Article Data

  • Views 506
  • Dowloads 144

Reviews

Open Access Special Issue

Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in the Management of Advanced Ovarian Cancer. A Literature Review

  • Valentina Ghirardi1
  • Rita Trozzi1,2
  • Elena Giudice1,2
  • Giovanni Scambia1,2
  • Anna Fagotti1,2,*,

1Division of Gynecologic Oncology, Fondazione Policlinico Universitario A. Gemelli - IRCCS, 00168 Rome, Italy

2Universita’ Cattolica del Sacro Cuore, 00151 Rome, Italy

DOI: 10.31083/j.ejgo4302039 Vol.43,Issue 2,April 2022 pp.335-340

Submitted: 27 December 2021 Accepted: 19 January 2022

Published: 15 April 2022

(This article belongs to the Special Issue Radical Surgery in Ovarian Cancer)

*Corresponding Author(s): Anna Fagotti E-mail: anna.fagotti@unicatt.it

Abstract

The rationale behind the use of hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery is the association between pharmacological activity of chemotherapy delivered to the peritoneal cavity with the enhanced cytotoxic effect of hyperthermia. Data on the efficacy of HIPEC in the primary debulking surgery (PDS) setting are still controversial and limited by the small sample size of most of the studies, the inclusion of different treatment settings and chemotherapy regimens. Among the ongoing prospective trials, only the OVHIPEC-2 trial is investigating exclusively patients submitted to PDS ± HIPEC with cisplatin 100 mg/m22 and results are expected by 2026. On the interval debulking surgery (IDS) setting high quality data are coming from the result of the OVHIPEC-1 trial, which demonstrated a survival advantage of nearly 4 months in median progression-free survival (PFS) (14.2 months vs. 10.7 months; p = 0.003) and almost 12 months in median overall survival (OS) (45.7 months vs. 33.9 months; p = 0.02) for HIPEC treated patients (cisplatin 100 mg/m22) compared to no-HIPEC group, with comparable morbidity. However, due to some criticisms raised to the results of OVHIPEC-1 trial, the ESMO-ESGO guidelines recommended not to consider HIPEC as standard therapy until results from ongoing randomized control trials (RCTs) are provided. On the contrary, for the National Comprehensive cancer network (NCCN) guidelines HIPEC can be considered at the time of IDS. Similarly, data supporting the role of HIPEC in association with surgery in case of recurrent disease appear to be controversial in terms of patients and selection and intraperitoneal chemotherapy regimen. Indeed, despite the positive results coming from a prospective randomized trial, they appear to be biased by the inclusion of both platinum sensitive and resistant disease and the lack of information on PFS. Those results are in contrast with data coming from another prospective trial, which failed to demonstrate a survival gain of recurrent ovarian cancer patients treated with secondary cytoreductive surgery + HIPEC with carboplatin (800 mg/m22 for 90 min) compared to women submitted to cytoreduction only. Again, in this subgroup of patients data of ongoing RCTs are awaited to assess the impact on survival of HIPEC administration in case of recurrent disease.


Keywords

ovarian cancer; HIPEC; primary debulking surgery; interval debulking surgery; recurrent disease

Cite and Share

Valentina Ghirardi,Rita Trozzi,Elena Giudice,Giovanni Scambia,Anna Fagotti. Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in the Management of Advanced Ovarian Cancer. A Literature Review. European Journal of Gynaecological Oncology. 2022. 43(2);335-340.

References

[1] Kim SI, Kim JW. Role of surgery and hyperthermic intraperitoneal chemotherapy in ovarian cancer. ESMO Open. 2021; 6: 100149.

[2] Marrelli D, Petrioli R, Cassetti D, D’Ignazio A, Marsili S, Mazzei MA, et al. A novel treatment protocol with 6 cycles of neoadjuvant chemotherapy followed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in stage III primary ovarian cancer. Surgical Oncology. 2021; 37: 101523.

[3] Fader AN, Rose PG. Role of surgery in ovarian carcinoma. Journal of Clinical Oncology. 2007; 25: 2873–2883.

[4] Colombo N, Sessa C, Bois AD, Ledermann J, McCluggage W, McNeish I, et al. ESMO–ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease. Annals of oncology. 2019; 30: 672–705.

