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711 EFFECTS OF DENOSUMAB AND ZOLEDRONIC ACID ON PAIN INTERFERENCE WITH DAILY FUNCTIONING IN PATIENTS WITH CASTRATE-RESISTANT PROSTATE CANCER
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THE JOURNAL OF UROLOGY姞
Vol. 185, No. 4S, Supplement, Monday, May 16, 2011
events reported were grade 2. G3– 4 were mainly hematological toxicity. Frequency of AEs related to docetaxel did not seem to be modified. 82% of the patients had ⱖ30% PSA decline within 3 months of treatment whereas in historical data around 65% are responder with docetaxel as a single agent. PSA response was observed after 1 cycle of treatment in 43% of the patients. Time to biochemical relapse defined as an increase of 25% over nadir was 169 days. CONCLUSIONS: High antiproliferative daily dose of inecalcitol, a new VDR, agonist has been safely used in combination with docetaxel in CRPC patients. This combination treatment shows encouraging PSA response (⬎ 30% PSA response: 82%). A multicenter randomized double blind Phase 3 study is forecasted to confirm these results. Source of Funding: Hybrigenics
711 EFFECTS OF DENOSUMAB AND ZOLEDRONIC ACID ON PAIN INTERFERENCE WITH DAILY FUNCTIONING IN PATIENTS WITH CASTRATE-RESISTANT PROSTATE CANCER Donald Patrick*, Seattle, WA; Charles Cleeland, Houston, TX; Lesley Fallowfield, Brighton, United Kingdom; Matthew R. Smith, Boston, MA; John Trachtenberg, Toronto, Canada; Petyo Chilingirov, Stara Zagora, Bulgaria; Maurice-Stephan Michel, Mannheim, Germany; Stephane Oudard, Paris, France; Amy Feng, Carsten Goessl, Karen Chung, Thousand Oaks, CA INTRODUCTION AND OBJECTIVES: In a recently completed randomized phase 3 trial in men with castrate-resistant prostate cancer (CRPC), denosumab, a fully human monoclonal antibody to RANKL, was superior to zoledronic acid (ZA) for prevention of skeletal complications of bone metastases. Of patients (pts) with no/mild baseline pain ⱕ 4, fewer pts in the denosumab group had pain worsening over the study. Here we report between-treatment differences in pain interference with daily functioning. METHODS: Eligible pts with CRPC and ⱖ 1 site of bone metastasis received either subcutaneous (SC) denosumab 120 mg and intravenous (IV) placebo (n⫽950) or IV ZA 4 mg and SC placebo (n⫽951) every 4 weeks. The Brief Pain Inventory (BPI) assessed pain interference with daily functioning (pain interference with activity domain [general activity, walking, work] and with affect domain [mood, enjoyment of life, relations with others]) on a scale of 0 (no) to 10 (complete) interference. Pts completed the BPI at baseline, day 8, and before each monthly visit through the end of study. Analyses included all randomized pts and were performed through week 73, when ⱖ 50% of pts had dropped out due to death, disease progression, or consent withdrawal. RESULTS: Time to worsening of pain interference (ⱖ 2 point increase) was longer with denosumab compared with ZA (N⫽1699; median 252 days denosumab vs 228 days ZA; P⫽0.19). Among pts with baseline worst pain score ⱕ 4, time to worsening with affect (ⱖ 2 point increase) was significantly longer with denosumab (N⫽991; median 252 days denosumab vs 202 days ZA; P⫽0.02) and denosumab also tended to prolong the time to worsening with activity (ⱖ 2 point increase; N⫽993; median 203 days denosumab vs 192 days ZA; P⫽0.08). From week 5 to 73, a greater proportion of denosumab patients experienced an improvement of general activity over time (ⱖ 2-point decrease) compared with ZA (Figure). CONCLUSIONS: Denosumab delayed worsening of pain interference with trends extending to activity and affect domains for patients with baseline worst pain score ⱕ 4. Denosumab also produced a consistent difference in the proportion of pts reporting decreased pain interference with general activity over the study period. There was a consistent incremental benefit in pain interference by denosumab.
