Poly ADP-ribose polymerase inhibitor (PARPi) is the breakthrough drug for ovarian cancer over the past decade. PARPi is used for the maintenance treatment of ovarian cancer by blocking enzymes involved in the DNA repair process. However, PARPi-induced thrombocytopenia not only increases the risk of bleeding in patients, reduces the dose of therapeutic drugs, delays the duration of medication, but also leads to the termination of treatment in severe cases, and great attention should be paid to PARPi-induced thrombocytopenia. This paper focuses on the incidence, mechanisms, risk factors, prevention and treatment methods for PARPi-induced thrombocytopenia, as to provide references for clinical prevention and treatment of PARPi-induced thrombocytopenia.

1.曹毛毛, 陈万青. GLOBOCAN 2020全球癌症统计数据解读[J]. 中国医学前沿杂志: 电子版, 2021, 13(3): 63-69. [Cao MM, Chen WQ. Interpretation on the global cancer statistics of GLOBOCAN 2020[J]. Chinese Journal of the Frontiers of Medical Science (Electronic Version), 2021, 13(3): 63-69.] DOI: 10.12037/YXQY.2021.03-10.

2.孔北华, 刘继红, 黄鹤,等. 卵巢癌PARP抑制剂临床应用指南（2022版）[J]. 现代妇产科进展, 2022, 31(8): 561-572. [Kong BH, Liu JH, Huang H, et al. A clinical guide to using PARP inhibitors in overian cancer[J]. Progress in Obstetrics and Gynecology, 2022, 31(8): 561-572.] DOI: 10.13283/j.cnki.xdfckjz.2022.08.001.

3.Makin S. What's next for PARP inhibitors?[J]. Nature, 2021, 600(7889)：S36-S38. DOI: 10.1038/D41586-021-03714-W.

4.Pujade-Lauraine E, Ledermann JA, Selle F, et al. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial[J]. Lancet Oncol, 2021, 22(5): 620-631. DOI: 10.1016/S1470-2045(21)00073-5.

5.Moore K, Colombo N, Scambia G, et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer[J]. N Engl J Med, 2018, 379(26): 2495-2505. DOI: 10.1056/NEJMoa1810858.

6.Gao QL, Zhu JQ, Zhao WD, et al. Olaparib maintenance monotherapy in Asian patients with platinum-sensitive relapsed ovarian cancer: phase III trial (L-MOCA)[J]. Clin Cancer Res, 2022, 28(11): 2278-2285. DOI: 10.1158/1078-0432.CCR-21-3023.

7.Ray-Coquard I, Pautier P, Pignata S, et al. Olaparib plus bevacizumab as first-line maintenance in ovarian cancer[J]. N Engl J Med, 2019, 381(25): 2416-2428. DOI: 10.1056/NEJMoa1911361.

8.Ledermann JA, Oza AM, Lorusso D, et al. Rucaparib for patients with platinum-sensitive, recurrent ovarian carcinoma (ARIEL3): post-progression outcomes and updated safety results from a randomised, placebo-controlled, phase 3 trial[J]. Lancet Oncol, 2020, 21(5): 710-722. DOI: 10.1016/S1470-2045(20)30061-9.

9.Mirza MR, Monk BJ, Herrstedt J, et al. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer[J]. N Engl J Med, 2016, 375(22): 2154-2164. DOI: 10.1056/NEJMoa1611310.

10.Li N, Zhang YZ, Wang J, et al. Fuzuloparib maintenance therapy in patients with platinum-sensitive, recurrent ovarian carcinoma (FZOCUS-2): a multicenter, randomized, double-blind, placebo-controlled, phase III trial[J]. J Clin Oncol, 2022, 40(22): 2436-2446. DOI: 10.1200/JCO.21.01511.

11.Wu X, Zhu J, Wang J, et al. Pamiparib monotherapy for patients with germline BRCA1/2-mutated ovarian cancer previously treated with at least two lines of chemotherapy: a multicenter, open-label, phase II study[J]. Clin Cancer Res, 2022, 28(4): 653-661. DOI: 10.1158/1078-0432.CCR-21-1186.

12.Luo X, Kraus WL. On PAR with PARP: cellular stress signaling through poly (ADP-ribose) and PARP-1[J]. Genes Dev, 2012, 26(5): 417-432. DOI: 10.1101/gad. 183509.111.

13.Lord CJ, Ashworth A. PARP inhibitors: synthetic lethality in the clinic[J]. Science, 2017, 355(6330): 1152-1158. DOI: 10.1126/science.aam7344.

