期刊论文详细信息
BMC Health Services Research
Drug costs in the management of metastatic castration-resistant prostate cancer in Canada
Armen G Aprikian4  Fabio L Cury2  Marie Vanhuyse3  Daniela Dinea1  Alice Dragomir5 
[1] Faculty of Pharmacy, University of Montreal, CP 6128 Succursale Centre-Ville, Montreal, Quebec H3C 3 J7, Canada;Department of Oncology, Division of Radiation Oncology, McGill University, 1650 Cedar Avenue, Montreal, Quebec H3G 1A4, Canada;Department of Oncology, Division of Medical Oncology, McGill University, 1650 Cedar Avenue, Montreal, Quebec H3G 1A4, Canada;McGill University Health Center, 1650 Cedar Avenue, Montreal, Quebec H3G 1A4, Canada;Research Institute of McGill University Health Center, 2155 Guy St, Montreal, Quebec H3H 2R9, Canada
关键词: Cost of drugs for metastatic castration-resistant prostate cancer in Canada;    Markov model;    Cost of treatments;    Treatments for advanced prostate cancer;    Metastatic castration-resistant prostate cancer;   
Others  :  1130820
DOI  :  10.1186/1472-6963-14-252
 received in 2013-08-30, accepted in 2014-06-06,  发布年份 2014
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【 摘 要 】

Background

For Canadian men, prostate cancer (PCa) is the most common cancer and the 3rd leading cause of cancer mortality. Men dying of PCa do so after failing castration. The management of metastatic castration-resistant prostate cancer (mCRPC) is complex and the associated drug treatments are increasingly costly. The objective of this study was to estimate the cost of drug treatments over the mCRPC period, in the context of the latest evidence-based approaches.

Methods

Two Markov models with Monte-Carlo microsimulations were developed in order to simulate the management of the disease and to estimate the cost of drug treatments in mCRPC, as per Quebec’s public healthcare system. The models include recently approved additional lines of treatment after or before docetaxel (i.e. abiraterone and cabazitaxel). Drug exposure and survival were based on clinical trial results and clinical practice guidelines found in a literature review. All costs were assigned in 2013 Canadian dollars ($). Only direct drug costs were estimated.

Results

The mean cost of mCRPC drug treatments over an average period of 28.1 months was estimated at $48,428 per patient (95% Confidence Interval: $47,624 to $49,232). The mean cost increased to $104,071 (95% CI: $102,373 - $105,770) per patient when one includes abiraterone initiation prior to docetaxel therapy. Over the mCRPC period, luteinizing hormone-releasing hormone agonists (LHRHa) prescribed to maintain castrate testosterone levels accounted for 20.4% of the total medication cost, whereas denosumab prescribed to decrease bone-related events accounted for 30.5% of costs. When patients received cabazitaxel in sequence after abiraterone and docetaxel, the mCRPC medications cost per patient per month increased by 60.2%. The total cost of medications for the treatment of each annual Canadian cohort of 4,000 mCRPC patients was estimated at $ 193.6 million to $416.3 million.

Conclusions

Our study estimates the direct drug costs associated with mCRPC treatments in the Canadian healthcare system. Recently identified effective yet not approved therapies will become part of the spectrum of mCRPC treatments, and may potentially increase the cost.

