Annals of Surgical Oncology

, Volume 24, Issue 12, pp 3640–3646 | Cite as

Conversion to Complete Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Malignant Peritoneal Mesothelioma After Bidirectional Chemotherapy

  • Florence Le Roy
  • Maximiliano GelliEmail author
  • Antoine Hollebecque
  • Charles Honoré
  • Valerie Boige
  • Peggy Dartigues
  • Leonor Benhaim
  • David Malka
  • Michel Ducreux
  • Dominique Elias
  • Diane Goéré
Gastrointestinal Oncology



This report aims to describe preliminary results concerning secondary resectability after bidirectional chemotherapy for initially unresectable malignant peritoneal mesothelioma (MPM).


Between January 2013 and January 2016, 20 consecutive patients treated for diffuse MPM not suitable for upfront surgery received bidirectional chemotherapy associating intraperitoneal and systemic chemotherapy. Evaluation of the response to chemotherapy was assessed clinically and by laparoscopy.


The median peritoneal cancer index (PCI) score at staging laparoscopy was 27 (range 15–39). Altogether, 118 intraperitoneal chemotherapy cycles were administered without any specific adverse catheter-related event. Concerning tolerance, 85% of the patients experienced no pain or mild pain during chemotherapy administration. The clinical response rate was 60% after a median of three chemotherapy cycles. At laparoscopic reevaluation, the median PCI was 18 (range 0–35), and a secondary resectability was considered for 55% of the patients. Complete cytoreduction surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC) was finally achieved for 10 patients (50%), with a median intraoperative PCI score of 14 (range 6–30). After a median follow-up period of 18 months, the 2-year overall survival rate was 83.3% for the patients treated by CRS followed by HIPEC and 44% for the patients treated by bidirectional chemotherapy.


Bidirectional chemotherapy is a promising, well-tolerated treatment capable of increasing the resection rate for selected patients with diffuse MPM initially considered as unresectable or borderline resectable. For patients with definitively unresectable disease, bidirectional chemotherapy achieves a higher clinical response rate.



The authors acknowledge Lorna Saint Ange for editing.


