- Email: [email protected]
TEN-YEAR TREATMENT OUTCOMES OF SALVAGE CRYOTHERAPY FOR LOCALLY RECURRENT PROSTATE CANCER
Vol. 179, No. 4, Supplement, Monday, May 19, 2008
(91% vs. 78%, p=0.004), and CSS (94% vs. 87%, p=0.02). Overall survival was similar in both groups (75% vs. 69%, p=0.12). Adjuvant RT tended to improve 10-year BPFS (38% vs 20%, p=0.06) and LRFS (96% vs. 78%, p=0.002), but did not impact SPFS (77% vs. 79%, p=0.60), CSS (86% vs. 88%, p=0.64), or OS (74% vs. 68%, p=0.17). CONCLUSIONS: Adjuvant ADT was associated with improved LRFS, SPFS, and CSS for pT3b prostate cancers, but did not impact OS, while adjuvant RT only improved BPFS and LRFS. Thus, while adjuvant ADT provides durable local and systemic control, adjuvant RT PD\QRWWREHDVEHQH¿FLDOIRUS7ESURVWDWHFDQFHU*LYHQWKHODFNRI improvement in OS noted here, continued investigations are needed to identify the cohort of pT3b patients at highest risk for cancer progression DQGWKHUHIRUHPRVWOLNHO\WREHQH¿WIURP$'7JLYHQWKHHPHUJLQJWR[LFLW\ data associated with long-term hormone therapy. Source of Funding: None
723 TEN-YEAR TREATMENT OUTCOMES OF SALVAGE CRYOTHERAPY FOR LOCALLY RECURRENT PROSTATE CANCER Omar Hamoui*, Lucas Wiegand, Louis L Pisters, Julie Bossier, Mike Hernandez, Philippe E Spiess. Tampa, FL, and Houston, TX. INTRODUCTION AND OBJECTIVE: To determine the longterm treatment outcomes of salvage cryotherapy for locally recurrent prostate cancer following primary radiotherapy. METHODS: A retrospective chart review was conducted of 110 patients treated with salvage cryotherapy for locally recurrent prostate cancer at the University of Texas M. D. Anderson Cancer Center. The median follow-up of patients following salvage cryotherapy was 7.9 \HDUV7KHSULPDU\HQGSRLQWRIWKLVVWXG\ZDVELRFKHPLFDOIDLOXUHGH¿QHG HLWKHUDVDVHUXP36$!QJPO GH¿QLWLRQ RU> 2 ng/ml above the SRVWFU\RWKHUDS\QDGLU36$ GH¿QLWLRQ RESULTS: Following salvage cryotherapy, 78 patients (71.6%) GHYHORSHGELRFKHPLFDOIDLOXUHXVLQJGH¿QLWLRQDQG XVLQJ GH¿QLWLRQ7KH\HDUGLVHDVHVSHFL¿FVXUYLYDORISDWLHQWVGHYHORSLQJ ELRFKHPLFDOIDLOXUHDFFRUGLQJWRGH¿QLWLRQDQGZDVDQG respectively. Common complications of salvage cryotherapy included mild/moderate urinary incontinence (39%), severe urinary incontinence (41%), and urinary retention (34%). The prognostic importance of a WZRIUHH]HWKDZF\FOHZDVIXUWKHUVXSSRUWHGZLWKRXUORQJWHUPUHVXOWV however this was at the expense of a slightly higher complication rate. CONCLUSIONS: Our long-term results further support the clinical utility of salvage cryotherapy for locally recurrent prostate cancer following primary radiotherapy. Salvage cryotherapy is curative in approximately one-third of patients at 10-year follow-up. Source of Funding: None
