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Conflicting Data on the Incidence of Leukopenia and Neutropenia After Heated Intraperitoneal Chemotherapy with Mitomycin C

  • Gastrointestinal Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

During heated intraperitoneal chemotherapy (HIPEC), neutropenia rates of 20 to 40% have been reported when mitomycin C (MMC) is dosed by weight or body surface area (BSA). This study investigated the authors’ HIPEC experience using a fixed 40-mg dose of MMC, per consensus guidelines, and analyzed predictors for severe leukopenia and neutropenia.

Methods

Patients who underwent MMC-HIPEC from 2007 to 2016 at a single tertiary care center were retrospectively reviewed.

Results

Among 314 MMC-HIPEC cases, 72 patients in the early era of the authors’ program received routine prophylactic postoperative granulocyte-colony-stimulating factor (GCSF). This early cohort had five severe leukopenic reactions and one neutropenic reaction. In the subsequent 242 cases without GCSF prophylaxis, severe leukopenia developed in 16 patients (7%), with neutropenia occurring in 11 (4.5%) of these cases. A history of prior systemic chemotherapy was noted in 9 (56%) of the 16 leukopenic patients compared with 112 (46%) of the patients who had no leukopenia (nonsignificant difference). The median nadir of leukopenia was 5 days (range 1–11 days). Of the 11 neutropenic patients, 6 received therapeutic GCSF, and 5 recovered without intervention. The 30-day postoperative mortality of the patients with leukopenia was 0%.

Conclusion

In this study, the incidence of neutropenia after HIPEC with 40 mg of MMC was markedly lower than reported in the literature for doses adjusted by BSA or weight. The authors report that GCSF is not necessary for routine prophylaxis of all MMC-HIPEC patients. The findings suggest that a fixed 40-mg dose of MMC allows HIPEC to be performed with less risk of immunosuppression.

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References

  1. Turaga K, Levine E, Barone R, et al. Consensus Guidelines from The American Society of Peritoneal Surface Malignancies on standardizing the delivery of hyperthermic intraperitoneal chemotherapy (HIPEC) in colorectal cancer patients in the United States. Ann Surg Oncol. 2014;21:1501–5.

    Article  CAS  PubMed  Google Scholar 

  2. Gonzalez-Moreno S. Peritoneal surface oncology: a progress report. Eur J Surg Oncol. 2006;32:593–6.

    Article  PubMed  Google Scholar 

  3. Chua TC, Moran BJ, Sugarbaker PH, et al. Early and long-term outcome data of patients with pseudomyxoma peritonei from appendiceal origin treated by a strategy of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. J Clin Oncol. 2012;30:2449–56.

    Article  PubMed  Google Scholar 

  4. 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.

    Article  PubMed  Google Scholar 

  5. Bartlett EK, Meise C, Roses RE, Fraker DL, Kelz RR, Karakousis GC. Morbidity and mortality of cytoreduction with intraperitoneal chemotherapy: outcomes from the ACS NSQIP database. Ann Surg Oncol. 2014;21:1494–500.

    Article  PubMed  Google Scholar 

  6. Polanco PM, Ding Y, Knox JM, et al. Institutional learning curve of cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion for peritoneal malignancies. Ann Surg Oncol. 2015;22:1673–9.

    Article  PubMed  Google Scholar 

  7. Macri A, Arcoraci V, Belgrano V, et al. Short-term outcome of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: preliminary analysis of a multicentre study. Anticancer Res. 2014;34:5689–93.

    PubMed  Google Scholar 

  8. Desantis M, Bernard JL, Casanova V, et al. Morbidity, mortality, and oncological outcomes of 401 consecutive cytoreductive procedures with hyperthermic intraperitoneal chemotherapy (HIPEC). Langenbecks Arch Surg. 2015;400:37–48.

    Article  PubMed  Google Scholar 

  9. Sartorelli AC, Hodnick WF, Belcourt MF, Tomasz M, Haffty B, Fischer JJ, Rockwell S. Mitomycin C: a prototype bioreductive agent. Oncol Res. 1994;6:501–8.

    CAS  PubMed  Google Scholar 

  10. Tomasz, M. Mitomycin C: small fast and deadly (but very selective). Chem Biol. 1995;2:575–9.

    Article  CAS  PubMed  Google Scholar 

  11. Van Ruth S, Verwaal VJ, Zoetmulder FAN. Pharmacokinetics of intraperitoneal mitomycin C. Surg Oncol Clin North Am. 2003;12:771–80.

    Article  Google Scholar 

  12. Katz MH, Barone RM. The rationale of perioperative intraperitoneal chemotherapy in the treatment of peritoneal surface malignancies. Surg Oncol Clin North Am. 2003;12:673–88.

