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Cancer Chemotherapy and Pharmacology

Published in:

01-04-2018 | Original Article

Incidence of leukopenia and thrombocytopenia with cisplatin plus mitomycin-c versus melphalan in patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC)

Authors: Hakeam A. Hakeam, Amal Arab, Ayman Azzam, Zyad Alyahya, Abdelmoneim M. Eldali, Tarek Amin

Published in: Cancer Chemotherapy and Pharmacology | Issue 4/2018

Abstract

Introduction

Cytopenia after hyperthermic intraperitoneal chemotherapy (HIPEC) with cytoreductive surgery (CRS) has been reported in non-comparative studies with various chemotherapeutic regimens. This study compared the incidence of leukopenia and thrombocytopenia in patients who underwent CRS/HIPEC and received melphalan or cisplatin plus mitomycin-c (CIS + MMC).

Methods

This retrospective study included patients who underwent CRS/HIPEC at King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia from March 2011 to March 2017 and received melphalan 60 mg/m² or CIS 100 mg/m² combined with MMC 30 mg/m². Incidences and severity of leukopenia, neutropenia, thrombocytopenia, and anemia were compared between groups.

Results

This study included 46 patients who received CIS + MMC and 35 patients who received melphalan. The leukopenia incidence was 25.7% in the melphalan group and 17.3% in the CIS + MMC group (P = 0.362), with one patient (2.8%) in the melphalan group developed grade V leukopenia. The number of days to leukocyte nadir was 32.8 days for CIS + MMC group compared to 9.8 days for melphalan group(P = 0.035). Thrombocytopenia occurred at a similar rate in the melphalan (60%) and CIS + MMC (68.8%) groups (P = 0.4). Grade III thrombocytopenia developed in 3.2% and 5% of patients in the melphalan and the CIS + MMC groups, respectively. Neutropenia did not occur in any patient. In multivariate analysis, leukopenia predictors were female gender (P = 0.047) and baseline leukocyte counts (P = 0.029). Baseline platelet count predicted thrombocytopenia (P < 0.001).

Conclusions

Melphalan and CIS + MMC regimens were associated with comparable incidences of leukopenia and thrombocytopenia. Severe leukopenia and severe thrombocytopenia were rare following CRS/HIPEC using both chemotherapy regimens.

Sugarbaker PH, Stuart OA, Yoo D (2005) Strategies for management of the peritoneal surface component of cancer: cytoreductive surgery plus perioperative intraperitoneal chemotherapy. J Oncol Pharm Pract 11(3):111–119. https://doi.org/10.1191/1078155205jp157oa CrossRefPubMed

Sugarbaker PH (2010) Surgical responsibilities in the management of peritoneal carcinomatosis. J Surg Oncol 101(8):713–24. https://doi.org/10.1002/jso.21484

Fujimoto S, Takahashi M, Mutou T et al (1997) Improved mortality rate of gastric carcinoma patients with peritoneal carcinomatosis treated with intraperitoneal hyperthermic chemoperfusion combined with surgery. Cancer 79(5):884–891CrossRefPubMed

Elias D, Lefevre JH, Chevalier J et al (2009) Complete cytoreductive surgery plus intraperitoneal chemohyperthermia with oxaliplatin for peritoneal carcinomatosis of colorectal origin. J Clin 27(5):681–685. https://doi.org/10.1200/JCO.2008.19.7160 CrossRef

Ihemelandu C, Mavros MN, Sugarbaker P (2016) Adverse events postoperatively had no impact on long-term survival of patients treated with cytoreductive surgery with heated intraperitoneal chemotherapy for appendiceal cancer with peritoneal metastases. Ann Surg Oncol 23(13):4231–4237. https://doi.org/10.1245/s10434-016-5355-4 CrossRefPubMed

de Lima Vazquez V, Stuart OA, Mohamed F et al (2003) Extent of parietal peritonectomy does not change intraperitoneal chemotherapy pharmacokinetics. Cancer Chemother Pharmacol 52(2):108–112. https://doi.org/10.1007/s00280-003-0626-8 CrossRefPubMed

Dedrick RL, Myers CE, Bungay PM et al (1978) Pharmacokinetic rationale for peritoneal drug administration in the treatment of ovarian cancer. Cancer Treat Rep 62(1):1–11PubMed

Jacquet P, Sugarbaker PH (1996) Peritoneal-plasma barrier. Cancer Treat Res 82:53–63CrossRefPubMed

Van der Speeten K, Stuart OA, Sugarbaker PH (2009) Using pharmacologic data to plan clinical treatments for patients with peritoneal surface malignancy. Curr Drug Discov Technol 6(1):72–81CrossRefPubMedPubMedCentral

10.

Sugarbaker PH, Alderman R, Edwards G et al (2006) Prospective morbidity and mortality assessment of cytoreductive surgery plus perioperative intraperitoneal chemotherapy to treat peritoneal dissemination of appendiceal mucinous malignancy. Ann Surg Oncol 13(5):635–644. https://doi.org/10.1245/ASO.2006.03.079 CrossRefPubMed

11.