[5] Chang S, Hodeib M, Chang J, Bristow RE. Survival impact of complete cytoreduction to no gross residual disease for advanced-stage ovarian cancer: a meta-analysis. Gynecologic Oncology. 2013; 130: 493–498.

[6] Dellinger TH, Han ES. State of the Science: the role of HIPEC in the treatment of ovarian cancer. Gynecologic Oncology. 2021; 160: 364–368.

[7] Vos LMC, Aronson SL, van Driel WJ, Huitema ADR, Schagen van Leeuwen JH, Lok CAR, et al. Translational and pharmacological principles of hyperthermic intraperitoneal chemotherapy for ovarian cancer. Best Practice & Research Clinical Obstetrics & Gynaecology. 2022; 78: 86–102.

[8] van Driel WJ, Koole SN, Sikorska K, Schagen van Leeuwen JH, Schreuder HWR, Hermans RHM, et al. Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer. New England Journal of Medicine. 2018; 378: 230–240.

[9] Coley WB. The treatment of malignant tumors by repeated inoculations of erysipelas. With a report of ten original cases. 1893. Clinical Orthopaedics and Related Research. 1991: 3–11.

[10] Fajardo LF, Egbert B, Marmor J, Hahn GM. Effects of hyper-thermia in a malignant tumor. Cancer. 1980; 45: 613–623.

[11] Facy O, Radais F, Ladoire S, Delroeux D, Tixier H, Ghiringhelli F, et al. Comparison of hyperthermia and adrenaline to enhance the intratumoral accumulation of cisplatin in a murine model of peritoneal carcinomatosis. Journal of Experimental & Clinical Cancer Research. 2011; 30: 4.

[12] Muller M, Chérel M, Dupré P, Gouard S, Collet M, Classe J. Cytotoxic effect of hyperthermia and chemotherapy with platinum salt on ovarian cancer cells: results of an in vitro study. European Surgical Research. 2011; 46: 139–147.

[13] Harima Y, Nagata K, Harima K, Ostapenko VV, Tanaka Y, Sawada S. A randomized clinical trial of radiation therapy versus thermoradiotherapy in stage IIIB cervical carcinoma. International Journal of Hyperthermia. 2001; 17: 97–105.

[14] Barlogie B, Corry PM, Drewinko B. In vitro thermochemotherapy of human colon cancer cells with cisdichlorodiammineplatinum(II) and mitomycin C. Cancer Research. 1980; 40: 1165–1168.

[15] Jain RK. Antiangiogenesis strategies revisited: from starving tumors to alleviating hypoxia. Cancer Cell. 2014; 26: 605–622.

[16] van den Tempel N, Laffeber C, Odijk H, van Cappellen WA, van Rhoon GC, Franckena M, et al. The effect of thermal dose on hyperthermia-mediated inhibition of DNA repair through homologous recombination. Oncotarget. 2017; 8: 44593–44604.

[17] Lim MC, Chang S, Yoo HJ, Nam B, Bristow R, Park S. Randomized trial of hyperthermic intraperitoneal chemotherapy (HIPEC) in women with primary advanced peritoneal, ovarian, and tubal cancer. Journal of Clinical Oncology. 2017; 35: 5520–5520.

[18] Paris I, Cianci S, Vizzielli G, Fagotti A, Ferrandina G, Gueli Alletti S, et al. Upfront HIPEC and bevacizumab-containing adjuvant chemotherapy in advanced epithelial ovarian cancer. International Journal of Hyperthermia. 2018; 35: 370–374.

[19] Koole S, van Stein R, Sikorska K, Barton D, Perrin L, Brennan D, et al. Primary cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy (HIPEC) for FIGO stage III epithelial ovarian cancer: OVHIPEC-2, a phase III randomized clinical trial. International Journal of Gynecologic Cancer. 2020; 30: 888–892.

[20] Prat J. Staging classification for cancer of the ovary, fallopian tube, and peritoneum. International Journal of Gynaecology and Obstetrics. 2014; 124: 1–5.