724 PHASE 2a TRIAL OF 177LUTETIUM RADIOLABELED ANTIPROSTATE-SPECIFIC MEMBRANE ANTIGEN (PSMA) MONOCLONAL ANTIBODY J591 (177Lu-J591) IN PATIENTS (PTS) WITH METASTATIC ANDROGEN-INDEPENDENT PROSTATE CANCER (AIPC) Neil H Bander*, David M Nanus, Scott Tagawa, Shankar Vallabhajosula, Stanley Goldsmith, Matthew I Milowsky, Michael Morris. New York, NY. INTRODUCTION AND OBJECTIVE: A phase 1 trial of 177Lu-J591 in pts with metastatic (met) AIPC demonstrated acceptable toxicity, excellent targeting of met sites and biologic activity. Our aim is to further study the activity and toxicity of 177Lu-J591 at the maximum tolerated dose. METHODS: Two successive cohorts of pts with progressive PHW$,3&UHFHLYHRQHGRVHRI/X- &RKRUW P&LP SWV Cohort 2: (70mCi/m2), 17 pts. The 1° endpoint is PSA and/or measurable GLVHDVHUHVSRQVHDWZHHNV HQGSRLQWLVWR[LFLW\$/X- LPDJLQJVWXG\LVGRQHWRFRQ¿UPWXPRUWDUJHWLQJ RESULTS: 30 of 32 planned pts have been treated to date, 15 in each cohort. All patients had extensive disease burdens, failed multiple forms of hormonal therapy and 18 (60%) pts had failed docetaxel chemotherapy. Responses are shown in the table below. Based on
THE JOURNAL OF UROLOGY®
253
WKH¿QGLQJIURPERWK7D[DQG6:2* WKDWD36$GHFOLQHRI UHSUHVHQWHGWKHEHVWVXUYLYDOVXUURJDWHZHDOVRVFRUHGD36$ GHFOLQHRI Response (PSA) GHFOLQH GHFOLQH 10-29% decline* Stable Progression Too Early
&RKRUW Q 1 (7%) 2 (13%) 4 (26%) 1 12 0
&RKRUW Q 1 (7%) 8 (57%) 1 (7%) 2 5 1
* Patients with 10-29% PSA declines are also scored in stable or progressed categories based on their status at 12 weeks. Toxicity: 9 patients required 1-4 platelet tx (median 2) to support them through the WUDQVLHQWWKURPERF\WRSHQLD'HVSLWHWKURPERF\WRSHQLDQRVLJQL¿FDQW hemorrhagic complications occurred. Of 27 evaluable pts, 24 had return WRQPOSOWFRXQWV WKHUHPDLQLQJKDGSURJUHVVLYHGLVHDVHDQGPDUURZ involvement. 6 pts in cohort 2 required brief granulocyte growth factor support. No serious drug-related non-hematologic toxicity has occurred. Excellent targeting of known sites of PC metastases was seen in 29 of 30 (97%) pts. CONCLUSIONS: Single dose 177Lu-J591 was generally well tolerated, with reversible myelosuppression, and demonstrates anti-tumor activity in pts with met, progressive AIPC. A dose-response relationship was evident in both toxicity and activity. Given that the RSWLPDOWXPRUVL]HIRU/XLVPPLGHDOSDWLHQWVZRXOGKDYHPLFUR met disease. The current experience supports extending this treatment to high risk pts with rapid PSA progression prior to development of met GLVHDVH UDQGRPL]HGSKDVHEWULDOVDUHSODQQHG Source of Funding: Dept of Defense, Cancer Research ,QVWLWXWH'DYLG+.RFK)RXQGDWLRQ%=/%LRORJLFV,QF
725 IS SAMARIUM-153- ETHYLENE-DIAMINO-TETRAMETHYLENEPHOSPHONATE (EDTMP) BONE UPTAKE INFLUENCED BY BIPHOSPHONATES? Matthias Waldert*, Mesut Remzi, Christian Kratuik, Helmut Sinzinger, Julian Mauermann, Michael Marberger. Vienna, Austria. INTRODUCTION AND OBJECTIVE: Bone is the most frequent site of metastatic spread in patients with prostate cancer causing severe bone pain in over 80% of patients. Currently administration of biphosphonates, external beam irradiation or administration of bone-seeking therapeutic radiopharmacon such as samarium-153ethylene-diamino-tetramethylene- phosphonate (EDTMP) are given in this clinical setting. Because biphophonates and Sm- 