【 授权许可】

   
2014 Dragomir et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Statistics Canada: Canadian Cancer Statistics 2012. Toronto, ON: Canadian Cancer Society; 2012.
  • [2]Huggins C, Hodges CV: Studies on prostatic cancer: I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. 1941. J Urol 2002, 168(1):9-12. Epub 2002/06/07
  • [3]Huggins C, Hodges CV: Studies on prostatic cancer. I. The effect of castration, of estrogen and androgen injection on serum phosphatases in metastatic carcinoma of the prostate. CA Cancer J Clin 1972, 22(4):232-240. Epub 1972/07/01
  • [4]de Jong IJ, Eaton A, Bladou F: LHRH agonists in prostate cancer: frequency of treatment, serum testosterone measurement and castrate level: consensus opinion from a roundtable discussion. Curr Med Res Opin 2007, 23(5):1077-1080. Epub 2007/05/24
  • [5]Labrie F: Medical castration with LHRH agonists: 25 years later with major benefits achieved on survival in prostate cancer. J Androl 2004, 25(3):305-313. Epub 2004/04/06
  • [6]Cook T, Sheridan WP: Development of GnRH antagonists for prostate cancer: new approaches to treatment. Oncologist 2000, 5(2):162-168. Epub 2000/05/05
  • [7]Moul JW: Prostate cancer: Making the switch from LHRH antagonist to LHRH agonist. Nat Rev Urol 2012, 9(3):125-126. Epub 2012/02/01
  • [8]Keizman D, Eisenberger MA: LHRH antagonists vs LHRH agonists: which is more beneficial in prostate cancer therapy? Oncology (Williston Park) 2009, 23(7):631-632. Epub 2009/07/25
  • [9]Crawford ED, Hou AH: The role of LHRH antagonists in the treatment of prostate cancer. Oncology (Williston Park) 2009, 23(7):626-630. Epub 2009/07/25
  • [10]Weston P, Persson BE: Re: Weckermann D, Harzmann R. Hormone therapy in prostate cancer: LHRH antagonists versus LHRH analogues. Eur Urol 2004;46:279–84. Eur Urol 2005, 47(3):422. author reply. Epub 2005/02/18
  • [11]Schroder F, Crawford ED, Axcrona K, Payne H, Keane TE: Androgen deprivation therapy: past, present and future. BJU Int 2012, 109(Suppl 6):1-12. Epub 2012/06/15
  • [12]Newling DW, Denis L, Vermeylen K: Orchiectomy versus goserelin and flutamide in the treatment of newly diagnosed metastatic prostate cancer. Analysis of the criteria of evaluation used in the European Organization for Research and Treatment of Cancer--Genitourinary Group Study 30853. Cancer 1993, 72(12 Suppl):3793-3798. Epub 1993/12/15
  • [13]Kirby M, Hirst C, Crawford ED: Characterising the castration-resistant prostate cancer population: a systematic review. Int J Clin Pract 2011, 65(11):1180-1192. Epub 2011/10/15
  • [14]Lee JL, Eun Kim J, Ahn JH, Lee DH, Lee J, Kim CS, Hyuk Hong J, Hong B, Song C, Ahn H: Role of androgen deprivation treatment in patients with castration-resistant prostate cancer, receiving docetaxel-based chemotherapy. Am J Clin Oncol 2011, 34(2):140-144. Epub 2010/08/06
  • [15]Morrissey C, Roudier MP, Dowell A, True LD, Ketchanji M, Welty C, Corey E, Lange PH, Higano CS, Vessella RL: Effects of androgen deprivation therapy and bisphosphonate treatment on bone in patients with metastatic castration resistant prostate cancer: results from the University of Washington rapid autopsy series. J Bone Miner Res 2012. Epub 2012/09/01
  • [16]Usami M, Akaza H, Arai Y, Hirano Y, Kagawa S, Kanetake H, Naito S, Sumiyoshi Y, Takimoto Y, Terai A, Yoshida H, Ohashi Y: Bicalutamide 80 mg combined with a luteinizing hormone-releasing hormone agonist (LHRH-A) versus LHRH-A monotherapy in advanced prostate cancer: findings from a phase III randomized, double-blind, multicenter trial in Japanese patients. Prostate Cancer Prostatic Dis 2007, 10(2):194-201. Epub 2007/01/03
