臨床泌尿器科60巻3号

2006年03月発行

綜説

再燃前立腺癌におけるドセタキセル療法の現状と展望

著者： 島居徹¹ 赤座英之¹

所属機関： ¹筑波大学大学院人間総合科学研究科臨床医学系泌尿器科

ページ範囲：P.177 - P.187

文献概要

要旨　ホルモン療法抵抗性の前立腺癌の治療戦略は限られており，特に化学療法剤に関しては従来有効性が乏しいと考えられてきた。しかし，近年，再燃前立腺癌に対するタキサン系薬剤を用いた治療の良好な成績が報告されている。タキサン系薬剤はヨーロッパイチイの針葉から抽出，半合成された抗癌剤であり，作用はtubulin重合促進による微小管安定と紡錘体形成阻害による細胞分裂の停止である。またbcl-2蛋白のリン酸化によるアポトーシス抑制作用の阻害によるアポトーシス誘導もあり，各種固形癌に対し単剤でも高い奏効率を示すとされている。このタキサン系薬剤はパクリタキセル，ドセタキセルに代表され，単剤治療，硫酸エストラムスチンなどとの併用療法が行われているが，2004年にドセタキセル3週ごとの投与とプレドニゾロンとの併用療法が生存率に寄与するとされ，米国Food and Drug Administration（FDA）により承認された。本邦ではこのドセタキセルについてはホルモン不応性前立腺癌の第Ⅱ相臨床試験が進行中であるが，欧米の成績に匹敵する治療成績が報告されつつある。また最近，このドセタキセル治療を前立腺全摘症例のなかのハイリスク群や，局所進行群に対してネオアジュバント療法として用いる報告もみられている。さらに，分子標的薬との併用による臨床試験なども実施されており，今後が期待される化学療法剤と考えられる。

参考文献

1）日本泌尿器科学会，日本病理学会（編）：前立腺癌取扱い規約（第3版）．金原出版，2001

2）Scher HI, Steineck G, Kelly WK：Hormone-refractory（D3）prostate cancer：Refining the concept. Urology 46：142-148, 1995

3）Pienta KJ, Redman B, Hussain M, et al：PhaseⅡ evaluation of oral estramustine and oral etoposide in hormone-refractory adenocarcinoma of the prostate. J Clin Oncol 12：2005-2012, 1994

4）Kelly WK, Scher HI, Mazumdar M, et al：Prostate-specific antigen as a measure of disease outcome in metastatic hormone-refractory prostate cancer. J Clin Oncol 11：607-615, 1993

5）Smith DC, Chay CH, Dunn RL, et al：PhaseⅡ trial of paclitaxel, estramustine, etoposide, and carboplatin in the treatment of patients with hormone-refractory prostate carcinoma. Cancer 98：269-276, 2003

6）Haas N, Roth B, Garay C, et al：PhaseⅠ trial of weekly paclitaxel plus oral estramustine phosphate in patients with hormone-refractory prostate cancer. Urology 58：59-64, 2001

7）Ferrari AC, Chachoua A, Singh H, et al：PhaseⅠ/Ⅱ study of weekly paclitaxel and 3 days of high dose oral estramustine in patients with hormone-refractory prostate carcinoma. Cancer 91：2039-2045, 2001

8）Kuzel TM, Kies MS, Wu N, et al：PhaseⅠ trial of oral estramustine and 3-hr infusional paclitaxel for the treatment of hormone refractory prostate cancer. Cancer Invest 20：634-643, 2002

9）Kuruma H, Fujita T, Shitara T, et al：Weekly paclitaxel plus estramustine combination therapy in hormone-refractory prostate cancer：a pilot study. Int J Urol 10：470-475, 2003

10）Vaughn DJ, Brown AW Jr, Harker WG, et al：Multicenter phaseⅡ study of estramustine phosphate plus weekly paclitaxel in patients with androgen-independent prostate carcinoma. Cancer 100：746-750, 2004

11）Meluch AA, Greco FA, Morrissey LH, et al：Minnie Pearl Cancer Research Network. Weekly paclitaxel, estramustine phosphate, and oral etoposide in the treatment of hormone-refractory prostate carcinoma：results of a Minnie Pearl Cancer Research Network phaseⅡ trial. Cancer 98：2192-2198, 2003

12）Millikan R, Thall PF, Lee SJ, et al：Randomized, multicenter, phaseⅡ trial of two multicomponent regimens in androgen-independent prostate cancer J Clin Oncol 21：878-883, 2003

