臨床婦人科産科67巻11号

2013年11月発行

今月の臨床 進行婦人科がんの集学的治療

子宮体がん

2．再発子宮体がんの治療戦略

著者： 長谷川清志¹ 塚田和彦¹ 多田伸¹

所属機関： ¹藤田保健衛生大学坂文種報徳會病院産婦人科

ページ範囲：P.1123 - P.1138

文献概要

●子宮体がんは再発した場合のMSTは13～15か月と厳しいことから，再発を最小限にとどめる慎重な初回治療が肝要である．

●再発例の治療目標は延命および症状緩和である．しかし，約20％はレスキューされる症例があることを念頭に置いて個別化治療を行う．

●単発再発はまず手術を考慮する．手術では肉眼的完全切除が要求される．不完全切除では手術のベネフィットが得られない．

●放射線照射の既往のない腟壁限局再発や骨盤内再発に対しては放射線療法が適用されるが，後者の場合は化学療法の併用（CCRT）が適用されても良い．

●ファーストライン化学療法はTC療法が第一選択となりつつある．

●TAP療法のわが国での認容性を確認したほうが良い．

●セカンドライン化学療法は現時点では期待できない．

●再発体がんでも化学療法に際しては，TFIあるいはPFIの概念が当てはまり，それに基づいた治療を考えるのが良い．

●黄体ホルモン療法は類内膜腺がんG1あるいはPR陽性例に対し選択肢になるが，その効果は限定的である．

●分子標的薬のなかではmTOR阻害薬と抗VEGF阻害薬が注目されており，抗がん剤との併用の臨床試験の結果が期待される．

参考文献

1） 子宮体がん治療ガイドライン2009年版，日本婦人科腫瘍学会／編，金原出版，東京

2） Fung-Kee-Fung M, Dodge J, Elit L, et al : Follow-up after primary therapy for endometrial cancer : A systematic review. Gynecol Oncol 101 : 520─529, 2006

3） Sartori E, Laface B, Dadducci A, et al : Factors influencing survival in endometrial cancer relapsing patients : a Cooperation Task Force（CTF） study. Int J Gynecol Cancer 13 : 458─465, 2003

4） 長谷川清志，大江収子，鳥居　裕，他 : 子宮体癌再発症例に対する手術療法の意義．日婦腫瘍会誌28 : 409─417, 2010

5） Ozols RF, Bundy BN, Greer BE, et al : Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer : a Gynecologic Oncology Group study. J Clin Oncol 21 : 3194─3200, 2003

6） Creutzberg CL, van Putten WLJ, Koper PC, et al : Survival after relapse in patients with endometrial cancer : results from a randomized trial. Gynecol Oncol 89 : 201─209, 2003

7） Sohaib SA, Houghton SL, Meroni R, et al : Recurrent endometrial cancer : patterns of recurrent disease and assessment of prognosis. Clin Radiol 62 : 28─34, 2007

8） Bristow RE, Santillan A, Zahurak ML, et al : Salvage cytoreductive surgery for recurrent endometrial cancer. Gynecol Oncol 103 : 281─287, 2006

9） Odagiri T, Watari H, Hosaka M, et al : Multivariate survival analysis of the patients with recurrent endometrial cancer. J Gynecol Oncol 22 : 3─8, 2011

10） Morris M, Alvarez RD, Kinney WK, Wilson TO : Treatment of recurrent adenocarcinoma of the endometrium with pelvic exenteration. Gynecol Oncol 60 : 288─291, 1996

11） Barakat RR, Goldman NA, Patel DA, Venkatraman ES, Curtin JP : Pelvic exenteration for recurrent endometrial cancer. Gynecol Oncol 75 : 99─102, 1999

12） Baiocchi G, Guimaraes GC, Rosa Oliveira RA, et al : Prognostic factors in pelvic exenteration for gynecological malignancies. Eur J Surg Oncol 38 : 948─954, 2012

13） Kaur M, Joniau S, D’Hoore A, et al : Pelvic exenterations for gynecological malignancies : a study of 36 cases. Int J Gynecol Cancer 22 : 889─896, 2012