14.Bai P. Biology of poly(ADP-Ribose) polymerases: the factotums of cell maintenance[J]. Molecular Cell, 2015, 58(6): 947-958. DOI: 10.1016/j.molcel.2015.01.034.

15.Wang S, Guo M, Zhang X, et al. PARP inhibitor-related haemorrhages: what does the real-world study say?[J]. Front Oncol, 2023, 13: 1070343. DOI: 10.3389/fonc.2023.1070343.

16.Hopkins TA, Ainsworth WB, Ellis PA, et al. PARP1 trapping by PARP inhibitors drives cytotoxicity in both cancer cells and healthy bone marrow[J]. Mol Cancer Res, 2019, 17(2): 409-419. DOI: 10.1158/1541-7786.MCR-18-0138.

17.冯征, 吴小华. PARP抑制剂用于铂敏感复发卵巢癌患者维持治疗的血液学毒性概述[J]. 中国癌症杂志, 2020, 30(4): 299-304. [Feng Z, Wu XH. Hematological toxicities of maintenance PARP inhibitors for patients with platinum-sensitive recurrent ovarian cancer[J]. China Oncology, 2020, 30(4): 299-304.] DOI: 10.19401/j.cnki.1007-3639.2020.04.009.

18.Mateo J, Moreno V, Gupta A, et al. An adaptive study to determine the optimal dose of the tablet formulation of the PARP inhibitor olaparib[J]. Target Oncol, 2016, 11(3): 401-415. DOI: 10.1007/s11523-016-0435-8.

19.Kristeleit R, Shapiro GI, Burris HA, et al. A phase I-II study of the oral PARP inhibitor rucaparib in patients with germline BRCA1/2-mutated ovarian carcinoma or other solid tumors[J]. Clin Cancer Res, 2017, 23(15): 4095-4106. DOI: 10.1158/1078-0432.CCR-16-2796.

20.Li H, Liu R, Shao B, et al. Phase I dose-escalation and expansion study of PARP inhibitor, fluzoparib (SHR3162), in patients with advanced solid tumors[J]. Chin J Cancer Res, 2020, 32(3): 370-382. DOI: 10.21147/j.issn.1000-9604.2020.03.08.

21.Xu B, Yin Y, Dong M, et al. Pamiparib dose escalation in Chinese patients with non-mucinous high-grade ovarian cancer or advanced triple-negative breast cancer[J]. Cancer Med, 2021, 10(1): 109-118. DOI: 10.1002/cam4. 3575.

22.Sandhu SK, Schelman WR, Wilding G, et al. The poly(ADP-ribose) polymerase inhibitor niraparib (MK4827) in BRCA mutation carriers and patients with sporadic cancer: a phase 1 dose-escalation trial[J]. Lancet Oncol, 2013, 14(9): 882-892. DOI: 10.1016/S1470-2045(13)70240-7.

23.中国药师协会肿瘤专科药师分会, 中国抗癌协会肿瘤临床药学专业委员会, 浙江省抗癌协会肿瘤临床药学专业委员会, 等. 聚腺苷二磷酸核糖聚合酶抑制剂药物相互作用管理中国专家共识（2023版）[J]. 中华肿瘤杂志, 2023, 45(7): 585-594. DOI: 10.3760/cma.j.cn112152-20221223-00849.

24.Wang C, Li J. Haematologic toxicities with PARP inhibitors in cancer patients: an up-to-date meta-analysis of 29 randomized controlled trials[J]. J Clin Pharm Ther, 2021, 46(3): 571-584. DOI: 10.1111/jcpt.13349.

25.Zhou JX, Feng LJ, Zhang X. Risk of severe hematologic toxicities in cancer patients treated with PARP inhibitors: a meta-analysis of randomized controlled trials[J]. Drug Des Devel Ther, 2017, 11: 3009-3017. DOI: 10.2147/DDDT.S147726.

26.Berek JS, Matulonis UA, Peen U, et al. Safety and dose modification for patients receiving niraparib[J]. Ann Oncol, 2018, 29(8): 1784-1792. DOI: 10.1093/annonc/mdy181.

27.Konecny GE, Oza AM, Tinker AV, et al. Population exposure-efficacy and exposure-safety analyses for rucaparib in patients with recurrent ovarian carcinoma from Study 10 and ARIEL2[J]. Gynecol Oncol, 2021, 161: 668-675. DOI: 10.1016/j.ygyno.2021.03.015.