[21] Efficacy of HIPEC in the Treatment of Advanced-Stage Epithelial Ovarian Cancer After Cytoreductive Surgery (EHTASEOCCS). 2017. Available at: https://clinicaltrials.gov/ct2/show/NCT03373058 (Accessed: 16 January 2022).

[22] Phase 3 Trial Evaluating Hyperthermic Intraperitoneal Chemotherapy in Upfront Treatment of Stage IIIC Epithelial Ovarian Cancer (CHORINE). 2012. Available at: https://clinicaltrials.gov/ct2/show/NCT01628380 (Accessed: 16 January 2022).

[23] Harter P, du Bois A, Mahner S, Pfisterer J, Ortmann O, Marth C, et al. Statement of the AGO Kommission Ovar, AGO Study Group, NOGGO, AGO Austria and AGO Switzerland Regarding the Use of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Ovarian Cancer. Geburtshilfe Und Frauenheilkunde. 2019; 76: 147–149.

[24] van Driel WJ, Koole SN, Sikorska K, Schagen van Leeuwen JH, Schreuder HWR, Hermans RHM, et al. Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer. The New England Journal of Medicine. 2018; 378: 230–240.

[25] Laplace N, Kepenekian V, Friggeri A, Vassal O, Ranchon F, Rioufol C, et al. Sodium thiosulfate protects from renal impairement following hyperthermic intraperitoneal chemotherapy (HIPEC) with Cisplatin. International Journal of Hyperthermia. 2020; 37: 897–902.

[26] Ghirardi V, Ronsini C, Trozzi R, Di Ilio C, Di Giorgio A, Cianci S, et al. Hyperthermic intraperitoneal chemotherapy in interval debulking surgery for advanced epithelial ovarian cancer: a single‐center, real‐life experience. Cancer. 2020; 126: 5256–5262.

[27] Koole SN, Kieffer JM, K Sikorska, Schagen van Leeuwen JH, Schreuder HWR, Hermans RH, et al. Health-related quality of life after interval cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with stage III ovarian cancer. European Journal of Surgical Oncology. 2021; 47: 101–107.

[28] Koole SN, van Lieshout C, van Driel WJ, van Schagen E, Sikorska K, Kieffer JM, et al. Cost Effectiveness of Interval Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy in Stage III Ovarian Cancer on the Basis of a Randomized Phase III Trial. Journal of Clinical Oncology. 2019; 37: 2041–2050.

[29] Antonio CCP, Alida GG, Elena GG, Rocío GS, Jerónimo MG, Luis ARJ, et al. Cytoreductive Surgery With or Without HIPEC After Neoadjuvant Chemotherapy in Ovarian Cancer: A Phase 3 Clinical Trial. Annals of surgical oncology. 2021: 1–9.

[30] Vergote I, Harter P, Chiva L. Hyperthermic intraperitoneal chemotherapy does not improve survival in advanced ovarian cancer. Cancer. 2019; 125: 4594–4597.

[31] Armstrong DK, Alvarez RD, Bakkum-Gamez JN, Barroilhet L, Behbakht K, Berchuck A, et al. Ovarian Cancer, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology. Journal of the National Comprehensive Cancer Network. 2021; 19: 191–226.

[32] Efficacy of HIPEC as NACT and Postoperative Chemotherapy in the Treatment of Advanced-Stage Epithelial Ovarian Cancer (EHNPCTASEOC). 2017. Available at: https://clinicaltrials.gov /ct2/show/NCT03180177 (Accessed: 16 January 2022).

[33] Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Ovarian Cancer (CHIPPI) (CHIPPI). 2019. Available at: https://cl inicaltrials.gov/ct2/show/NCT03842982 (Accessed: 16 January 2022).

[34] Marrelli D, Petrioli R, Cassetti D, D’Ignazio A, Marsili S, Mazzei MA, et al. A novel treatment protocol with 6 cycles of neoadjuvant chemotherapy followed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in stage III primary ovarian cancer. Surgical Oncology. 2021; 37: 101523.

[35] Coccolini F, Campanati L, Catena F, Ceni V, Ceresoli M, Jimenez Cruz J, et al. Hyperthermic intraperitoneal chemotherapy with cisplatin and paclitaxel in advanced ovarian cancer: a multicenter prospective observational study. Journal of Gynecologic Oncology. 2015; 26: 54–61.

