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Clarke, N.W.; Ali, A.; Ingleby, F.C.; Hoyle, A.; Amos, C.L.; Attard, G.; Brawley, C.D.; Calvert, J.; Chowdhury, S.; Cook, A.; Cross, W.; Dearnaley, D.P.; Douis, H.; Gilbert, D.; Gillessen, S.; Jones, R.J.; Langley, R.E.; MacNair, A.; Malik, Z.; Mason, M.D.; Matheson, D.; Millman, R.; Parker, C.C.; Ritchie, A.W.S.; Rush, H.; Russell, J.M.; Brown, J.; Beesley, S.; Birtle, A.; Capaldi, L.; Gale, J.; Gibbs, S.; Lydon, A.; Nikapota, A.; Omlin, A.; O'Sullivan, J.M.; Parikh, O.; Protheroe, A.; Rudman, S.; Srihari, N.N.; Simms, M.; Tanguay, J.S.; Tolan, S.; Wagstaff, J.; Wallace, J.; Wylie, J.; Zarkar, A.; Sydes, M.R.; Parmar, M.K.B.; James, N.D.
Annals of oncology, 12/2019, Letnik: 30, Številka: 12Journal Article
STAMPEDE has previously reported that the use of upfront docetaxel improved overall survival (OS) for metastatic hormone naïve prostate cancer patients starting long-term androgen deprivation therapy. We report on long-term outcomes stratified by metastatic burden for M1 patients. We randomly allocated patients in 2 : 1 ratio to standard-of-care (SOC; control group) or SOC + docetaxel. Metastatic disease burden was categorised using retrospectively-collected baseline staging scans where available. Analysis used Cox regression models, adjusted for stratification factors, with emphasis on restricted mean survival time where hazards were non-proportional. Between 05 October 2005 and 31 March 2013, 1086 M1 patients were randomised to receive SOC (n = 724) or SOC + docetaxel (n = 362). Metastatic burden was assessable for 830/1086 (76%) patients; 362 (44%) had low and 468 (56%) high metastatic burden. Median follow-up was 78.2 months. There were 494 deaths on SOC (41% more than the previous report). There was good evidence of benefit of docetaxel over SOC on OS (HR = 0.81, 95% CI 0.69–0.95, P = 0.009) with no evidence of heterogeneity of docetaxel effect between metastatic burden sub-groups (interaction P = 0.827). Analysis of other outcomes found evidence of benefit for docetaxel over SOC in failure-free survival (HR = 0.66, 95% CI 0.57–0.76, P < 0.001) and progression-free survival (HR = 0.69, 95% CI 0.59–0.81, P < 0.001) with no evidence of heterogeneity of docetaxel effect between metastatic burden sub-groups (interaction P > 0.5 in each case). There was no evidence that docetaxel resulted in late toxicity compared with SOC: after 1 year, G3-5 toxicity was reported for 28% SOC and 27% docetaxel (in patients still on follow-up at 1 year without prior progression). The clinically significant benefit in survival for upfront docetaxel persists at longer follow-up, with no evidence that benefit differed by metastatic burden. We advocate that upfront docetaxel is considered for metastatic hormone naïve prostate cancer patients regardless of metastatic burden.