14） Scarabelli C, Campagnutta E, Giorda G, et al : Maximal cytoreductive surgery as a reasonable therapeutic alternative for recurrent endometrial carcinoma. Gynecol Oncol 70 : 90─93, 1998

15） Campagnutta E, Giorda G, Piero GD, et al : Surgical treatment of recurrent endometrial carcinoma. Cancer 100 : 89─96, 2005

16） Awtrey CS, Gadungog MG, Leitao MM, et al : Surgical resection of recurrent endometrial carcinoma. Gynecol Oncol 102 : 480─488, 2006

17） Nag S, Yacoub S, Copeland LJ, et al : Interstitial brachyth erapy for salvage treatment of vaginal recurrences in previously unirradiated endometrial cancer patients. Int J Radiat Oncol Biol Phys 54 : 1153─1159, 2002

18） Jhingran A, Burke TW, Eifel PJ : Definitive radiotherapy for patients with isolated vaginal recurrence of endometrial carcinoma after hysterectomy. Int J Radiat Oncol Biol Phys 56 : 1366─1372, 2003

19） Lin LL, Grigsby PW, Powell MA, Mutch DG : Definitive radiotherapy in the management of isolated vaginal recurrences of endometrial cancer. Int J Radiat Oncol Biol Phys 63 : 500─504, 2005

20） Petignat P, Jolicoeur M, Alobaid A, et al : Salvage treatment with high-dose-rate brachytherapy for isolated vaginal endometrial cancer recurrence. Gynecol Oncol 101 : 445─449, 2006

21） Huh WK, Straughn JM Jr, Mariani A, et al : Salvage of isolated vaginal recurrences in women with surgical stage I endometrial cancer : a multiinstitutional experience. Int J Gynecol Cancer 17 : 886─889, 2007

22） Sorbe B, Söderström K : Treatment of vaginal recurrences in endometrial carcinoma by high-dose-rate brachytherapy. Anticancer Res 33 : 241─247, 2013

23） Hoekstra CJ, Koper PC, van Putten WL : Recurrent endometrial adenocarcinoma after surgery alone : prognostic factors and treatment. Radiother Oncol 27 : 164─166, 1993

24） Ackerman I, Malone S, Thomas G, et al : Endometrial carcinoma--relative effectiveness of adjuvant irradiation vs therapy reserved for relapse. Gynecol Oncol 60 : 177─183, 1996

25） Hart KB, Han I, Shamsa F, et al : Radiation therapy for endometrial cancer in patients treated for postoperative recurrence. Int J Radiat Oncol Biol Phys 41 : 7─11, 1998

26） Jereczek-Fossa B, Badzio A, Jassem J : Recurrent endometrial cancer after surgery alone : results of salvage radiotherapy. Int J Radiat Oncol Biol Phys 48 : 405─413, 2000

27） Wylie J, Irwin C, Pintilie M, et al : Results of radical radiotherapy for recurrent endometrial cancer. Gynecol Oncol 77 : 66─72, 2000

28） Creutzberg CL, van Putten WL, Koper PC, et al : PORTEC Study Group. Survival after relapse in patients with endometrial cancer : results from a randomized trial. Gynecol Oncol 89 : 201─209, 2003

29） Thigpen JT, Blessing JA, DiSaia PJ, et al : A randomized comparison of doxorubicin alone versus doxorubicin plus cyclophosphamide in the management of advanced or recurrent endometrial carcinoma : A Gynecologic Oncology Group study. J Clin Oncol 12 : 1408─1414, 1994

30） Thigpen JT, Brady MF, Homesley HD, et al : Phase III study of doxorubicin with or without cisplatin in advanced or recurrent endometrial carcinoma. : a gynecologic oncology group study. J Clin Oncol 22 : 3902─3908, 2004

31） Aapro MS, Van Wijk FH, et al : Doxorubicin versus doxorubicin and cisplatin in endometrial carcinoma : definitive results of a randomized study（55872） by the EORTC Gynecological Cancer Group. Ann Oncol 14 : 441─448, 2003

32） Fleming GF, Filiaci VL, Bentley RC, et al : Phase III randomized trial of doxorubicin＋cisplatin versus doxorubicin+24-h paclitaxel+filgrastim in endometrial carcinoma : a Gynecologic Oncology Group study. Ann Oncol 15 : 1173─1178, 2004