28.Smith JA, Le T, Martin GA, et al. Identifying the need to refine the potential patient risk factors for niraparib-induced thrombocytopenia[J]. Gynecol Oncol, 2019, 152(2): 265-269. DOI: 10.1016/j.ygyno.2018.11.024.

29.Green ML, Ma SC, Goble S, et al. Population pharmacokinetics of rucaparib in patients with advanced ovarian cancer or other solid tumors[J]. Cancer Chemother Pharmacol, 2022, 89: 671-682. DOI: 10.1007/s00280-022-04413-7.

30.Grechko N, Skarbova V, Tomaszewska-Kiecana M, et al. Pharmacokinetics and safety of rucaparib in patients with advanced solid tumors and hepatic impairment[J]. Cancer Chemother Pharmacol, 2021, 88: 259-270. DOI: 10.1007/s00280-021-04278-2.

31.中国临床肿瘤学会指南工作委员会, 编著. 中国临床肿瘤学会（CSCO）卵巢癌诊疗指南-2022[M]. 北京:人民卫生出版社, 2022.

32.中国抗癌协会妇科肿瘤专业委员会. PARP抑制剂不良反应管理的中国专家共识（2021年版）[J]. 中国实用妇科与产科杂志, 2021, 37(11): 1119-1130. DOI: 10.19538/j.fk2021110111.

33.Kuter DJ. The structure, function, and clinical use of the thrombopoietin receptor agonist avatrombopag[J]. Blood Rev, 2022, 53: 100909. DOI: 10.1016/j.blre.2021.100909.

34.Yan D, Yang J, Gao YF, et al. Combination of thrombopoietin receptor agonist and recombinant human thrombopoietin for treating cancer therapy induced thrombopenia[J]. Blood, 2022, 140(S1): 1. DOI: 10.1182/BLOOD-2022-164490.

35.方静, 张荣艳, 肖承京. 白细胞介素11的细胞生物学作用及防治疾病的研究进展[J]. 实用临床医学, 2005, 6(8): 150-152. [Fang J, Zhang RY, Xiao CJ. Research progress on the cellular biological effects of interleukin-11 and its prevention and treatment of diseases[J]. Practical Clinical Medicine, 2005, 6(8): 150-152.] DOI: 10.3969/j.issn.1009-8194.2005.08.089.

36.中国临床肿瘤学会抗淋巴瘤联盟, 中国临床肿瘤学会抗白血病联盟, 中国临床肿瘤学会抗肿瘤药物安全管理专家委员会, 等. 重组人白介素-11防治血小板减少症临床应用中国专家共识（2021年版）[J]. 临床肿瘤学杂志, 2020, 25(12): 1129-1137. DOI: 10.3969/j.issn. 1009-0460.2020.12.014.

37.Soff GA, Miao Y, Bendheim G, et al. Romiplostim treatment of chemotherapy-induced thrombocytopenia[J]. J Clin Oncol, 2019, 37(31): 2892-2898. DOI: 10.1200/JCO. 18.01931.

38.National Comprehensive Cancer Network. NCCN Practice Guidelines in Oncology: Hematopoietic growth factors (2023.v1)[EB/OL]. (2023) [2023-09-06]. https:www.nccr.org/professional/physician_gls/pdf/growthfactors.pdf.

39.Winer ES, Safran H, Karaszewska B, et al. Eltrombopag for thrombocytopenia in patients with advanced solid tumors receiving gemcitabine-based chemotherapy: a randomized, placebo-controlled phase 2 study[J]. Int J Hematol, 2017, 106(6): 765-776. DOI: 10.1007/s12185-017-2319-9.

40.Kellum A, Jagiello-Gruszfeld A, Bondarenko IN, et al. A randomized, double-blind, placebo-controlled, dose ranging study to assess the efficacy and safety of eltrombopag in patients receiving carboplatin/paclitaxel for advanced solid tumors[J]. Curr Med Res Opin, 2010, 26(10): 2339-2346. DOI: 10.1185/03007995.2010. 510051.

41.Winer ES, Safran H, Karaszewska B, et al. Eltrombopag with gemcitabine-based chemotherapy in patients with advanced solid tumors: a randomized phase I study[J]. Cancer Med, 2015, 4(1): 16-26. DOI: 10.1002/cam4.326.

42.Al-Samkari H, Kolb-Sielecki J, Safina SZ, et al. Avatrombopag for chemotherapy-induced thrombocytopenia in patients with non-haematological malignancies: an international, randomised, double-blind, placebo-controlled, phase 3 trial[J]. Lancet Haematol, 2022, 9(3): e179-e189. DOI: 10.1016/S2352-3026(22) 00001-1.