13）Urakami S, Igawa M, Kikuno N, et al：Combination chemotherapy with paclitaxel, estramustine and carboplatin for hormone refractory prostate cancer. J Urol 168：2444-2450, 2002

14）Kelly WK, Curley T, Slovin S, et al：Paclitaxel, estramustine phosphate, and carboplatin in patients with advanced prostate cancer. J Clin Oncol 19：44-53, 2001

15）Kelly WK, Zhu AX, Scher H, et al：Dose escalation study of intravenous estramustine phosphate in combination with paclitaxel and carboplatin in patients with advanced prostate cancer. Clin Cancer Res 9：2098-2107, 2003

16）Smith DC, Esper P, Strawderman M, et al：PhaseⅡ trial of oral estramustine, oral etoposide, and intravenous paclitaxel in hormone-refractory prostate cancer. J Clin Oncol 17：1664-1671, 1999

17）Roth BJ, Yeap BY, Wilding G, et al：Taxol in advanced, hormone-refractory carcinoma of the prostate. A phaseⅡ trial of the Eastern Cooperative Oncology Group. Cancer 72：2457-2460, 1993

18）Trivedi C, Redman B, Flaherty LE, et al：Weekly 1-hour infusion of paclitaxel. Clinical feasibility and efficacy in patients with hormone-refractory prostate carcinoma. Cancer 89：431-436, 2000 Erratum in：Cancer 89：1412, 2000

19）Urakami S, Yoshino T, Kikuno N, et al：Docetaxel-based chemotherapy as second-line treatment for paclitaxel-based chemotherapy-resistant hormone-refractory prostate cancer：a pilot study. Urology 65：543-548, 2005

20）Ringel I, Horwitz SB：Studies with RP 56976（taxotere）a semisynthetic analogue of taxol. J Natl Cancer Inst 83：288-291, 1991

21）Kreis W, Budman DR, Calabro A：Unique synergism or antagonism of combinations of chemotherapeutic and hormonal agents in human prostate cancer cell lines. Br J Urol 79：196-202, 1997

22）Savarese DM, Halabi S, Hars V, et al：PhaseⅡ study of docetaxel, estramustine, and low-dose hydrocortisone in men with hormone-refractory prostate cancer：a final report of CALGB 9780. Cancer and Leukemia Group B. J Clin Oncol 19：2509-2516, 2001

23）Picus J, Schultz M：Docetaxel（Taxotere）as monotherapy in the treatment of hormone-refractory prostate cancer：preliminary results. Semin Oncol 26（5 Suppl 17）：14-18, 1999

24）Friedland D, Cohen J, Miller R Jr, et al：A phaseⅡ trial of docetaxel（Taxotere）in hormone-refractory prostate cancer：correlation of antitumor effect to phosphorylation of Bcl-2. Semin Oncol 26（5 Suppl 17）：19-23, 1999

25）Berry W, Dakhil S, Gregurich MA, et al：PhaseⅡ trial of single-agent weekly docetaxel in hormone-refractory, symptomatic, metastatic carcinoma of the prostate. Semin Oncol 28（Suppl 15）：8-15, 2001

26）Beer TM, Pierce WC, Lowe BA, et al：PhaseⅡ study of weekly docetaxel in symptomatic androgen-independent prostate cancer. Ann Oncol 12：1273-1279, 2001

27）Gravis G, Bladou F, Salem N, et al：Weekly administration of docetaxel for symptomatic metastatic hormone-refractory prostate carcinoma. Cancer 98：1627-1634, 2003

28）Kojima T, Shimazui T, Onozawa M, et al：Weekly administration of docetaxel in patients with hormone-refractory prostate cancer：a pilot study on Japanese patients. Jpn J Clin Oncol 34：137-141, 2004

29）島居　徹，赤座英之：Taxane系薬剤による再燃前立腺癌の治療．第63回日本癌学会総会シンポジウム．2004年9月

30）Petrylak DP, Tangen CM, Hussain MH, et al：Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 351：1502-1512, 2004

31）島居　徹，河合弘二，小島崇宏，他：ホルモン抵抗性前立腺癌に対するドセタキセル，プレドニゾロン併用療法．日癌治療会誌40：42，2005

32）Kreis W, Budman DR, Fetten J, et al：PhaseⅠ trial of the combination of daily estramustine phosphate and intermittent docetaxel in patients with metastatic hormone refractory prostate carcinoma. Ann Oncol 10：33-38, 1999

33）Petrylak DP, Macarthur RB, O'Connor J, et al：PhaseⅠ trial of docetaxel with estramustine in androgen-independent prostate cancer. J Clin Oncol 17：958-967, 1999

