臨床婦人科産科71巻10号

2017年10月発行

今月の臨床 最新！　婦人科がん薬物療法─化学療法薬から分子標的薬・免疫療法薬まで 子宮頸がん

子宮頸がん治療に対する最新化学療法─ベバシズマブの位置づけとその副作用対策

著者： 馬淵誠士¹ 甲村奈緒子¹ 松本有里¹

所属機関： ¹大阪大学大学院医学系研究科産科学婦人科学講座

ページ範囲：P.948 - P.959

●進行・再発子宮頸がんに対する化学療法は，殺細胞性抗がん剤の2剤併用から，殺細胞性抗がん剤2剤＋分子標的治療薬へと変化しつつある．

●ベバシズマブの有効性が証明され，保険診療下のベバシズマブ併用が可能となった現在も，化学療法の位置づけは，あくまで「延命およびQOLの改善」である．

●重篤な有害事象（血栓塞栓症・消化管穿孔・瘻孔）が報告されているため，ベバシズマブの使用を考慮する際には，慎重な症例選択と十分なインフォームド・コンセントが必要である．

参考文献

1）馬淵誠士，他 : 子宮頸がんの化学療法と分子標的治療．産と婦1 : 31─37, 2016

2）Ojesina AI, et al : Landscape of genomic alterations in cervical carcinomas. Nature 506 : 371─375, 2014

3）Monk BJ, et al : Phase II, open-label study of pazopanib or lapatinib monotherapy compared with pazopanib plus lapatinib combination therapy in patients with advanced and recurrent cervical cancer. J Clin Oncol 28 : 3562─3569, 2010

4）Mackay HJ, et al : A phase II study of sunitinib in patients with locally advanced or metastatic cervical carcinoma : NCIC CTG Trial IND.184. Gynecol Oncol 116 : 163─167, 2010

5）Symonds RP, et al : Cediranib combined with carboplatin and paclitaxel in patients with metastatic or recurrent cervical cancer（CIRCCa） : a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Oncol 16 : 1515─1524, 2015

6）Kunos C, et al : A phase I-II evaluation of veliparib（NSC＃737664）, topotecan, and filgrastim or pegfilgrastim in the treatment of persistent or recurrent carcinoma of the uterine cervix : an NRG Oncology/Gynecologic Oncology Group study. Int J Gynecol Cancer 25 : 484─492, 2015

7）Cetina L, et al : A pilot study of nimotuzumab plus single agent chemotherapy as second- or third-line treatment or more in patients with recurrent, persistent or metastatic cervical cancer. Cancer Biol Ther 16 : 684─689, 2015

8）Santin AD, et al : Phase II trial of cetuximab in the treatment of persistent or recurrent squamous or non-squamous cell carcinoma of the cervix : a Gynecologic Oncology Group study. Gynecol Oncol 122 : 495─500, 2011

9）Farley J, et al : Phase II study of cisplatin plus cetuximab in advanced, recurrent, and previously treated cancers of the cervix and evaluation of epidermal growth factor receptor immunohistochemical expression : a Gynecologic Oncology Group study. Gynecol Oncol 121 : 303─308, 2011

10）Schilder RJ, et al : A phase II trial of erlotinib in recurrent squamous cell carcinoma of the cervix : a Gynecologic Oncology Group Study. Int J Gynecol Cancer 19 : 929─933, 2009

11）Nogueira-Rodrigues A, et al : Phase 2 trial of erlotinib combined with cisplatin and radiotherapy in patients with locally advanced cervical cancer. Cancer 120 : 1187─1193, 2014

12）Tinker AV, et al : Phase II study of temsirolimus（CCI-779） in women with recurrent, unresectable, locally advanced or metastatic carcinoma of the cervix. A trial of the NCIC Clinical Trials Group（NCIC CTG IND 199）. Gynecol Oncol 130 : 269─274, 2013

