this combination therapy, 1535 eligible patients achieved a PSA of ≤4.0 ng/ml. These patients were then randomized to either continue ZOLADEX® plus CASODEX® (Continuous Androgen Deprivation -CAD) or receive this combination intermittently (Intermittent Androgen Deprivation – IAD). The primary endpoint was overall survival. The median Overall Survival from the time of randomization in the CAD group was 5.8 years versus 5.1 years for the IAD group. However, a subset analysis surprisingly revealed that patients with minimal metastatic disease had a statistically significant survival advantage with CAD whereas those with extensive metastatic disease had a better survival with IAD. Counter intuitive as it may be, this study has clearly suggested that the choice of CAD versus IAD should be based on the extent of metastatic disease, in patients with hormone sensitive prostate cancer. Hussain M, Tangen CM, Higano CS, et al. J Clin Oncol 2012; 30, 2012 (suppl; abstr 4)
Effect of neoadjuvant abiraterone acetate (AA) plus leuprolide acetate (LHRHa) on PSA, pathological complete response (pCR), and near pCR in localized high-risk prostate cancer (LHRPC) Results of a randomized phase II study
SUMMARY: Abiraterone acetate (ZYTIGA®) is a novel, targeted, oral androgen biosynthesis inhibitor that decreases androgen production in the adrenal glands, testes and prostate cancer cells by inhibiting a steroidal enzyme CYP17. This agent, was approved by the FDA in April, 2011 for use in combination with prednisone, for the treatment of patients with metastatic CRPC (Castrate Resistant Prostate Cancer), who have received prior chemotherapy containing docetaxel (TAXOTERE®). Patients with high risk localized prostate cancer do poorly in spite of aggressive local therapies. To improve outcomes in this patient population, the authors conducted a neoadjuvant trial in which patients with localized prostate cancer with high risk features were divided into two groups. The first group (n = 28) was treated with the LHRH analog, LUPRON® (Leuprolide acetate) for 12 weeks, followed by 12 weeks of combination treatment with LUPRON® and ZYTIGA® . The second group (n = 30) received neoadjuvant LUPRON® plus ZYTIGA® for the entire 24 week period. Patients had radical prostatectomies following their neoadjuvant therapy. Fifty eight patients were enrolled and the eligibility criteria included either T3 disease, a Gleason score of ≥7, a prostate-specific antigen (PSA) level ≥20, or a PSA velocity >2 ng/mL/year. Post prostatectomy specimen analysis revealed that patients treated with the combination of LUPRON® plus ZYTIGA® for the entire 24 week period has a complete pathologic response (pCR) or near complete pCR (≤ 5mm residual tumor) rate amounting to 34%. This benefit was seen without significant systemic toxicities. The authors concluded that neoadjuvant androgen deprivation therapy may significantly improve outcomes in high risk patients with localized disease and will need to be studied further. Taplin ME, Montgomery RB, Logothetis C, et al. J Clin Oncol 30, 2012 (suppl; abstr 4521)
Effect of MDV3100, an androgen receptor signaling inhibitor (ARSI), on overall survival in patients with prostate cancer post docetaxel Results from the phase III AFFIRM study
SUMMARY: MDV3100 is an androgen receptor antagonist with a significantly higher binding affinity for the androgen receptor (AR) compared to the antiandrogen bicalutamide and there by competitively inhibits the binding of androgens to the androgen receptor. Majority of the patients with advanced prostate cancer become refractory to hormone therapy because of increased production of androgen receptors by the tumors as well as mutated androgen receptors. The superiority of this novel agent, MDV3100, is based on the fact that the expression of androgen dependent genes are downregulated with MDV 3100 leading to cell death or apoptosis, whereas with bicalutamide the expression of these genes are upregulated. Further MDV3100 continues to antagonize mutated androgen receptors on the prostate tumor cells in contrast to bicalutamide which behaves as an agonist. It is thus an androgen receptor signaling inhibitor (ARSI). The AFFIRM clinical trial is a randomized, multinational phase III study in which patients who had received prior docetaxel-based chemotherapy regimens were randomized 2:1 to receive either MDV3100, 160 mg/day or placebo. Patients treated with MDV3100 had a median survival of 18.4 months, compared with 13.6 months for men treated with placebo, with a median OS advantage of 4.8 months and a reduction in the risk of death by 37%. Scher HI, Fizazi K, Saad F, et al. J Clin Oncol 30, 2012 (suppl 5; abstr LBA1)