臨床泌尿器科65巻11号

2011年10月発行

綜説

浸潤性膀胱癌に対する化学療法，および，新規膀胱温存療法“OMC-Regimen”の治療効果

著者： 東治人¹ 稲元輝生¹ 小山耕平² 濱田修二³ 安倍弘一⁴ 古武彌嗣⁵ 増田裕⁶ 木山賢⁷ 坂元武⁸ 和辻利一⁹ 能見勇人¹ 右梅貴信¹ 山本和宏⁹ 鳴海善文⁹

所属機関： ¹大阪医科大学泌尿器科 ²北摂病院泌尿器科 ³済生会茨木病院泌尿器科 ⁴済生会中津病院泌尿器科 ⁵済生会静岡病院泌尿器科 ⁶藍野病院泌尿器科 ⁷城山病院泌尿器科 ⁸加納病院泌尿器科 ⁹枚方市民病院泌尿器科

ページ範囲：P.809 - P.819

文献概要

要旨　局所浸潤性膀胱癌に対する標準治療は根治的膀胱全摘術であるが，術後のQOL低下は大きな問題であり，また，手術を施行しても5年生存率は60％に満たず，治療効果の高い（膀胱全摘を凌ぐ）膀胱温存療法を開発することは，今後の浸潤性膀胱癌の治療において極めて重要である。本稿では，これまで多くの施設で行われてきた化学療法（ネオアジュバント，あるいは，アジュバント），および，化学放射線療法の歴史的変遷と治療成績，そして，われわれが15年前から行っている新規膀胱温存療法“OMC-regimen”における治療方法の詳細，治療成績，および今後の展望について解説する。

参考文献

1）Stein JP, Lieskovsky G, Cote R, et al：Radical cystectomy in the treatment of invasive bladder cancer：long-term results in 1,054 patients. J Clin Oncol 19：666-675, 2001

2）Pagano F, Bassi P, Galetti TP, et al：Results of contemporary radical cystectomy for invasive bladder cancer：a clinicopathological study with an emphasis on the inadequacy of the tumor, nodes and metastases classification. J Urol 145：45-50, 1991

3）Shariat SF, Karakiewicz PI, Palapattu GS, et al：Outcomes of radical cystectomy for transitional cell carcinoma of the bladder：a contemporary series from the Bladder Cancer Research Consortium. J Urol 176：2414-2422；discussion 2422, 2006

4）Azuma H, Kotake Y, Yamamoto K, et al：Effect of combined therapy using balloon-occluded arterial infusion of cisplatin and hemodialysis with concurrent radiation for locally invasive bladder cancer. Am J Clin Oncol 31：11-21, 2008

5）Azuma H, Yamamoto K, Inamoto T, et al：Total cystectomy versus bladder preservation therapy for locally invasive bladder cancer：effect of combined therapy using balloon-occluded arterial infusion of anticancer agent and hemodialysis with concurrent radiation. Am J Clin Oncol 12：592-606, 2009

6）Azuma H, Inamoto T, Ibuki N, et al：Novel bladder preservation therapy for locally invasive bladder cancer：combined therapy using balloon-occluded arterial infusion of anticancer agent and hemodialysis with concurrent radiation. Int J Oncol 37：773-785, 2010

7）Azuma H, Inamoto T, Ibuki N, et al：Utility of the novel bladder preservation therapy, BOAI-CDDP-radiation（OMC-regimen）, for elderly patients with invasive bladder cancer. Int J Oncol 38：13-24, 2011

8）Loehrer PJ, Einhorn LH, Elson PJ, et al：A randomized comparison of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma：a cooperative group study. J Clin Oncol 10：1066-1073, 1992

9）Logothetis CJ, Dexeus FH, Finn L, et al：A prospective randomized trial comparing MVAC and CISCA chemotherapy for patients with metastatic urothelial tumors. J Clin Oncol 8：1050-1055, 1990

10）von der Maase H, Sengelov L, Roberts JT, et al：Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol 23：4602-4608, 2005

11）von der Maase H, Hansen SW, Roberts JT, et al：Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer：results of a large, randomized, multinational, multicenter, phase Ⅲ study. J Clin Oncol 18：3068-3077, 2000