  1. 1.
    Poinsot P, Collardeau Frachon S, Restier L, et al. Childhood/adult-onset lysosomal acid lipase deficiency: a serious metabolic and vascular phenotype beyond liver disease-four new pediatric cases. J Clin Lipidol. 2017;11:167–77.CrossRefPubMedGoogle Scholar
  2. 2.
    Markman M, Kelsen D. Efficacy of cisplatin-based intraperitoneal chemotherapy as treatment of malignant peritoneal mesothelioma. J Cancer Res Clin Oncol. 1992;118:547–50.CrossRefPubMedGoogle Scholar
  3. 3.
    Neumann V, Muller KM, Fischer M. Peritoneal mesothelioma: incidence and etiology. Der Pathologe. 1999;20:169–76.CrossRefPubMedGoogle Scholar
  4. 4.
    Eltabbakh GH, Piver MS, Hempling RE, Recio FO, Intengen ME. Clinical picture, response to therapy, and survival of women with diffuse malignant peritoneal mesothelioma. J Surg Oncol. 1999;70:6–12.CrossRefPubMedGoogle Scholar
  5. 5.
    Janne PA, Wozniak AJ, Belani CP, et al. Open-label study of pemetrexed alone or in combination with cisplatin for the treatment of patients with peritoneal mesothelioma: outcomes of an expanded access program. Clin Lung Cancer. 2005;7:40–6.CrossRefPubMedGoogle Scholar
  6. 6.
    Carteni G, Manegold C, Garcia GM, et al. Malignant peritoneal mesothelioma: results from the International Expanded Access Program using pemetrexed alone or in combination with a platinum agent. Lung Cancer. 2009;64:211–8.CrossRefPubMedGoogle Scholar
  7. 7.
    Deraco M, Baratti D, Hutanu I, Bertuli R, Kusamura S. The role of perioperative systemic chemotherapy in diffuse malignant peritoneal mesothelioma patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Ann Surg Oncol. 2013;20:1093–100.CrossRefPubMedGoogle Scholar
  8. 8.
    Kepenekian V, Elias D, Passot G, et al. Diffuse malignant peritoneal mesothelioma: evaluation of systemic chemotherapy with comprehensive treatment through the RENAPE database: multi-institutional retrospective study. Eur J Cancer. 2016;65:69–79.CrossRefPubMedGoogle Scholar
  9. 9.
    Hasovits C, Clarke S. Pharmacokinetics and pharmacodynamics of intraperitoneal cancer chemotherapeutics. Clin Pharmacokinet. 2012;51:203–24.CrossRefPubMedGoogle Scholar
  10. 10.
    Young RC, Brady MF, Nieberg RK, et al. Adjuvant treatment for early ovarian cancer: a randomized phase III trial of intraperitoneal 32P or intravenous cyclophosphamide and cisplatin: a gynecologic oncology group study. J Clin Oncol. 2003;21:4350–5.CrossRefPubMedGoogle Scholar
  11. 11.
    Walker JL, Armstrong DK, Huang HQ, 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. Gynecol Oncol. 2006;100:27–32.CrossRefPubMedGoogle Scholar
  12. 12.
    Markman M, Bundy BN, Alberts DS, et al. Phase III trial of standard-dose intravenous cisplatin plus paclitaxel versus moderately high-dose carboplatin followed by intravenous paclitaxel and intraperitoneal cisplatin in small-volume stage III ovarian carcinoma: an intergroup study of the Gynecologic Oncology Group, Southwestern Oncology Group, and Eastern Cooperative Oncology Group. J Clin Oncol. 2001;19:1001–7.CrossRefPubMedGoogle Scholar
  13. 13.
    Jacquet P, Sugarbaker PH. Clinical research methodologies in diagnosis and staging of patients with peritoneal carcinomatosis. Cancer Treat Res. 1996;82:359–74.CrossRefPubMedGoogle Scholar
  14. 14.
    Trotti A, Colevas AD, Setser A, et al. CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol. 2003;13:176–81.CrossRefPubMedGoogle Scholar
  15. 15.
    Sugarbaker PH. Peritonectomy procedures. Ann Surg. 1995;221:29–42.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Elias D, Goere D, Blot F, et al. Optimization of hyperthermic intraperitoneal chemotherapy with oxaliplatin plus irinotecan at 43 degrees C after compete cytoreductive surgery: mortality and morbidity in 106 consecutive patients. Ann Surg Oncol. 2007;14:1818–24.CrossRefPubMedGoogle Scholar
  17. 17.
    Elias D, Matsuhisa T, Sideris L, et al. Heated intraoperative intraperitoneal oxaliplatin plus irinotecan after complete resection of peritoneal carcinomatosis: pharmacokinetics, tissue distribution, and tolerance. Ann Oncol. 2004;15:1558–65.CrossRefPubMedGoogle Scholar
  18. 18.
    Elias D, Bonnay M, Puizillou JM, et al. Heated intraoperative intraperitoneal oxaliplatin after complete resection of peritoneal carcinomatosis: pharmacokinetics and tissue distribution. Ann Oncol. 2002;13:267–72.CrossRefPubMedGoogle Scholar
  19. 19.
    Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240:205–13.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Yan TD, Deraco M, Baratti D, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for malignant peritoneal mesothelioma: multi-institutional experience. J Clin Oncol. 2009;27:6237–42.CrossRefPubMedGoogle Scholar
  21. 21.
    Dedrick RL, Myers CE, Bungay PM, DeVita VT Jr. Pharmacokinetic rationale for peritoneal drug administration in the treatment of ovarian cancer. Cancer Treat Rep. 1978;62:1–11.Google Scholar