  • [17]Manikandan R, Srirangam SJ, Pearson E, Brown SC, O'Reilly P, Collins GN: Diethylstilboestrol versus bicalutamide in hormone refractory prostate carcinoma: a prospective randomized trial. Urol Int 2005, 75(3):217-221. Epub 2005/10/11
  • [18]Small EJ, Halabi S, Dawson NA, Stadler WM, Rini BI, Picus J, Gable P, Torti FM, Kaplan E, Vogelzang NJ: Antiandrogen withdrawal alone or in combination with ketoconazole in androgen-independent prostate cancer patients: a phase III trial (CALGB 9583). J Clin Oncol 2004, 22(6):1025-1033. Epub 2004/03/17
  • [19]Paul R, Breul J: Antiandrogen withdrawal syndrome associated with prostate cancer therapies: incidence and clinical significance. Drug Saf 2000, 23(5):381-390. Epub 2000/11/21
  • [20]Ryan CJ, Smith MR, de Bono JS, Molina A, Logothetis CJ, de Souza P, Fizazi K, Mainwaring P, Piulats JM, Ng S, Carles J, Mulders PF, Basch E, Small EJ, Saad F, Schrijvers D, Van Poppel H, Mukherjee SD, Suttmann H, Gerritsen WR, Flaig TW, George DJ, Yu EY, Efstathiou E, Pantuck A, Winquist E, Higano CS, Taplin ME, Park Y, Kheoh T, et al.: Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med 2013, 368(2):138-148. Epub 2012/12/12
  • [21]Peters JL, Fairney A, Kyd P, Patel A, Rogers S, Webster JJ, Vale JA, Witherow RO: Bone loss associated with the use of LHRH agonists in prostate cancer. Prostate Cancer Prostatic Dis 2001, 4(3):161-166. Epub 2002/12/24
  • [22]Pockett RD, Castellano D, McEwan P, Oglesby A, Barber BL, Chung K: The hospital burden of disease associated with bone metastases and skeletal-related events in patients with breast cancer, lung cancer, or prostate cancer in Spain. Eur J Cancer Care (Engl) 2010, 19(6):755-760. Epub 2009/08/28
  • [23]Fizazi K, Carducci M, Smith M, Damiao R, Brown J, Karsh L, Milecki P, Shore N, Rader M, Wang H, Jiang Q, Tadros S, Dansey R, Goessl C: Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet 2011, 377(9768):813-822. Epub 2011/03/01
  • [24]Smith MR, Saad F, Coleman R, Shore N, Fizazi K, Tombal B, Miller K, Sieber P, Karsh L, Damiao R, Tammela TL, Egerdie B, Van Poppel H, Chin J, Morote J, Gomez-Veiga F, Borkowski T, Ye Z, Kupic A, Dansey R, Goessl C: Denosumab and bone-metastasis-free survival in men with castration-resistant prostate cancer: results of a phase 3, randomised, placebo-controlled trial. Lancet 2012, 379(9810):39-46. Epub 2011/11/19
  • [25]Carter JA, Botteman MF: Health-economic review of zoledronic acid for the management of skeletal-related events in bone-metastatic prostate cancer. Expert Rev Pharmacoecon Outcomes Res 2012, 12(4):425-437. Epub 2012/05/01
  • [26]Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, Oudard S, Theodore C, James ND, Turesson I, Rosenthal MA, Eisenberger MA: Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 2004, 351(15):1502-1512. Epub 2004/10/08
  • [27]Petrylak DP, Tangen CM, Hussain MH, Lara PN Jr, Jones JA, Taplin ME, Burch PA, Berry D, Moinpour C, Kohli M, Benson MC, Small EJ, Raghavan D, Crawford ED: Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med 2004, 351(15):1513-1520. Epub 2004/10/08
  • [28]Tannock IF, Osoba D, Stockler MR, Ernst DS, Neville AJ, Moore MJ, Armitage GR, Wilson JJ, Venner PM, Coppin CM, Murphy KC: Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormone-resistant prostate cancer: a Canadian randomized trial with palliative end points. J Clin Oncol 1996, 14(6):1756-1764. Epub 1996/06/01
