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Effect of neoadjuvant chemotherapy combined with intraperitoneal chemotherapy after interval tumor cell reduction on the prognosis of advanced epithelial ovarian cancer

  • Wei Wang1,†
  • Min Gao1,†
  • Xiaoting Li2
  • Hong Zheng1
  • Yunong Gao1,*,

1Department of Gynecologic Oncology, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, 100142 Beijing, China

2Department of Radiology, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, 100142 Beijing, China

DOI: 10.31083/j.ejgo4302030 Vol.43,Issue 2,April 2022 pp.238-246

Submitted: 09 November 2021 Accepted: 30 November 2021

Published: 15 April 2022

*Corresponding Author(s): Yunong Gao E-mail: gaoyunong@vip.sina.com

† These authors contributed equally.

Abstract

Objectives: To investigate the effect of neoadjuvant chemotherapy combined with intraperitoneal chemotherapy after interval tumor cell reduction on the prognosis of advanced epithelial ovarian cancer. Methods: A retrospective study was performed among 210 patients with advanced ovarian cancer who were treated with neoadjuvant chemotherapy from May 1, 2007 to December 1, 2015. 121 patients with NACT-IDS (Neoadjuvant chemotherapy followed by interval debulking surgery) were enrolled. The patients were divided into observation group (NACT-IDS + IP group, n = 28) and control group (NACT-IDS + IV group, n = 93) depending on whether intraperitoneal chemotherapy was used after interval debulking surgery. The effects of intraperitoneal chemotherapy after NACT-IDS on PFS (progression-free survival) and OS (overall survival) were analyzed and the influencing factors were explored through multivariate analysis. The competitive model was used to analyze the effect of intraperitoneal chemotherapy after NACT-IDS on tumor recurrence. Toxicities associated with adjuvant chemotherapy were also analyzed between two groups. The effect of neoadjuvant chemotherapy cycles on prognosis and the correlation between postoperative CA125 decline and recurrence were evaluated. Results: Intraperitonal chemotherapy and R0 (no gross residual) were independent factors for PFS, with HRs of 0.560 (95% CI, 0.342–0.918, p = 0.022) and 0.578 (95% CI, 0.377–0.887, p = 0.012). There was no independent factor associated with OS. Significant difference in PFS was detected among the R0 + IP group, R0 + IV group, non-R0 + IP group and non-R0 + IV group. In patients with R0 tumor reduction, IP patients showed significantly better PFS, bonferronei adjusted p = 0.036. In patients without R0 tumor reduction, no significant difference was detected between IP and IV group, bonferronei adjusted p = 0.28. There were no significant differences of grade 3–4 toxicities, abdominal pain, treatment delays, dose reductions, and treatment modifications in NACT-IDS + IP group and NACT-IDS + IV group. Neoadjuvant chemotherapy cycles (3 and >3) were not the influencing factors of PFS or OS and did not affect platinum-sensitive relapse or platinum-resistant relapse. The decrease in postoperative CA125 was not related to platinum-sensitive recurrence or platinum-resistant recurrence. Conclusions: Neoadjuvant chemotherapy combined with intraperitoneal chemotherapy after interval debulking surgery could improve the PFS of patients with advanced epithelial ovarian cancer compared to intravenous chemotherapy without significant differences in toxicity.


Keywords

Interval debulking surgery; Neoadjuvant chemotherapy; Intraperitoneal chemotherapy; Ovarian neoplasms

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Wei Wang,Min Gao,Xiaoting Li,Hong Zheng,Yunong Gao. Effect of neoadjuvant chemotherapy combined with intraperitoneal chemotherapy after interval tumor cell reduction on the prognosis of advanced epithelial ovarian cancer. European Journal of Gynaecological Oncology. 2022. 43(2);238-246.

References

[1] Robert FO , Brian NB, Benjamin EG, Jeffrey MF, Daniel CP, Robert AB, 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. Journal of Clinical Oncology. 2003; 21: 3194–3200.

[2] Rebecca LS , Kimberly DM, Ahmedin J. Cancer Statistics. CA: A Cancer Journal for Clinicians. 2017; 67: 7–30.

[3] Francesca R, Laura B , Roberta A , Rosaria C , Martina V , Stefano I , et al. Overcoming platinum-acquired resistance in ovarian cancer patient-derived xenografts. Therapeutic Advances in Medical Oncology. 2019; 11: 1758835919839543.

[4] Ignace V, Claes GT, Frédéric A, Gunnar BK, Tom E, Nick J, et al. Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. The New England Journal of Medicine. 2010; 363: 943–953.

[5] Shin N, Kimio U. Clinical significance of primary debulking surgery and neoadjuvant chemotherapy-interval debulking surgery in advanced ovarian cancer. Japanese Journal of Clinical Oncology. 2020; 50: 379–386.

[6] Takashi O, Toyomi S, Toshiaki S, Takahiro K, Toru N, Kenichi N, et al. Comparison of treatment invasiveness between upfront debulking surgery versus interval debulking surgery following neoadjuvant chemotherapy for stage III/IV ovarian, tubal, and peritoneal cancers in a phase III randomised trial: Japan Clinical Oncology Group Study JCOG0602. European Journal of Cancer. 2016; 64: 22–31.

[7] Suidan RS, Ramirez PT, Sarasohn DM, Teitcher JB, Iyer RB,MA QZ, et al. A multicenter assessment of the ability of preoperative computed tomography scan and CA 125 to predict gross residual disease at primary debulking for advanced epithelial ovarian cancer. Gynecologic Oncology. 2017; 145: 27–31.