33） Fleming GF, Brunetto VL, Cella D, et al : Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advancedendometrial carcinoma : a Gynecologic Oncology Group Study. J Clin Oncol 22 : 2159─2166, 2004

34） Nomura H, Aoki D, Takahashi F, et al : Randomized phase II study comparing docetaxel plus cisplatin, docetaxel plus carboplatin, and paclitaxel plus carboplatin in patients with advanced or recurrent endometrial carcinoma : a Japanese Gynecologic Oncology Group study（JGOG2041）. Ann Oncol 22 : 636─642, 2011

35） Makker V, Hensley ML, Zhou Q, et al : Treatment of advanced or recurrent endometrial carcinoma with doxorubicin in patients progressing after paclitaxel/carboplatin : Memorial Sloan-Kettering Cancer Center experience from 1995 to 2009. Int J Gynecol Cancer 23 : 929─934, 2013

36） Sutton GP, Blessing JA, Homesley HD, et al : Phase II study of ifosfamide and mesna in refractory adenocarcinoma of the endometrium. A Gynecologic Oncology Group study. Cancer 73 : 1453─1455, 1994

37） Miller DS, Blessing JA, Lentz SS, Waggoner SE : A phase II trial of topotecan in patients with advanced, persistent, or recurrent endometrial carcinoma : a gynecologic oncology group study. Gynecol Oncol 87 : 247─251, 2002

38） Muggia FM, Blessing JA, Sorosky J, Reid GC : Phase II trial of the pegylated liposomal doxorubicin in previously treated metastatic endometrial cancer : a Gynecologic Oncology Group study. J Clin Oncol 20 : 2360─2364, 2002

39） Lincoln S, Blessing JA, Lee RB, Rocereto TF : Activity of paclitaxel as second-line chemotherapy in endometrial carcinoma : a Gynecologic Oncology Group study. Gynecol Oncol 88 : 277─281, 2003

40） Fracasso PM, Blessing JA, Molpus KL, Adler LM, Sorosky JI, Rose PG : Phase II study of oxaliplatin as second-line chemotherapy in endometrial carcinoma : a Gynecologic Oncology Group study. Gynecol Oncol 103 : 523─526, 2006

41） Garcia AA, Blessing JA, Nolte S, Mannel RS : Gynecologic Oncology Group A phase II evaluation of weekly docetaxel in the treatment of recurrent or persistent endometrial carcinoma : a study by the Gynecologic Oncology Group. Gynecol Oncol 111 : 22─26, 2008

42） Miller DS, Blessing JA, Drake RD, et al : A phase II evaluation of pemetrexed （Alimta, LY231514, IND＃40061） in the treatment of recurrent or persistent endometrial carcinoma : a phase II study of the Gynecologic Oncology. Gynecol Oncol 115 : 443─446, 2009

43） Dizon DS, Blessing JA, McMeekin DS, et al : Phase II trial of ixabepilone as second-line treatment in advanced endometrial cancer : gynecologic oncology group trial 129-P. J Clin Oncol 27 : 3104─3108, 2009

44） Tait DL, Blessing JA, et al : A phase II study of gemcitabine （gemzar, LY188011） in the treatment of recurrent or persistent endometrialcarcinoma : a gynecologic oncology group study. Gynecol Oncol 121 : 118─121, 2011

45） Pignata S, Scambia G, Pisano C, et al : A multicentre phase II study of carboplatin plus pegylated liposomal doxorubicin as first-line chemotherapy for patients with advanced or recurrent endometrial carcinoma : the END-1 study of the MITO（Multicentre Italian Trials in Ovarian Cancer and Gynecologic Malignancies） group. Br J Cancer 96 : 1639─1643, 2007

46） Mazgani M, Le N, Hoskins PJ : British Columbia Cancer Agency. Reuse of carboplatin and paclitaxel in patients with relapsed endometrial cancer--the British Columbia Cancer Agency experience. Gynecol Oncol 111 : 474─477, 2008