Source of Funding: Amgen Inc
712 RISK OF DEVELOPMENT OF PROTEINURIA WITH ANDROGEN DEPRIVATION THERAPY FOR PROSTATE CANCER Reza Mehrazin*, Michael Aleman, Jamin Brahmbhatt, Anthony Patterson, Memphis, TN; Ithaar Derweesh, San Diago, CA; Christopher Ledbetter, Jim Wan, Robert Wake, Memphis, TN INTRODUCTION AND OBJECTIVES: Although risks of development of hypertension (HTN), diabetes mellitus (DM), and cardiovascular adverse effects have been published, there is a paucity of data describing the effect of Androgen deprivation therapy (ADT) on renal function and development of proteinuria. METHODS: We retrospectively reviewed patients who receivev ADT for CaP at a single center between 7/1987–1/2010. Men receiving only neoadjuvant ADT or with incomplete information were excluded. Variables included were: age at ADT initiation, race, pre-ADT PSA, length of followup, pre and post treatment GFR (MDRD), and presence of pre and postoperative HTN, DM, and proteinuria. Diagnoses of HTN, DM, renal failure, or renal insufficiency were based on a computerized diagnosis list and/or the presence of medical therapy for the disease. The data were then analyzed by chi-square test and by logistic regression analysis. RESULTS: A total of 765 men were included in the cohort. Mean age at CaP diagnosis and ADT initiation were 69.8 (36.9 – 89.1) and 71.2 years (47.4 –95.1), respectively. 305 (39.9%) patients were Caucasian, while 460 (60.1%) were African-American. Mean pre-ADT PSA was 114 ng/ml (median 16.4; 0.42– 6031). During a mean followup of 87.7 months, 59.8%, 17.9%, 17.1%, and 7.3% developed HTN, DM, proteinuria, and chronic renal failure, respectively. Upon multivariable analysis, length of follow-up (p⬍0.0001) and BMI⬎30 (p⫽0.0063) were the only factors associated with development of de novo HTN and DM respectively. Comparably, age (p⫽0.0024) and African American race (p⫽0.0008) were found to be significant the variables associated with the development of proteinuria. On multivariable analyses, no analyzed variables were found to be associated with decline in GFR in the cohort; interestingly, a small overall mean increase in GFR of 0.30 mL/min/ 1.73m2 was noted among the entire cohort after ADT treatment. CONCLUSIONS: In our experience, African American race and age were found to be risk factors for development of de novo proteinuria in patients who receive ADT for CaP. Overall patients in our cohort showed improvement of GFR based on the MDRD equation, but a
THE JOURNAL OF UROLOGY姞
Vol. 185, No. 4S, Supplement, Monday, May 16, 2011
events reported were grade 2. G3– 4 were mainly hematological toxicity. Frequency of AEs related to docetaxel did not seem to be modified. 82% of the patients had ⱖ30% PSA decline within 3 months of treatment whereas in historical data around 65% are responder with docetaxel as a single agent. PSA response was observed after 1 cycle of treatment in 43% of the patients. Time to biochemical relapse defined as an increase of 25% over nadir was 169 days. CONCLUSIONS: High antiproliferative daily dose of inecalcitol, a new VDR, agonist has been safely used in combination with docetaxel in CRPC patients. This combination treatment shows encouraging PSA response (⬎ 30% PSA response: 82%). A multicenter randomized double blind Phase 3 study is forecasted to confirm these results. Source of Funding: Hybrigenics
711 EFFECTS OF DENOSUMAB AND ZOLEDRONIC ACID ON PAIN INTERFERENCE WITH DAILY FUNCTIONING IN PATIENTS WITH CASTRATE-RESISTANT PROSTATE CANCER Donald Patrick*, Seattle, WA; Charles Cleeland, Houston, TX; Lesley Fallowfield, Brighton, United Kingdom; Matthew R. Smith, Boston, MA; John Trachtenberg, Toronto, Canada; Petyo Chilingirov, Stara Zagora, Bulgaria; Maurice-Stephan Michel, Mannheim, Germany; Stephane Oudard, Paris, France; Amy Feng, Carsten Goessl, Karen Chung, Thousand Oaks, CA INTRODUCTION AND OBJECTIVES: In a recently completed randomized phase 3 trial in men with castrate-resistant prostate cancer (CRPC), denosumab, a fully human monoclonal antibody to RANKL, was superior to zoledronic acid (ZA) for prevention of skeletal complications of bone metastases. Of patients (pts) with no/mild baseline pain ⱕ 4, fewer pts in the denosumab group had pain worsening over the study. Here we report between-treatment differences in pain interference with