12）Sternberg CN, Yagoda A, Scher HI, et al：Methotrexate, vinblastine, doxorubicin, and cisplatin for advanced transitional cell carcinoma of the urothelium. efficacy and patterns of response and relapse. Cancer 64：2448-2458, 1989

13）Saxman SB, Propert KJ, Einhorn LH, et al：Long-term follow-up of a phase Ⅲ intergroup study of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma：a cooperative group study. J Clin Oncol 15：2564-2569, 1997

14）Teramukai S, Nishiyama H, Matsui Y, et al：Evaluation for surrogacy of end points by using data from observational studies：tumor downstaging for evaluating neoadjuvant chemotherapy in invasive bladder cancer. Clin Cancer Res 12：139-143, 2006

15）Calabro F and Sternberg CN：Neoadjuvant and adjuvant chemotherapy in muscle-invasive bladder cancer. Eur Urol 55：348-358, 2009

16）Grossman HB, Natale RB, Tangen CM, et al：Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med 349：859-866, 2003

17）Neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer：a randomised controlled trial. International collaboration of trialists. Lancet 354：533-540, 1999

18）Advanced Bladder Cancer（ABC）Meta-analysis Collaboration：Neoadjuvant chemotherapy in invasive bladder cancer：a systematic review and meta-analysis. Lancet 361：1927-1934, 2003

19）Advanced Bladder Cancer（ABC）Meta-analysis Collaboration：Neoadjuvant chemotherapy in invasive bladder cancer：update of a systematic review and meta-analysis of individual patient data advanced bladder cancer（ABC）meta-analysis collaboration. Eur Urol 48：202-205；discussion 205-206, 2005

20）Winquist E, Kirchner TS, Segal R, et al：Neoadjuvant chemotherapy for transitional cell carcinoma of the bladder：a systematic review and meta-analysis. J Urol 171：561-569, 2004

21）Lee CT, Madii R, Daignault S, et al：Cystectomy delay more than 3 months from initial bladder cancer diagnosis results in decreased disease specific and overall survival. J Urol 175：1262-1267；discussion 1267, 2006

22）Fahmy NM, Mahmud S and Aprikian AG：Delay in the surgical treatment of bladder cancer and survival：systematic review of the literature. Eur Urol 50：1176-1182, 2006

23）Sanchez-Ortiz RF, Huang WC, Mick R, et al：An interval longer than 12 weeks between the diagnosis of muscle invasion and cystectomy is associated with worse outcome in bladder carcinoma. J Urol 169：110-115；discussion 115, 2003

24）Skinner DG, Daniels JR, Russell CA, et al：The role of adjuvant chemotherapy following cystectomy for invasive bladder cancer：a prospective comparative trial. J Urol 145：459-464；discussion 464-457, 1991

25）Stockle M, Meyenburg W, Wellek S, et al：Adjuvant polychemotherapy of nonorgan-confined bladder cancer after radical cystectomy revisited：long-term results of a controlled prospective study and further clinical experience. J Urol 153：47-52, 1995

26）Freiha F, Reese J and Torti FM：A randomized trial of radical cystectomy versus radical cystectomy plus cisplatin, vinblastine and methotrexate chemotherapy for muscle invasive bladder cancer. J Urol 155：495-499；discussion 499-500, 1996

27）Adjuvant chemotherapy in invasive bladder cancer：a systematic review and meta-analysis of individual patient data Advanced Bladder Cancer（ABC）Meta-analysis Collaboration. Eur Urol 48：189-199；discussion 199-201, 2005

28）Stockle M, Meyenburg W, Wellek S, et al：Advanced bladder cancer（stages pT3b, pT4a, pN1 and pN2）：improved survival after radical cystectomy and 3 adjuvant cycles of chemotherapy：results of a controlled prospective study. J Urol 148：302-306；discussion 306-307, 1992

29）Lehmann J, Franzaring L, Thuroff J, et al：Complete long-term survival data from a trial of adjuvant chemotherapy vs control after radical cystectomy for locally advanced bladder cancer. BJU Int 97：42-47, 2006

30）Suttmann H, Kamradt J, Lehmann J, et al：Improving the prognosis of patients after radical cystectomy. Part Ⅱ：the role of perioperative chemotherapy. BJU Int 100：1225-1228, 2007