47） Ueda Y, Miyake T, Egawa-Takata T, et al : Second-line chemotherapy for advanced or recurrent endometrial carcinoma previously treated with paclitaxel and carboplatin, with or without epirubicin. Cancer Chemother Pharmacol 67 : 829─835, 2011

48） Miyake T, Ueda Y, Egawa-Takata T, et al : Recurrent endometrial carcinoma : prognosis for patients with recurrence within 6 to 12 months is worse relative to those relapsing at 12 months or later. Am J Obstet Gynecol 204 : 535. e1─5, 2011

49） Nagao S, Nishio S, Michimae H, et al : Applicability of the concept of “platinum sensitivity” to recurrent endometrial cancer : The SGSG-012/GOTIC-004/Intergroup study. Gynecol Oncol, 2013（In Press）

50） Thigpen JT, Brady MF, Alvarez RD, et al : Oral medroxyprogesterone acetate in the treatment of advanced or recurrent endometrial carcinoma : a dose-response study by the Gynecologic Oncology Group. J Clin Oncol 17 : 1736─1744, 1999

51） Lentz SS, Brady MF, Major FJ, Reid GC, Soper JT : High-dose megestrol acetate in advanced or recurrent endometrial carcinoma : a Gynecologic Oncology Group Study. J Clin Oncol 14 : 357─361, 1996

52） Thigpen T, Brady MF, Homesley HD, Soper JT, Bell J : Tamoxifen in the treatment of advanced or recurrent endometrial carcinoma : a Gynecologic Oncology Group study. J Clin Oncol 19 : 364─367, 2001

53） Whitney CW, Brunetto VL, Zaino RJ, et al : Phase II study of medroxyprogesterone acetate plus tamoxifen in advanced endometrial carcinoma : a Gynecologic Oncology Group study. Gynecol Oncol 92 : 4─9, 2004

54） Fiorica JV, Brunetto VL, Hanjani P, et al : Phase II trial of alternating courses of megestrol acetate and tamoxifen in advanced endometrial carcinoma : a Gynecologic Oncology Group study. Gynecol Oncol 92 : 10─14, 2004

55） Rose PG, Brunetto VL, VanLe L, et al : A phase II trial of anastrozole in advanced recurrent or persistent endometrial carcinoma : a Gynecologic Oncology Group study. Gynecol Oncol 78 : 212─216, 2000

56） Oza AM, Elit L, Tsao MS, et al : Phase II study of temsirolimus in women with recurrent or metastatic endometrial cancer : a trial of the NCIC Clinical Trials Group. J Clin Oncol 29 : 3278─3285, 2011

57） Colombo N, McMeekin DS, Schwartz PE, et al : Ridaforolimus as a single agent in advanced endometrial cancer : results of a single-arm, phase 2 trial. Br J Cancer 108 : 1021─1026, 2013

58） Slomovitz BM, Lu KH, Johnston T, et al : A phase 2 study of the oral mammalian target of rapamycin inhibitor, everolimus, in patients with recurrent endometrial carcinoma. Cancer 116 : 5415─5419, 2010

59） Oza AM, Eisenhauer EA, Elit L, et al : Phase II study of erlotinib in recurrent or metastatic endometrial cancer : NCIC IND-148. J Clin Oncol 26 : 4319─4325, 2008

60） Leslie KK, Sill MW, Fischer E, et al : A phase II evaluation of gefitinib in the treatment of persistent or recurrent endometrial cancer : a Gynecologic Oncology Group study. Gynecol Oncol 129 : 486─494, 2013

61） Aghajanian C, Sill MW, Darcy KM, et al : Phase II trial of bevacizumab in recurrent or persistent endometrial cancer : a Gynecologic Oncology Group study. J Clin Oncol 29 : 2259─2265, 2011

62） Fleming GF, Morgan R, Wang L, et al : A phase II study of sunitinib in recurrent or metastatic endometrial carcinoma : a trial of the PMH Phase II consortium. J Clin Oncol 2010 ; 28（suppl）, abstract number 5038

63） Alvarez EA, Brady WE, Walker JL, et al : Phase II trial of combination bevacizumab and temsirolimus in the treatment of recurrent or persistent endometrial carcinoma : a Gynecologic Oncology Group study. Gynecol Oncol 129 : 22─27, 2013