Konference: 2009 34st Congress ESMO a 15th Congress ECCO - účast ČR
Kategorie: Genitourinární nádory
Téma: Proffered paper session: Genitourinary malignancies - Prostate cancer
Číslo abstraktu: O-7003
Autoři: C. Parker; P. Hoskin; S. Pascoe; A. Chodack; J.M. O'Sullivan; J.R. Germá; A. Lokna
Background: Alpharadin® (radium-223) is a bone-seeking alpha
emitting radioisotope now in phase III development for the
treatment of CRPC. In contrast to older pain palliating
radioisotopes used in CRPC, Alpharadin®is a new generation
α-emitter, and the very short range, high-energy α-radiation may
provide efficacy while sparing the bone marrow. The main objective
of the study was to compare the prostate specific antigen (PSA)
response rate of three different repeat doses of Alpharadin® in
patients with CRPC and bone metastases. Secondary objectives
included study of the effect of dose on changes in PSA,
bone-specific alkaline phosphatase (b-ALP) and toxicity.
Materials and Methods: Patients had CRPC with bone metastases and without visceral disease, a castrate testosterone, Eastern Cooperative Oncology Group (ECOG) performance status 0–2, and PSA progression according to the PSA Working Group criteria. They were randomised to one of three Alpharadin® dose groups: 25, 50 or 80 kBq/kg, given once every 6 weeks for 3 cycles. The planned sample size was 117. The main outcome was PSA response (defined as a 50% decline confirmed ≥19 days later), with censoring at the time of new CRPC treatment or anti-androgen withdrawal. The study was done in 21 centres from 2006–8.
Results: 121 eligible patients, median age 70 years, median baseline PSA 127.6 ng/ml, were analyzed by intention-to treat. Thirty-seven (31%) had received prior chemotherapy. 107 (88%) received all 3 Alpharadin® treatments over 12 weeks. Confirmed PSA response was seen in 0%, 6% and 13% in the 25, 50 and 80 kBq/kg groups, respectively (p = 0.0297 test for trend). The median change in PSA at week 16 was 71%, 42% and 24%, respectively (p = 0.050), and in b-ALP was -34%, -58% and -61% (p < 0.0001). Alpharadin® was well tolerated. No patients stopped study treatment for toxicity. The most common adverse events were G-I and musculo-skeletal, with no evidence of a dose-effect. Grade 3 or 4 neutropenia was not seen. Grade 3 or 4 thrombocytopenia occurred in 2 patients, one from each of the 2 lower dose groups.
Conclusions: The study met the primary endpoint, showing a dose response for % PSA responders. In addition to the biochemical evidence of efficacy, Alpharadin® had a highly favourable toxicity profile. The results support the dose schedule used in the ongoing ALSYMPCA phase III trial, 50 kBq/kg every 4 weeks for 6 cycles.
Trial sponsor: Algeta
Publikováno v: European Journal of Cancer Supplements, Vol 7 No 2, September 2009, Page 406
Materials and Methods: Patients had CRPC with bone metastases and without visceral disease, a castrate testosterone, Eastern Cooperative Oncology Group (ECOG) performance status 0–2, and PSA progression according to the PSA Working Group criteria. They were randomised to one of three Alpharadin® dose groups: 25, 50 or 80 kBq/kg, given once every 6 weeks for 3 cycles. The planned sample size was 117. The main outcome was PSA response (defined as a 50% decline confirmed ≥19 days later), with censoring at the time of new CRPC treatment or anti-androgen withdrawal. The study was done in 21 centres from 2006–8.
Results: 121 eligible patients, median age 70 years, median baseline PSA 127.6 ng/ml, were analyzed by intention-to treat. Thirty-seven (31%) had received prior chemotherapy. 107 (88%) received all 3 Alpharadin® treatments over 12 weeks. Confirmed PSA response was seen in 0%, 6% and 13% in the 25, 50 and 80 kBq/kg groups, respectively (p = 0.0297 test for trend). The median change in PSA at week 16 was 71%, 42% and 24%, respectively (p = 0.050), and in b-ALP was -34%, -58% and -61% (p < 0.0001). Alpharadin® was well tolerated. No patients stopped study treatment for toxicity. The most common adverse events were G-I and musculo-skeletal, with no evidence of a dose-effect. Grade 3 or 4 neutropenia was not seen. Grade 3 or 4 thrombocytopenia occurred in 2 patients, one from each of the 2 lower dose groups.
Conclusions: The study met the primary endpoint, showing a dose response for % PSA responders. In addition to the biochemical evidence of efficacy, Alpharadin® had a highly favourable toxicity profile. The results support the dose schedule used in the ongoing ALSYMPCA phase III trial, 50 kBq/kg every 4 weeks for 6 cycles.
Trial sponsor: Algeta
Publikováno v: European Journal of Cancer Supplements, Vol 7 No 2, September 2009, Page 406
Datum přednesení příspěvku: 21. 9. 2009