[36] Cancer Therapy Evaluation Program. Common Terminology Criteria for Adverse Events v3.0 (CTCAE) [Internet]. Bethesda, MD: Cancer Therapy Evaluation Program; c2006 [cited 2014 Oct 17]. Available at: http://www.eortc.be/services/doc/ctc/ctca ev3.pdf (Accessed: 16 January 2022).

[37] Spiliotis J, Halkia E, Lianos E, Kalantzi N, Grivas A, Efstathiou E, et al. Cytoreductive surgery and HIPEC in recurrent epithelial ovarian cancer: a prospective randomized phase III study. Annals of Surgical Oncology. 2015; 22: 1570–1575.

[38] Petrillo M, De Iaco P, Cianci S, Perrone M, Costantini B, Ronsini C, et al. Long-Term Survival for Platinum-Sensitive Recurrent Ovarian Cancer Patients Treated with Secondary Cytoreductive Surgery Plus Hyperthermic Intraperitoneal Chemotherapy (HIPEC). Annals of Surgical Oncology. 2016; 23: 1660–1665.

[39] Zivanovic O, Chi DS, Zhou Q, Iasonos A, Konner JA, Makker V, et al. Secondary Cytoreduction and Carboplatin Hyperthermic Intraperitoneal Chemotherapy for Platinum-Sensitive Recurrent Ovarian Cancer: an MSK Team Ovary Phase II Study. Journal of Clinical Oncology. 2021; 39: 2594–2604.

[40] Cytoreductive Surgery and HIPEC in First or Secondary Platinum-resistant Recurrent Ovarian Epithelial Cancer (HIPOVA-01). 2017. Available at: https://clinicaltrials.gov/ct2/show/NCT03220932 (Accessed: 16 January 2022).

[41] Hyperthermic Intra-Peritoneal Chemotherapy (HIPEC) in Relapse Ovarian Cancer Treatment (CHIPOR). 2011. Available at: https://clinicaltrials.gov/ct2/show/NCT01376752 (Accessed: 16 January 2022).

[42] Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Ovarian Cancer Recurrence (HORSE). 2012. Available at: https: //clinicaltrials.gov/ct2/show/NCT01539785 (Accessed: 16 January 2022).

[43] Kamada Y, Hida K, Yonemura Y, Sugarbaker PH, Ghabra S, Ishihara S, et al. The Characteristics of 206 Long-Term Survivors with Peritoneal Metastases from Colorectal Cancer Treated with Curative Intent Surgery: A Multi-Center Cohort from PSOGI. Cancers. 2021; 13: 2964.

[44] Chambers LM, Yao M, Morton M, Gruner M, Chichura A, Horowitz M, et al. Patterns of recurrence in women with advanced and recurrent epithelial ovarian cancer treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Gynecologic Oncology. 2021; 161: 389–395.


Abstracted / indexed in

Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,500 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.

Biological Abstracts Easily discover critical journal coverage of the life sciences with Biological Abstracts, produced by the Web of Science Group, with topics ranging from botany to microbiology to pharmacology. Including BIOSIS indexing and MeSH terms, specialized indexing in Biological Abstracts helps you to discover more accurate, context-sensitive results.

Google Scholar Google Scholar is a freely accessible web search engine that indexes the full text or metadata of scholarly literature across an array of publishing formats and disciplines.

JournalSeek Genamics JournalSeek is the largest completely categorized database of freely available journal information available on the internet. The database presently contains 39226 titles. Journal information includes the description (aims and scope), journal abbreviation, journal homepage link, subject category and ISSN.

Current Contents - Clinical Medicine Current Contents - Clinical Medicine provides easy access to complete tables of contents, abstracts, bibliographic information and all other significant items in recently published issues from over 1,000 leading journals in clinical medicine.

BIOSIS Previews BIOSIS Previews is an English-language, bibliographic database service, with abstracts and citation indexing. It is part of Clarivate Analytics Web of Science suite. BIOSIS Previews indexes data from 1926 to the present.

Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.

Submission Turnaround Time

Conferences

Top