  • [29]Saad F, Hotte SJ: Guidelines for the management of castrate-resistant prostate cancer. Can Urol Assoc J 2010, 4(6):380-384. Epub 2010/12/31
  • [30]Saad F, Hotte S, Catton C, Drachenberg D, Finelli A, Fleshner N, Gleave M, Kapoor A, Kassouf W, Loblaw A, North S, Usmani N, Chi KN: CUA-CUOG guidelines for the management of castration-resistant prostate cancer (CRPC): 2013 update. Can Urol Assoc J 2013, 7(7–8):231-237. Epub 2013/09/14
  • [31]Eymard JC, Oudard S, Gravis G, Ferrero JM, Theodore C, Joly F, Priou F, Krakowski I, Zannetti A, Thill L, Beuzeboc P: Docetaxel reintroduction in patients with metastatic castration-resistant docetaxel-sensitive prostate cancer: a retrospective multicentre study. BJU Int 2010, 106(7):974-978. Epub 2010/03/17
  • [32]Ansari J, Hussain SA, Zarkar A, Tanguay JS, Bliss J, Glaholm J: Docetaxel chemotherapy for metastatic hormone refractory prostate cancer as first-line palliative chemotherapy and subsequent re-treatment: Birmingham experience. Oncol Rep 2008, 20(4):891-896. Epub 2008/09/25
  • [33]Shore N, Mason M, de Reijke TM: New developments in castrate-resistant prostate cancer. BJU Int 2012, 109(Suppl 6):22-32. Epub 2012/06/15
  • [34]de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, Chi KN, Jones RJ, Goodman OB Jr, Saad F, Staffurth JN, Mainwaring P, Harland S, Flaig TW, Hutson TE, Cheng T, Patterson H, Hainsworth JD, Ryan CJ, Sternberg CN, Ellard SL, Flechon A, Saleh M, Scholz M, Efstathiou E, Zivi A, Bianchini D, Loriot Y, Chieffo N, Kheoh T, et al.: Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 2011, 364(21):1995-2005. Epub 2011/05/27
  • [35]Oudard S: TROPIC: Phase III trial of cabazitaxel for the treatment of metastatic castration-resistant prostate cancer. Future Oncol 2011, 7(4):497-506. Epub 2011/04/06
  • [36]de Bono JS, Oudard S, Ozguroglu M, Hansen S, Machiels JP, Kocak I, Gravis G, Bodrogi I, Mackenzie MJ, Shen L, Roessner M, Gupta S, Sartor AO: Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet 2010, 376(9747):1147-1154. Epub 2010/10/05
  • [37]Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, de Wit R, Mulders P, Chi KN, Shore ND, Armstrong AJ, Flaig TW, Flechon A, Mainwaring P, Fleming M, Hainsworth JD, Hirmand M, Selby B, Seely L, de Bono JS: Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med 2012, 367(13):1187-1197. Epub 2012/08/17
  • [38]Institut national d'excellence en santé et en services sociaux: JEVTANAMC – Cancer de la prostate, Avis de refus. Quebec, QC: Institut national d'excellence en santé et en services sociaux; 2012.
  • [39]Institut national d'excellence en santé et en services sociaux: ZYTIGAMC – Cancer de la prostate. PROJET PILOTE EN ONCOLOGIE: Avis de refus à défaut d’une entente de partage de risques financiers. Quebec, QC: Institut national d'excellence en santé et en services sociaux; 2012.
  • [40]Sarosdy MF, Schellhammer PF, Soloway MS, Vogelzang NJ, Crawford ED, Presti J, Chodak GW, Mitchell P, Porter L: Endocrine effects, efficacy and tolerability of a 10.8-mg depot formulation of goserelin acetate administered every 13 weeks to patients with advanced prostate cancer. BJU Int 1999, 83(7):801-806. Epub 1999/06/15
  • [41]Hunink MGM, Glasziou PP, Siegel JE, Weeks JC, Pliskin JS, Elstein AS, Weinstein MC: Decision Making in Health and Medicine: Interpreting Evidence and Values. Cambridge: Cambridge University Press; 2001.
  • [42]Régie de l'Assurance Maladie du Québec (RAMQ): Liste de médicaments assurés. In Édition 34 - 1er février 2012. Québec,QC: Régie de l'Assurance Maladie du Québec; 2012.