13）Frenel JS, et al : Pembrolizumab in Patients with Advanced Cervical Cancer : Preliminary Results from the Phase Ib KEYNOTE-028 Study. ASCO 2016 : abstract＃5515, 2016

14）Lopez-Ocejo O, et al : Oncogenes and tumor angiogenesis : the HPV-16 E6 oncoprotein activates the vascular endothelial growth factor（VEGF） gene promoter in a p53 independent manner. Oncogene 19 : 4611─4620, 2000

15）Loncaster JA, et al : Vascular endothelial growth factor（VEGF）expression is a prognostic factor for radiotherapy outcome in advanced carcinoma of the cervix. Br J Cancer 83 : 620─625, 2000

16）Monk BJ, et al : Phase II trial of bevacizumab in the treatment of persistent or recurrent squamous cell carcinoma of the cervix : a gynecologic oncology group study. J Clin Oncol 27 : 1069─1074, 2009

17）Zighelboim I, et al : Multicenter phase II trial of topotecan, cisplatin and bevacizumab for recurrent or persistent cervical cancer. Gynecol Oncol 130 : 64─68, 2013

18）Tewari KS, et al : Improved survival with bevacizumab in advanced cervical cancer. N Eng J Med 370 : 734─743, 2014

19）Penson RT : Bevacizumab for advanced cervical cancer : patient-reported outcomes of a randomised, phase 3 trial（NRG Oncology-Gynecologic Oncology Group protocol 240）. Lancet Oncol 16 : 301─311, 2015

20）Tewari KS, et al : Prospective validation of pooled prognostic factors in women with advanced cervical cancer treated with chemotherapy with/without bevacizumab : NRG Oncology/GOG Study. Clin Cancer Res 21 : 5480─5487, 2015

21）医薬品医療機器総合機構 : 審議結果報告書．2016　http://www.pmda.go.jp/drugs/2016/P20160518003/450045000_21900AMX00910_A100_1.pdf

22）結腸・直腸癌に対する国内特定使用成績調査

23）Wu S, et al : Incidence and risk of hypertension with sorafenib in patients with cancer : a systematic review and meta-analysis. Lancet Oncol 9 : 117, 2008

24）Lafayette RA, et al : Incidence and relevance of proteinuria in bevacizumab-treated patients : pooled analysis from randomized controlled trials. Am J Nephrol 40 : 75─83, 2014

25）Scappaticci FA, et al : Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab. J Natl Cancer Inst 99 : 1232─1239, 2007

26）Hapani S, et al : Risk of gastrointestinal perforation in patients with cancer treated with bevacizumab : a meta-analysis. Lancet Oncol 10 : 559─568, 2009

27）Burger RA, et al : Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med 365 : 2473─2483, 2011

28）Kozloff M, et al : Clinical outcomes associated with bevacizumab-containing treatment of metastatic colorectal cancer : the BRiTE observational cohort study. Oncologist 14 : 862─870, 2009

29）Kabbinavar FF, et al : Gastrointestinal perforation associated with bevacizumab use in metastatic colorectal cancer : results from a large treatment observational cohort study. Eur J Cancer 48 : 1126─1132, 2012

30）Saif MW, et al : Gastrointestinal perforation due to bevacizumab in colorectal cancer. Ann Surg Oncol 14 : 1860─1869, 2007

31）Burger RA, et al : Risk factors for GI adverse events in a phase III randomized trial of bevacizumab in first-line therapy of advanced ovarian cancer : A Gynecologic Oncology Group Study. J Clin Oncol 32 : 1210─1217, 2014

32）Tanyi JL, et al : Clinical predictors of bevacizumab-associated gastrointestinal perforation. Gynecol Oncol 120 : 464─469, 2011

33）Perren TJ, et al : A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med 365 : 2484─2496, 2011

34）Schefter T, et al : RTOG 0417 : efficacy of bevacizumab in combination with definitive radiation therapy and cisplatin chemotherapy in untreated patients with locally advanced cervical carcinoma. Int J Radiat Oncol Biol Phys 88 : 101─110, 2014