153 EDTMP are related compounds that concentrate in bone it was determined whether previous biphosphonate administration blocks subsequent uptake of of Sm- 153 EDTMP and therefore affects therapy outcome. METHODS: In this prospective study the bone uptake of Sm- 153 EDTMP in 40 patients with prostate cancer and multiple painful secondary bone lesions and no prior biphosphonate therapy was assessed. Sm- 153 EDTMP was repeated after three months in WKH SUHVHQFH RIELSKRVSKRQDWHV ]ROHGURQLF DFLG DGPLQLVWHUHG HYHU\ four weeks, first administration one week after Sm- 153 EDTMP administration, last administration 1 to 4 days before Sm- 153 EDTMP administration). All other treatment remained unchanged throughout the observation period. The retained activity in bone was calculated using whole body scintigraphy (acquisition 15cm/min) performed immediately after tracer application and after 6 hours. RESULTS: Mean patient age of the 40 patients was 69 +/4.8 years (range 57-77 years). Mean PSA level at study entry was 140 +/- 85 ng/mL (12- 2323). 5 patients had 3-5 bone lesions (12.5 %), 9 6-10 lesions (22.5%) and 26 more than 10 lesions (65%). None of them had soft tissue metastases. Bone uptake of Sm- 153 EDTMP ranged from 36.3%- 75.3% (mean 55.1 +/- 10.9%) before biphosphonate administration and 35.6%- 73.3% (mean 55.2 +/- 10.4%) after ELSKRVSKRQDWHDGPLQLVWUDWLRQ1RVLJQL¿FDQWLQWUDLQGLYLGXDOGLIIHUHQFH with or without biphosphonate treatment (p = 0.97) or stunning was REVHUYHG 3DLQ UHOLHI RQVHW DQG GXUDWLRQ RI HIIHFW DV ZHOO DV ÀDUH phenomenon and its duration were comparable.
(91% vs. 78%, p=0.004), and CSS (94% vs. 87%, p=0.02). Overall survival was similar in both groups (75% vs. 69%, p=0.12). Adjuvant RT tended to improve 10-year BPFS (38% vs 20%, p=0.06) and LRFS (96% vs. 78%, p=0.002), but did not impact SPFS (77% vs. 79%, p=0.60), CSS (86% vs. 88%, p=0.64), or OS (74% vs. 68%, p=0.17). CONCLUSIONS: Adjuvant ADT was associated with improved LRFS, SPFS, and CSS for pT3b prostate cancers, but did not impact OS, while adjuvant RT only improved BPFS and LRFS. Thus, while adjuvant ADT provides durable local and systemic control, adjuvant RT PD\QRWWREHDVEHQH¿FLDOIRUS7ESURVWDWHFDQFHU*LYHQWKHODFNRI improvement in OS noted here, continued investigations are needed to identify the cohort of pT3b patients at highest risk for cancer progression DQGWKHUHIRUHPRVWOLNHO\WREHQH¿WIURP$'7JLYHQWKHHPHUJLQJWR[LFLW\ data associated with long-term hormone therapy. Source of Funding: None
723 TEN-YEAR TREATMENT OUTCOMES OF SALVAGE CRYOTHERAPY FOR LOCALLY RECURRENT PROSTATE CANCER Omar Hamoui*, Lucas Wiegand, Louis L Pisters, Julie Bossier, Mike Hernandez, Philippe E Spiess. Tampa, FL, and Houston, TX. INTRODUCTION AND OBJECTIVE: To determine the longterm treatment outcomes of salvage cryotherapy for locally recurrent prostate cancer following primary radiotherapy. METHODS: A retrospective chart review was conducted of 110 patients treated with salvage cryotherapy for locally recurrent prostate