  22. 22.
    Jaaback K, Johnson N, Lawrie TA. Intraperitoneal chemotherapy for the initial management of primary epithelial ovarian cancer. Cochrane Database Syst Rev. 2016;1:CD005340.Google Scholar
  23. 23.
    Pestieau SR, Stuart OA, Sugarbaker PH. Multi-targeted antifolate (MTA): pharmacokinetics of intraperitoneal administration in a rat model. Eur J Surg Oncol. 2000;26:696–700.CrossRefPubMedGoogle Scholar
  24. 24.
    Bijelic L, Stuart OA, Sugarbaker P. Adjuvant bidirectional chemotherapy with intraperitoneal pemetrexed combined with intravenous cisplatin for diffuse malignant peritoneal mesothelioma. Gastroenterol Res Pract. 2012;2012:890450.PubMedPubMedCentralGoogle Scholar
  25. 25.
    Pestieau SR, Belliveau JF, Griffin H, Stuart OA, Sugarbaker PH. Pharmacokinetics of intraperitoneal oxaliplatin: experimental studies. J Surg Oncol. 2001;76:106–14.CrossRefPubMedGoogle Scholar
  26. 26.
    Henretta MS, Anderson CL, Angle JF, Duska LR. It’s not just for laparoscopy anymore: use of insufflation under ultrasound and fluoroscopic guidance by interventional radiologists for percutaneous placement of intraperitoneal chemotherapy catheters. Gynecol Oncol. 2011;123:342–5.CrossRefPubMedGoogle Scholar
  27. 27.
    Greben CR, Goldstein GE, Lovecchio J, et al. Percutaneous insertion of peritoneal ports. Int J Gynecol Cancer. 2012;22:328–31.CrossRefPubMedGoogle Scholar
  28. 28.
    Faron M, Macovei R, Goere D, Honore C, Benhaim L, Elias D. Linear relationship of peritoneal cancer index and survival in patients with peritoneal metastases from colorectal cancer. Ann Surg Oncol. 2016;23:114–9.CrossRefPubMedGoogle Scholar
  29. 29.
    Hubert J, Thiboutot E, Dube P, Cloutier AS, Drolet P, Sideris L. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy with oxaliplatin for peritoneal mesothelioma: preliminary results and survival analysis. Surg Oncol. 2015;24:41–6.CrossRefPubMedGoogle Scholar
  30. 30.
    Cashin PH, Graf W, Nygren P, Mahteme H. Cytoreductive surgery and intraperitoneal chemotherapy for colorectal peritoneal carcinomatosis: prognosis and treatment of recurrences in a cohort study. Eur J Surg Oncol. 2012;38:509–15.CrossRefPubMedGoogle Scholar
  31. 31.
    Elias D, Gilly F, Boutitie F, et al. Peritoneal colorectal carcinomatosis treated with surgery and perioperative intraperitoneal chemotherapy: retrospective analysis of 523 patients from a multicentric French study. J Clin Oncol. 2010;28:63–8.CrossRefPubMedGoogle Scholar
  32. 32.
    da Silva RG, Sugarbaker PH. Analysis of prognostic factors in seventy patients having a complete cytoreduction plus perioperative intraperitoneal chemotherapy for carcinomatosis from colorectal cancer. J Am Coll Surg. 2006;203:878–86.CrossRefPubMedGoogle Scholar
  33. 33.
    Charrier T, Passot G, Peron J, et al. Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy with oxaliplatin increases the risk of postoperative hemorrhagic complications: analysis of predictive factors. Ann Surg Oncol. 2016;23:2315–22.CrossRefPubMedGoogle Scholar
  34. 34.
    Pomel C, Ferron G, Lorimier G, et al. Hyperthermic intraperitoneal chemotherapy using oxaliplatin as consolidation therapy for advanced epithelial ovarian carcinoma: results of a phase II prospective multicentre trial. CHIPOVAC study. Eur J Surg Oncol. 2010;36:589–93.CrossRefPubMedGoogle Scholar
  35. 35.
    Elias D, Bedard V, Bouzid T, et al. Malignant peritoneal mesothelioma: treatment with maximal cytoreductive surgery plus intraperitoneal chemotherapy. Gastroenterol Clin Biol. 2007;31:784–8.CrossRefPubMedGoogle Scholar
  36. 36.
    Yonemura Y, Ishibashi H, Hirano M, et al. Effects of neoadjuvant laparoscopic hyperthermic intraperitoneal chemotherapy and neoadjuvant intraperitoneal/systemic chemotherapy on peritoneal metastases from gastric cancer. Ann Surg Oncol. 2017;24:478–85.CrossRefPubMedGoogle Scholar
  37. 37.
    Yonemura Y, Elnemr A, Endou Y, et al. Effects of neoadjuvant intraperitoneal/systemic chemotherapy (bidirectional chemotherapy) for the treatment of patients with peritoneal metastasis from gastric cancer. Int J Surg Oncol. 2012;2012:148420.PubMedPubMedCentralGoogle Scholar

Copyright information

© Society of Surgical Oncology 2017

Authors and Affiliations

  • Florence Le Roy
    • 1
  • Maximiliano Gelli
    • 2
    Email author
  • Antoine Hollebecque
    • 1
  • Charles Honoré
    • 2
  • Valerie Boige
    • 1
  • Peggy Dartigues
    • 3
  • Leonor Benhaim
    • 2
  • David Malka
    • 1
  • Michel Ducreux
    • 1
  • Dominique Elias
    • 2
  • Diane Goéré
    • 2
  1. 1.Department of Medical OncologyGustave RoussyVillejuif CedexFrance
  2. 2.Department of Visceral and Oncological SurgeryGustave RoussyVillejuif CedexFrance
  3. 3.Department of PathologyGustave RoussyVillejuif CedexFrance

Personalised recommendations