    Article  Google Scholar 

  13. Kuzuya T, Yamauchi M, Ito A, Hasegawa M, Hasegawa T, Nabeshima T. Pharmacokinetic characteristics of 5-fluorouracil and mitomycin C in intraperitoneal chemotherapy. J Pharm Pharmacol. 1994;46:685–9.

    Article  CAS  PubMed  Google Scholar 

  14. Teicher BA, Kowal CD, Kennedy KA, Sartorelli AC. Enhancement by hyperthermia of the in vitro cytotoxicity of mitomycin C toward hypoxic tumor cells. Cancer Res. 1981;41:1096–9.

    CAS  PubMed  Google Scholar 

  15. Lambert LA, Armstrong TS, Lee JJ, et al. Incidence, risk factors, and impact of severe neutropenia after hyperthermic intraperitoneal mitomycin C. Ann Surg Oncol. 2009;16:2181–7.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Sugarbaker PH, Alderman R, Edwards G, Marquardt CE, Gushchin V, Esquivel J, Chang D. Prospective morbidity and mortality assessment of cytoreductive surgery plus perioperative intraperitoneal chemotherapy to treat peritoneal dissemination of appendiceal mucinous malignancy. Ann Surg Oncol. 2006;13:635–44.

    Article  PubMed  Google Scholar 

  17. Kemmel V, Mercoli HA, Meyer N, Brumaru D, Romain B, Lessinger JM, Brigand C. Mitomycin C pharmacokinetics as predictor of severe neutropenia in hyperthermic intraperitoneal therapy. Ann Surg Oncol. 2015;22:S873–9.

    Article  PubMed  Google Scholar 

  18. National Cancer Institute (NCI) Common terminology criteria for adverse events (2012) version 3.0. https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcaev3.pdf. Accessed 8 May 2017

  19. Clavien PA, Barkun J, de Oliveira ML, et al. The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg. 2009;250:187–96.

    Article  PubMed  Google Scholar 

  20. Franssen B, Tabrizian P, Weinberg A, Romanoff A, Tuvin D, Labow D, Sarpel U. Outcome of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy on patients with diaphragmatic involvement. Ann Surg Oncol. 2015;22:1639–44.

    Article  PubMed  Google Scholar 

  21. Tabrizian P, Shrager B, Jibara G, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis: outcomes from a single tertiary institution. J Gastrointest Surg. 2014;18:1024–31.

    Article  PubMed  Google Scholar 

  22. Jacquet P, Sugarbaker PH. Clinical research methodologies in diagnosis and staging of patients with peritoneal carcinomatosis. In: Sugarbaker PH, editor. Peritoneal carcinomatosis: principles of management. Kluwer Academic Publishers, Boston; 1996. pp. 359–74.

  23. Chua TC, Yan TD, Saxena A, Morris DL. Should the treatment of peritoneal carcinomatosis by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy still be regarded as a highly morbid procedure? Ann Surg. 2009;249:900–7.

    Article  PubMed  Google Scholar 

  24. 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. Am J Coll Surg. 2006;203:878–86.

    Article  Google Scholar 

  25. Sugarbaker PH, Stuart OA, Eger C. Pharmacokinetics of hyperthermic intrathoracic chemotherapy following pleurectomy and decortication. Gastroenterol Res Pract. 2012;2012:471205.

    PubMed  PubMed Central  Google Scholar 

  26. Esquivel J. Technology of hyperthermic intraperitoneal chemotherapy in the United States, Europe, China, Japan and Korea. Cancer J. 2009;15:249–54.

    PubMed  Google Scholar 

  27. Verwaal VJ, van Ruth S, Witkamp A, Boot H, van Slooten G, Zoetmulder FA. Long-term survival of peritoneal carcinomatosis of colorectal origin. Ann Surg Oncol. 2005;12:65–71.

    Article  PubMed  Google Scholar 

  28. Shen P, Hawksworth J, Lovato J, et al. Cytoreductive surgery and intraperitoneal hyperthermic chemotherapy with mitomycin C for peritoneal carcinomatosis from non-appendiceal colorectal carcinoma. Ann Surg Oncol. 2004;11:178–86.

    Article  PubMed  Google Scholar 

  29. Schnake KJ, Sugarbaker PH, Yoo D. Neutropenia following perioperative intraperitoneal chemotherapy. Tumori. 1999;85:41–6.

    CAS  PubMed  Google Scholar 

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The authors declare no potential conflicts of interest.

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Correspondence to Umut Sarpel MD, MSc.

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Feferman, Y., Bhagwandin, S., Kim, J. et al. Conflicting Data on the Incidence of Leukopenia and Neutropenia After Heated Intraperitoneal Chemotherapy with Mitomycin C. Ann Surg Oncol 24, 3831–3836 (2017). https://doi.org/10.1245/s10434-017-6112-z

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  • DOI: https://doi.org/10.1245/s10434-017-6112-z

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