cancer at the University of Texas M. D. Anderson Cancer Center. The median follow-up of patients following salvage cryotherapy was 7.9 \HDUV7KHSULPDU\HQGSRLQWRIWKLVVWXG\ZDVELRFKHPLFDOIDLOXUHGH¿QHG HLWKHUDVDVHUXP36$!QJPO GH¿QLWLRQ RU> 2 ng/ml above the SRVWFU\RWKHUDS\QDGLU36$ GH¿QLWLRQ RESULTS: Following salvage cryotherapy, 78 patients (71.6%) GHYHORSHGELRFKHPLFDOIDLOXUHXVLQJGH¿QLWLRQDQG XVLQJ GH¿QLWLRQ7KH\HDUGLVHDVHVSHFL¿FVXUYLYDORISDWLHQWVGHYHORSLQJ ELRFKHPLFDOIDLOXUHDFFRUGLQJWRGH¿QLWLRQDQGZDVDQG respectively. Common complications of salvage cryotherapy included mild/moderate urinary incontinence (39%), severe urinary incontinence (41%), and urinary retention (34%). The prognostic importance of a WZRIUHH]HWKDZF\FOHZDVIXUWKHUVXSSRUWHGZLWKRXUORQJWHUPUHVXOWV however this was at the expense of a slightly higher complication rate. CONCLUSIONS: Our long-term results further support the clinical utility of salvage cryotherapy for locally recurrent prostate cancer following primary radiotherapy. Salvage cryotherapy is curative in approximately one-third of patients at 10-year follow-up. Source of Funding: None
724 PHASE 2a TRIAL OF 177LUTETIUM RADIOLABELED ANTIPROSTATE-SPECIFIC MEMBRANE ANTIGEN (PSMA) MONOCLONAL ANTIBODY J591 (177Lu-J591) IN PATIENTS (PTS) WITH METASTATIC ANDROGEN-INDEPENDENT PROSTATE CANCER (AIPC) Neil H Bander*, David M Nanus, Scott Tagawa, Shankar Vallabhajosula, Stanley Goldsmith, Matthew I Milowsky, Michael Morris. New York, NY. INTRODUCTION AND OBJECTIVE: A phase 1 trial of 177Lu-J591 in pts with metastatic (met) AIPC demonstrated acceptable toxicity, excellent targeting of met sites and biologic activity. Our aim is to further study the activity and toxicity of 177Lu-J591 at the maximum tolerated dose. METHODS: Two successive cohorts of pts with progressive PHW$,3&UHFHLYHRQHGRVHRI/X- &RKRUW P&LP SWV Cohort 2: (70mCi/m2), 17 pts. The 1° endpoint is PSA and/or measurable GLVHDVHUHVSRQVHDWZHHNV HQGSRLQWLVWR[LFLW\$/X- LPDJLQJVWXG\LVGRQHWRFRQ¿UPWXPRUWDUJHWLQJ RESULTS: 30 of 32 planned pts have been treated to date, 15 in each cohort. All patients had extensive disease burdens, failed multiple forms of hormonal therapy and 18 (60%) pts had failed docetaxel chemotherapy. Responses are shown in the table below. Based on
THE JOURNAL OF UROLOGY®
253
WKH¿QGLQJIURPERWK7D[DQG6:2* WKDWD36$GHFOLQHRI UHSUHVHQWHGWKHEHVWVXUYLYDOVXUURJDWHZHDOVRVFRUHGD36$ GHFOLQHRI Response (PSA) GHFOLQH GHFOLQH 10-29% decline* Stable Progression Too Early
&RKRUW Q 1 (7%) 2 (13%) 4 (26%) 1 12 0
&RKRUW Q 1 (7%) 8 (57%) 1 (7%) 2 5 1
* Patients with 10-29% PSA declines are also scored in stable or progressed categories based on their status at 12 weeks. Toxicity: 9 patients required 1-4 platelet tx (median 2) to support them through the WUDQVLHQWWKURPERF\WRSHQLD'HVSLWHWKURPERF\WRSHQLDQRVLJQL¿FDQW hemorrhagic complications occurred. Of 27 evaluable pts, 24 had return WRQPOSOWFRXQWV WKHUHPDLQLQJKDGSURJUHVVLYHGLVHDVHDQGPDUURZ involvement. 