31）Tester W, Porter A, Asbell S, et al：Combined modality program with possible organ preservation for invasive bladder carcinoma：results of RTOG protocol 85-12. Int J Radiat Oncol Biol Phys 25：783-790, 1993

32）Tester W, Caplan R, Heaney J, et al：Neoadjuvant combined modality program with selective organ preservation for invasive bladder cancer：results of Radiation Therapy Oncology Group phase Ⅱ trial 8802. J Clin Oncol 14：119-126, 1996

33）Shipley WU, Winter KA, Kaufman DS, et al：Phase Ⅲ trial of neoadjuvant chemotherapy in patients with invasive bladder cancer treated with selective bladder preservation by combined radiation therapy and chemotherapy：initial results of Radiation Therapy Oncology Group 89-03. J Clin Oncol 16：3576-3583, 1998

34）Kaufman DS, Winter KA, Shipley WU, et al：The initial results in muscle-invading bladder cancer of RTOG 95-06：phase Ⅰ/Ⅱ trial of transurethral surgery plus radiation therapy with concurrent cisplatin and 5-fluorouracil followed by selective bladder preservation or cystectomy depending on the initial response. Oncologist 5：471-476, 2000

35）Hagan MP, Winter KA, Kaufman DS, et al：RTOG 97-06：initial report of a phase Ⅰ-Ⅱ trial of selective bladder conservation using TURBT, twice-daily accelerated irradiation sensitized with cisplatin, and adjuvant MCV combination chemotherapy. Int J Radiat Oncol Biol Phys 57：665-672, 2003

36）Kaufman DS, Winter KA, Shipley WU, et al：Phase Ⅰ-Ⅱ RTOG study（99-06）of patients with muscle-invasive bladder cancer undergoing transurethral surgery, paclitaxel, cisplatin, and twice-daily radiotherapy followed by selective bladder preservation or radical cystectomy and adjuvant chemotherapy. Urology 73：833-837, 2009

37）Gogna NK, Matthews JH, Turner SL, et al：Efficacy and tolerability of concurrent weekly low dose cisplatin during radiation treatment of localised muscle invasive bladder transitional cell carcinoma：a report of two sequential Phase Ⅱ studies from the Trans Tasman Radiation Oncology Group. Radiother Oncol 81：9-17, 2006

38）Shipley WU, Prout GRJ, Einstein AB, et al：Treatment of invasive bladder cancer by cisplatin and radiation in patients unsuited for surgery. JAMA 258：931-935, 1987

39）Prout GRJ, Shipley WU, Kaufman DS, et al：Preliminary results in invasive bladder cancer with transurethral resection, neoadjuvant chemotherapy and combined pelvic irradiation plus cisplatin chemotherapy. J Urol 144：1128-1136, 1990

40）Sauer R, Dunst J, Altendorf-Hofmann A, et al：Radiotherapy with and without cisplatin in bladder cancer. Int J Radiat Oncol Biol Phys 19：687-691, 1990

41）Zietman AL, Grocela J, Zehr E, et al：Selective bladder conservation using transurethral resection, chemotherapy, and radiation：management and consequences of Ta, T1, and Tis recurrence within the retained bladder. Urology 58：380-385, 2001

42）Rodel C, Grabenbauer GG, Kuhn R, et al：Combined-modality treatment and selective organ preservation in invasive bladder cancer：long-term results. J Clin Oncol 20：3061-3071, 2002

43）Chen WC, Liaw CC, Chuang CK, et al：Concurrent cisplatin, 5-fluorouracil, leucovorin, and radiotherapy for invasive bladder cancer. Int J Radiat Oncol Biol Phys 56：726-733, 2003

44）Peyromaure M, Slama J, Beuzeboc P, et al：Concurrent chemoradiotherapy for clinical stage T2 bladder cancer：report of a single institution. Urology 63：73-77, 2004

45）Weiss C, Engehausen DG, Krause FS, et al：Radiochemotherapy with cisplatin and 5-fluorouracil after transurethral surgery in patients with bladder cancer. Int J Radiat Oncol Biol Phys 68：1072-1080, 2007