daily functioning. METHODS: Eligible pts with CRPC and ⱖ 1 site of bone metastasis received either subcutaneous (SC) denosumab 120 mg and intravenous (IV) placebo (n⫽950) or IV ZA 4 mg and SC placebo (n⫽951) every 4 weeks. The Brief Pain Inventory (BPI) assessed pain interference with daily functioning (pain interference with activity domain [general activity, walking, work] and with affect domain [mood, enjoyment of life, relations with others]) on a scale of 0 (no) to 10 (complete) interference. Pts completed the BPI at baseline, day 8, and before each monthly visit through the end of study. Analyses included all randomized pts and were performed through week 73, when ⱖ 50% of pts had dropped out due to death, disease progression, or consent withdrawal. RESULTS: Time to worsening of pain interference (ⱖ 2 point increase) was longer with denosumab compared with ZA (N⫽1699; median 252 days denosumab vs 228 days ZA; P⫽0.19). Among pts with baseline worst pain score ⱕ 4, time to worsening with affect (ⱖ 2 point increase) was significantly longer with denosumab (N⫽991; median 252 days denosumab vs 202 days ZA; P⫽0.02) and denosumab also tended to prolong the time to worsening with activity (ⱖ 2 point increase; N⫽993; median 203 days denosumab vs 192 days ZA; P⫽0.08). From week 5 to 73, a greater proportion of denosumab patients experienced an improvement of general activity over time (ⱖ 2-point decrease) compared with ZA (Figure). CONCLUSIONS: Denosumab delayed worsening of pain interference with trends extending to activity and affect domains for patients with baseline worst pain score ⱕ 4. Denosumab also produced a consistent difference in the proportion of pts reporting decreased pain interference with general activity over the study period. There was a consistent incremental benefit in pain interference by denosumab.
Source of Funding: Amgen Inc
712 RISK OF DEVELOPMENT OF PROTEINURIA WITH ANDROGEN DEPRIVATION THERAPY FOR PROSTATE CANCER Reza Mehrazin*, Michael Aleman, Jamin Brahmbhatt, Anthony Patterson, Memphis, TN; Ithaar Derweesh, San Diago, CA; Christopher Ledbetter, Jim Wan, Robert Wake, Memphis, TN INTRODUCTION AND OBJECTIVES: Although risks of development of hypertension (HTN), diabetes mellitus (DM), and cardiovascular adverse effects have been published, there is a paucity of data describing the effect of Androgen deprivation therapy (ADT) on renal function and development of proteinuria. METHODS: We retrospectively reviewed patients who receivev ADT for CaP at a single center between 7/1987–1/2010. Men receiving only neoadjuvant ADT or with incomplete information were excluded. Variables included were: age at ADT initiation, race, pre-ADT PSA, length of followup, pre and post treatment GFR (MDRD), and presence of pre and postoperative HTN, DM, and proteinuria. Diagnoses of HTN, DM, renal failure, or renal insufficiency were based on a computerized diagnosis list and/or the presence of medical therapy for the disease. The data were then analyzed by chi-square test and by logistic regression analysis. RESULTS: A total of 765 men were included in the cohort. Mean age at CaP diagnosis and ADT initiation were 69.8 (36.9 – 89.1) and 71.2 years (47.4 –95.1), respectively. 305 (39.9%) patients were Caucasian, while 460 (60.1%) were African-American. Mean pre-ADT PSA was 114 ng/ml (median 16.4; 0.42– 6031). During a mean followup of 87.7 months, 59.8%, 17.9%, 17.1%, and 7.3% developed HTN, DM, proteinuria, and chronic renal failure, respectively. Upon multivariable analysis, length of follow-up (p⬍0.0001) and BMI⬎30 (p⫽0.0063) were the only factors associated with development of de novo HTN and DM respectively. Comparably, age (p⫽0.0024) and African American race (p⫽0.0008) were found to be significant the variables associated with the development of proteinuria. On multivariable analyses, no analyzed variables were found to be associated with decline in GFR in the cohort; interestingly, a small overall mean increase in GFR of 0.30 mL/min/ 1.73m2 was noted among the entire cohort after ADT treatment. CONCLUSIONS: In our experience, African American race and age were found to be risk factors for development of de novo proteinuria in patients who receive ADT for CaP. Overall patients in our cohort showed improvement of GFR based on the MDRD equation, but a