6 pts in cohort 2 required brief granulocyte growth factor support. No serious drug-related non-hematologic toxicity has occurred. Excellent targeting of known sites of PC metastases was seen in 29 of 30 (97%) pts. CONCLUSIONS: Single dose 177Lu-J591 was generally well tolerated, with reversible myelosuppression, and demonstrates anti-tumor activity in pts with met, progressive AIPC. A dose-response relationship was evident in both toxicity and activity. Given that the RSWLPDOWXPRUVL]HIRU/XLVPPLGHDOSDWLHQWVZRXOGKDYHPLFUR met disease. The current experience supports extending this treatment to high risk pts with rapid PSA progression prior to development of met GLVHDVH UDQGRPL]HGSKDVHEWULDOVDUHSODQQHG Source of Funding: Dept of Defense, Cancer Research ,QVWLWXWH'DYLG+.RFK)RXQGDWLRQ%=/%LRORJLFV,QF
725 IS SAMARIUM-153- ETHYLENE-DIAMINO-TETRAMETHYLENEPHOSPHONATE (EDTMP) BONE UPTAKE INFLUENCED BY BIPHOSPHONATES? Matthias Waldert*, Mesut Remzi, Christian Kratuik, Helmut Sinzinger, Julian Mauermann, Michael Marberger. Vienna, Austria. INTRODUCTION AND OBJECTIVE: Bone is the most frequent site of metastatic spread in patients with prostate cancer causing severe bone pain in over 80% of patients. Currently administration of biphosphonates, external beam irradiation or administration of bone-seeking therapeutic radiopharmacon such as samarium-153ethylene-diamino-tetramethylene- phosphonate (EDTMP) are given in this clinical setting. Because biphophonates and Sm- 153 EDTMP are related compounds that concentrate in bone it was determined whether previous biphosphonate administration blocks subsequent uptake of of Sm- 153 EDTMP and therefore affects therapy outcome. METHODS: In this prospective study the bone uptake of Sm- 153 EDTMP in 40 patients with prostate cancer and multiple painful secondary bone lesions and no prior biphosphonate therapy was assessed. Sm- 153 EDTMP was repeated after three months in WKH SUHVHQFH RIELSKRVSKRQDWHV ]ROHGURQLF DFLG DGPLQLVWHUHG HYHU\ four weeks, first administration one week after Sm- 153 EDTMP administration, last administration 1 to 4 days before Sm- 153 EDTMP administration). All other treatment remained unchanged throughout the observation period. The retained activity in bone was calculated using whole body scintigraphy (acquisition 15cm/min) performed immediately after tracer application and after 6 hours. RESULTS: Mean patient age of the 40 patients was 69 +/4.8 years (range 57-77 years). Mean PSA level at study entry was 140 +/- 85 ng/mL (12- 2323). 5 patients had 3-5 bone lesions (12.5 %), 9 6-10 lesions (22.5%) and 26 more than 10 lesions (65%). None of them had soft tissue metastases. Bone uptake of Sm- 153 EDTMP ranged from 36.3%- 75.3% (mean 55.1 +/- 10.9%) before biphosphonate administration and 35.6%- 73.3% (mean 55.2 +/- 10.4%) after ELSKRVSKRQDWHDGPLQLVWUDWLRQ1RVLJQL¿FDQWLQWUDLQGLYLGXDOGLIIHUHQFH with or without biphosphonate treatment (p = 0.97) or stunning was REVHUYHG 3DLQ UHOLHI RQVHW DQG GXUDWLRQ RI HIIHFW DV ZHOO DV ÀDUH phenomenon and its duration were comparable.