[8] Dedrick RL, Myers CE, Bungay PM, DeVita Jr VT. Pharmacokinetic rationale for peritoneal drug administration in the treatment of ovarian cancer. Cancer Treatment Reports. 1978; 62: 1–11.

[9] Dedrick RL. Theoretical and experimental bases of intraperitoneal chemotherapy. Seminars in Oncology. 1985 Sep; 12: 1–6.

[10] Kenneth J , Nick J, Theresa AL. Intraperitoneal chemotherapy for the initial management of primary epithelial ovarian cancer. The Cochrane Database of Systematic Reviews. 2016; 2016: CD005340.

[11] Lopez JA, Krikorian JG, Reich SD, Smyth RD, Lee FH, Issell BF. Clinical pharmacology of intraperitoneal cisplatin. Gynecologic Oncology. 1985; 20: 1–9.

[12] Francis P, Rowinsky E, Schneider J, Hakes T, Hoskins W, Markman M. Phase I feasibility and pharmacologic study of weekly intraperitoneal paclitaxel: a Gynecologic Oncology Group pilot Study. Journal of Clinical Oncology. 1995; 13: 2961–2967.

[13] Joan LW , Deborah KA, Helen QH, Jeffrey F, Kenneth W, Robert AB, et al. Intraperitoneal catheter outcomes in a phase III trial of intravenous versus intraperitoneal chemotherapy in optimal stage III ovarian and primary peritoneal cancer: A Gynecologic Oncology Group study. Gynecologic Oncology. 2006; 100: 27–32.

[14] Joan L W, Mark FB, Lari W, Gini FF, Helen QH, Paul AD, et al. Randomized Trial of Intravenous Versus Intraperitoneal Chemotherapy Plus Bevacizumab in Advanced Ovarian Carcinoma: An NRG Oncology/Gynecologic Oncology Group Study. Journal of Clinical Oncology. 2019; 37: 1380–1390.

[15] Vermorken JB. The role of intraperitoneal chemotherapy in epithelial ovarian cancer. International Journal of Gynecological Cancer. 2000; 10: 26–32.

[16] Laurie E, Thomas KO, Allan C, Janice K, Michael FKF, Holger WH, et al. Intraperitoneal chemotherapy in the first-line treatment of women with stage III epithelial ovarian cancer: a systematic review with metaanalyses. Cancer. 2007; 109: 692–702.

[17] Rebecca S, Amy H, Bryn R, Richard JE. Decision-Making in Gynaecological Oncology Multidisciplinary Team Meetings: A Cross-Sectional, Observational Study of Ovarian Cancer Cases. Oncology Research and Treatment. 2020; 43: 70–77.

[18] Markman M. Intraperitoneal antineoplastic agents for tumors principally confined to the peritoneal cavity. Cancer Treatment Reviews. 1986; 13: 219–242.

[19] Huinink W W TB, Dubbelman R, Aartsen E, Franklin H, McVie JG. Experimental and clinical results with intraperitoneal cisplatin. Seminars in Oncology. 1985; 12: 43–46.

[20] Devansu T, James JJ, Ritu S, Deborah KA, Maurie M, Thomas H, et al. Long-term survival advantage and prognostic factors associated with intraperitoneal chemotherapy treatment in advanced ovarian cancer: a Gynecologic Oncology Group Study. Journal of Clinical Oncology. 2015; 33: 1460–1466.

[21] Ignace V, Frederic A, Karin L, Isabelle C, Toon VG, Patrick N, et al. Intraperitoneal chemotherapy in patients with advanced ovarian cancer: the con view. Oncologist. 2008; 13: 410–414.

[22] Deborah KA, Ronald DA, Jamie NBG, Lisa B, Kian B, Andrew B, et al. NCCN Guidelines Insights: Ovarian Cancer, Version 1.2019. Journal of the National Comprehensive Cancer Network. 2019; 17: 896–909.

[23] Noriyuki K, Makoto Y, Seiji I, Fumiaki T, Hirofumi M, Eizo K, et al. Japanese Gynecologic Oncology Group. Long-term results of dosedense paclitaxel and carboplatin versus conventional paclitaxel and carboplatin for treatment of advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (JGOG 3016): a randomised, controlled, open-label trial. The Lancet Oncology. 2013; 14: 1020–1026.

[24] John KC, Mark FB, Richard TP, Helen H, Michael JB, Joan LW, et al. Weekly vs. every-3-week paclitaxel and carboplatin for ovarian cancer. The New England Journal of Medicine. 2016; 374: 738–748.

[25] Reem DM, Robert DM, Richard JE, Andrew RC, Gordon CJ. First-Line Management of Advanced High-Grade Serous Ovarian Cancer. Current Oncology Reports. 2020; 22: 64.

[26] Dan Z, Jiang YX, Luo SJ, Rong Z, Jiang QX, Hua LH. Serum CA125 levels predict outcome of interval debulking surgery after neoadjuvant chemotherapy in patients with advanced ovarian cancer. Clinica Chimica Acta. 2018; 484: 32–35.

[27] Timmermans M, Zwakman N, Sonke GS, Van de Vijver KK, Duk MJ, van der Aa MA, et al. Perioperative change in CA125 is an independent prognostic factor for improved clinical outcome in advanced ovarian cancer. European Journal of Obstetrics, Gynecology, and Reproductive Biology. 2019; 240: 364–369.

[28] Nienke Z, van de Laar R, Toon VG, Petra LMZ, Marc PML S, Isabel F, et al. Perioperative changes in serum CA125 levels: a prognostic factor for disease-specific survival in patients with ovarian cancer. Journal of Gynecologic Oncology. 2017; 28: e7.

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