46）Gospodarowicz M：Radiotherapy and organ preservation in bladder cancer：are we ignoring the evidence? J Clin Oncol 20：3048-3050, 2002

47）Choueiri TK and Raghavan D：Chemotherapy for muscle-invasive bladder cancer treated with definitive radiotherapy：persisting uncertainlies. Nature Clinical practice Oncology 5：444-454, 2008

48）Weiss C, Wittlinger M, Engehausen DG, et al：Management of superficial recurrences in an irradiated bladder after combined-modality organ-preserving therapy. Int J Radiat Oncol Biol Phys 70：1502-1506, 2008

49）Shipley WS, Kaufman DS, Heney NM, et al：An update of combined modality therapy for patients with muscle invading bladder cancer using selective bladder preservation or cystectomy. J Urol 162：445-451, 1999

50）Leissner J, Koeppen C and Wolf H：Prognostic significance of vascular and perineural invasion in urothelial bladder cancer treated with radical cystectomy. J Urol 169：955-960, 2003

51）Weiss C, Rödelm F, Wolf I, et al：Combined-modality treatment and organ preservation in bladder cancer：do molecular markers predict outcome? Strahlenther Onkol 181：213-222, 2005

52）Weizer AZ, Joshi D, Daignault S, et al：Performance status is a predictor of overall survival of elderly patients with muscle invasive bladder cancer. J Urol 177：1287-1293, 2007

53）Eapen L, Stewart D, Danjoux C, et al：Intraarterial cisplatin and concurrent radiation for locally advanced bladder cancer. J Clin Oncol 7：230-235, 1989

54）Klopp CT, Alford TC, Bateman J, et al：Fractionated intraarterial cancer chemotherapy with methyl bisamine hydrochloride：a preliminary report. Ann Surg 132：811-832, 1950

55）Chen H-SG and Gross JF：Intra-arterial infusion of anticancer drugs：theoretic aspects of drug delivery and review of responses. Cancer Treat Rep 64：31-40, 1980

56）Terashima Y：CDDP concentration of bladder tumors：comparison between intraarterial infusion and intravenous infusion. Nippon Gan Chiryo Gakkai Shi 23：859-866, 1988

57）Higa I, Hayakawa M, Shishido S, et al：Therapeutic and experimental and clinical results of intra-arterial infusion chemotherapy for the treatment of advanced bladder carcinoma. Nishinihon J Urol 52, 1990

58）Douple EB and Richmond RC：A review of platinum complex biochemistry suggests a rationale for combined platinum-radiotherapy. Int J Radiat Oncol Biol Phys 8：1335-1339, 1979

59）Abbott DW, Freeman ML and Holt JT：Double-strand break repair deficiency and radiation sensitivity in BRCA2 mutant cancer cells. J Natl Cancer Inst 90：978-985, 1998

60）Brown JM and Wouters BG：Apoptosis, p53, and tumor cell sensitivity to anticancer agents. Cancer Res 59：1391-1399, 1999

61）Mokarim A, Uetani M, Hayashi N, et al：Combined intraarterial chemotherapy and radiotherapy in the treatment of bladder carcinoma. Cancer 80：1776-1785, 1997

62）Sumiyoshi Y：Chemoradiotherapy as a bladder-preservation approach for muscle-invasive bladder cancer：current status and perspectives. Int J Clin Oncol 9：484-490, 2004

63）Miyanaga N, Akaza H, Hinotsu S, et al：Background variables for the patients with invasive bladder cancer suitable for bladder-preserving therapy. Jpn J Clin Oncol 37：852-857, 2007

64）Eapen L, Stewart D and Crook J：Intraarterial cisplatin（IAC）and concurrent radiation（PR）in the management of transitional bladder cancer：an organ preservation strategy. Proc Am Soc Clin Oncol 14：238, 1995

65）Aota Y and Yoshida K：Intra-arterial chemotherapy for locally advanced bladder cancer. Hinyokika Kiyo 45：149-153, 1999

66）Eapen L, Stewart D, Collins J, et al：Effective bladder sparing therapy with intra-arterial cisplatin and radiotherapy for localized bladder cancer. J Urol 172：1276-1280, 2004