34）Sinibaldi VJ, Carducci MA, Moore-Cooper S, et al：PhaseⅡ evaluation of docetaxel plus one-day oral extramustine phosphate in the treatment of patients with androgen independent prostate carcinoma. Cancer 94：1457-1465, 2002

35）Petrylak DP, Tangen CM, Hussain MH, et al：Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med 351：1513-520, 2004

36）Beer TM, Hough KM, Garzotto M, et al：Weekly high-dose calcitriol and docetaxel in advanced prostate cancer. Semin Oncol 28（Suppl 15）：49-55, 2001

37）Mathew P, Thall PF, Jones D, et al：Platelet-derived growth factor receptor inhibitor imatinib mesylate and docetaxel：a modular phaseⅠ trial in androgen-independent prostate cancer. J Clin Oncol 22：3323-3329, 2004

38）Tannock IF, Osoba D, Stockler MR, et al：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 14：1756-1764, 1996

39）島居　徹，赤座英之，吉川裕之，他：本邦における腹部外科手術後の静脈血栓塞栓症（VTE）の発生に関する前向き疫学調査．第26回日本血栓止血学会コンセンサスシンポジウム．Medical Tribune 2003年12月18日

40）Amstrong AJ, Carducci MA：Chemotherapy for advanced prostate cancer：results of new clinical trials and future studies. Curr Oncol Rep 7：220-227, 2005

41）Tannock I, Gospodarowicz M, Meakin W, et al：Treatment of metastatic prostatic cancer with low-dose prednisone：evaluation of pain and quality of life as pragmatic indices of response. J Clin Oncol 7：590-597, 1989

42）Fossa SD, Slee PH, Brausi M, et al：Flutamide versus prednisone in patients with prostate cancer symptomatically progressing after androgen-ablative therapy：a phaseⅢ study of the European organization for research and treatment of cancer genitourinary group. J Clin Oncol 19：62-71, 2001

43）Nishimura K, Nonomura N, Satoh E, et al：Potential mechanism for the effects of dexamethasone on growth of androgen-independent prostate cancer. J Natl Cancer Inst 93：1739-1746, 2001

44）Kantoff PW, Halabi S, Conaway M, et al：Hydrocortisone with or without mitoxantrone in men with hormone-refractory prostate cancer：results of the cancer and leukemia group B 9182 study. J Clin Oncol 17：2506-2513, 1999

45）Berry W, Dakhil S, Modiano M, et al：PhaseⅢ study of mitoxantrone plus low dose predonisone versus low dose predonisone alone in patients with asymptomatic hormone refractory prostate cancer. J Urol 168：2439-2443, 2002

46）Small EJ, Meyer M, Marshall ME, et al：Suramin therapy for patients with symptomatic hormone-refractory prostate cancer：results of a ramdomized phaseⅢ trial comparing suramin plus hydrocortisone to placebo plus hydrocortisone. J Clin Oncol 18：1440-1450, 2000

47）Li Y, Hong X, Hussain M, et al：Gene expression profiling revealed novel molecular targets of docetaxel and estramustine combination treatment in prostate cancer cells. Mol Cancer Ther 4：389-398, 2005

48）Dreicer R, Magi-Galluzzi C, Zhou M, et al：PhaseⅡ trial of neoadjuvant docetaxel before radical prostatectomy for locally advanced prostate cancer. Urology 63：1138-1142, 2004

49）Febbo PG, Richie JP, George DJ, et al：Neoadjuvant docetaxel before radical prostatectomy in patients with high-risk localized prostate cancer. Clin Cancer Res 11：5233-5240, 2005

50）Beer TM, Eilers KM, Garzotto M, et al：Weekly high dose calciriol and docetaxel in metastatic androgen-independent prostate cancer. J Clin Oncol 21：123-128, 2003

51）Chatta GS, Fakih M, Ramalingam S, et al：PhaseⅠ pharmacokinetic study of daily imatinib in combination with docetaxel for patients with advanced solid tumors［abstract］. Proc ASCO 23：2047, 2004

52）Picus J, Halabi S, Rini B, et al：The use of bevacizumab with docetaxel and estramustine in hormone refractory prostate cancer：initial results of CALGB 90006［abstract］. Proc ASCO 22：393, 2003

53）Carducci M, Nelson JB, Saad F：Effects of atrasentan on disease progression and biological markers in men with metastatic hormone-refractory prostate cancer：phase 3 study［abstract］. Proc ASCO 23：4508, 2004