  • [43]Karnon J, Stahl J, Brennan A, Caro JJ, Mar J, Moller J: Modeling using Discrete Event Simulation: A Report of the ISPOR-SMDM Modeling Good Research Practices Task Force-4. Value Health 2012, 15(6):821-827. Epub 2012/09/25
  • [44]Hollingworth W, Spackman DE: Emerging methods in economic modeling of imaging costs and outcomes a short report on discrete event simulation. Acad Radiol 2007, 14(4):406-410. Epub 2007/03/21
  • [45]Caro JJ, Moller J, Getsios D: Discrete event simulation: the preferred technique for health economic evaluations? Value Health 2010, 13(8):1056-1060. Epub 2010/09/10
  • [46]Montreal General Hospital: Pharmacy list. Montreal, QC: McGill University Health Center; 2013.
  • [47]Collins R, Fenwick E, Trowman R, Perard R, Norman G, Light K, Birtle A, Palmer S, Riemsma R: A systematic review and economic model of the clinical effectiveness and cost-effectiveness of docetaxel in combination with prednisone or prednisolone for the treatment of hormone-refractory metastatic prostate cancer. Health Technol Assess 2007, 11(2):iii-iv. xv-xviii, 1–179. Epub 2006/12/22
  • [48]Krahn MD, Zagorski B, Laporte A, Alibhai SM, Bremner KE, Tomlinson G, Warde P, Naglie G: Healthcare costs associated with prostate cancer: estimates from a population-based study. BJU Int 2010, 105(3):338-346. Epub 2009/07/15
  • [49]Grover SA, Coupal L, Zowall H, Rajan R, Trachtenberg J, Elhilali M, Chetner M, Goldenberg L: The economic burden of prostate cancer in Canada: forecasts from the Montreal Prostate Cancer Model. CMAJ 2000, 162(7):987-992. Epub 2000/04/14
  • [50]Alemayehu B, Buysman E, Parry D, Becker L, Nathan F: Economic burden and healthcare utilization associated with castration-resistant prostate cancer in a commercial and Medicare Advantage US patient population. J Med Econ 2010, 13(2):351-361. Epub 2010/05/25
  • [51]Mehra M, Wu Y, Dhawan R: Healthcare resource use in advanced prostate cancer patients treated with docetaxel. J Med Econ 2012, 15(5):836-843. Epub 2012/04/03
  • [52]Crawford ED, Flaig TW: Optimizing outcomes of advanced prostate cancer: drug sequencing and novel therapeutic approaches. Oncology (Williston Park) 2012, 26(1):70-77. Epub 2012/03/08
  • [53]Kaku T, Hitaka T, Ojida A, Matsunaga N, Adachi M, Tanaka T, Hara T, Yamaoka M, Kusaka M, Okuda T, Asahi S, Furuya S, Tasaka A: Discovery of orteronel (TAK-700), a naphthylmethylimidazole derivative, as a highly selective 17,20-lyase inhibitor with potential utility in the treatment of prostate cancer. Bioorg Med Chem 2011, 19(21):6383-6399. Epub 2011/10/08
  • [54]Parker C, Nilsson S, Heinrich D, Helle SI, O'Sullivan JM, Fossa SD, Chodacki A, Wiechno P, Logue J, Seke M, Widmark A, Johannessen DC, Hoskin P, Bottomley D, James ND, Solberg A, Syndikus I, Kliment J, Wedel S, Boehmer S, Dall'Oglio M, Franzen L, Coleman R, Vogelzang NJ, O'Bryan-Tear CG, Staudacher K, Garcia-Vargas J, Shan M, Bruland OS, Sartor O: Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med 2013, 369(3):213-223. Epub 2013/07/19
  • [55]Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, Redfern CH, Ferrari AC, Dreicer R, Sims RB, Xu Y, Frohlich MW, Schellhammer PF: Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 2010, 363(5):411-422. Epub 2010/09/08
  • [56]Aragon-Ching JB, Madan RA, Dahut WL: Angiogenesis inhibition in prostate cancer: current uses and future promises. J Oncol 2010, 2010:361836. Epub 2010/02/20
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