Kemmel V, Mercoli HA, Meyer N et al (2015) Mitomycin C pharmacokinetics as predictor of severe neutropenia in hyperthermic intraperitoneal therapy. Ann Surg Oncol 22(Suppl 3):S873–S879. https://doi.org/10.1245/s10434-015-4679-9 CrossRefPubMed

12.

van Ruth S, Mathot RA, Sparidans RW et al (2004) Population pharmacokinetics and pharmacodynamics of mitomycin during intraoperative hyperthermic intraperitoneal chemotherapy. Clin Pharmacokinet 43(2):131–143. https://doi.org/10.2165/00003088-200443020-00005 CrossRefPubMed

13.

Kusamura S, Dominique E, Baratti D et al (2008) Drugs, carrier solutions and temperature in hyperthermic intraperitoneal chemotherapy. J Surg Oncol 98(4):247–252. https://doi.org/10.1002/jso.210515 CrossRefPubMed

14.

van Ruth S, Verwaal VJ, Zoetmulder FA (2003) Pharmacokinetics of intraperitoneal mitomycin C. Surg Oncol Clin N Am 12(3):771–780CrossRefPubMed

15.

Murata S, Yamamoto H, Naitoh H et al (2017) Feasibility and safety of hyperthermic intraperitoneal chemotherapy using 5-fluorouracil combined with cisplatin and mitomycin C in patients undergoing gastrectomy for advanced gastric cancer. J Surg Oncol. https://doi.org/10.1002/jso.24771

16.

Kusamura S, Baratti D, Younan R et al (2007) Impact of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy on systemic toxicity. Ann Surg Oncol 14(9):2550–2558. https://doi.org/10.1245/s10434-007-9429-1 CrossRefPubMed

17.

Cotte E, Colomban O, Guitton J et al (2011) Population pharmacokinetics and pharmacodynamics of cisplatinum during hyperthermic intraperitoneal chemotherapy using a closed abdominal procedure. J Clin Pharmacol 51(1):9–18. https://doi.org/10.1177/0091270009360980 CrossRefPubMed

18.

Sardi A, Jimenez W, Nieroda C et al (2014) Melphalan: a promising agent in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Ann Surg Oncol 21(3):908–914. https://doi.org/10.1245/s10434-013-3407-6 CrossRefPubMed

19.

Bijelic L, Sugarbaker PH, Stuart OA (2012) Hyperthermic intraperitoneal chemotherapy with melphalan: a summary of clinical and pharmacological data in 34 patients. Gastroenterol Res Pract 2012:827534. https://doi.org/10.1155/2012/827534 PubMedPubMedCentral

20.

Lambert LA, Armstrong TS, Lee JJ et al (2009) Incidence, risk factors, and impact of severe neutropenia after hyperthermic intraperitoneal mitomycin C. Ann Surg Oncol 16(8):2181–2187. https://doi.org/10.1245/s10434-009-0523-4 CrossRefPubMedPubMedCentral

21.

Sugarbaker PH, Stuart OA, Carmignani CP (2006) Pharmacokinetic changes induced by the volume of chemotherapy solution in patients treated with hyperthermic intraperitoneal mitomycin C. Cancer Chemother Pharmacol 57(5):703–708. https://doi.org/10.1007/s00280-005-0074-8 CrossRefPubMed

22.

Institute NC. CTEP: NCI Guidance on CTC Terminology Applications: National Cancer Institute; Bethesda, MD (2009) https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.html. Accessed date 01 Aug 2017

23.

Sugarbaker PH (1995) Peritonectomy procedures. Ann Surg 221(1):29–42CrossRefPubMedPubMedCentral

24.

Zein TA, Friedberg N, Kim H (1986) Bone marrow suppression after intravesical mitomycin C treatment. J Urol 136(2):459–460CrossRefPubMed

25.

Feferman Y, Bhagwandin S, Kim J et al (2017) Conflicting Data on the Incidence of Leukopenia and Neutropenia After Heated Intraperitoneal Chemotherapy with Mitomycin C. Ann Surg Oncol 24(13):3831–3836. https://doi.org/10.1245/s10434-017-6112-z CrossRefPubMed

26.

Glehen O, Cotte E, Kusamura S et al (2008) Hyperthermic intraperitoneal chemotherapy: nomenclature and modalities of perfusion. J Surg Oncol 98(4):242–246. https://doi.org/10.1002/jso.21061 CrossRefPubMed

27.

Raspe C, Flother L, Schneider R et al (2017) Best practice for perioperative management of patients with cytoreductive surgery and HIPEC. Eur J Surg Oncol 43(6):1013–1027. https://doi.org/10.1016/j.ejso.2016.09.008 CrossRefPubMed

28.

Facy O, Combier C, Poussier M et al (2015) High pressure does not counterbalance the advantages of open techniques over closed techniques during heated intraperitoneal chemotherapy with oxaliplatin. Surgery 157(1):72–78. https://doi.org/10.1016/j.surg.2014.06.006 CrossRefPubMed

29.

Valle SJ, Alzahrani NA, Liauw W et al (2016) Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Methodology, Drugs and Bidirectional Chemotherapy. Indian J Surg Oncol 7(2):152–159. https://doi.org/10.1007/s13193-016-0498-0 CrossRefPubMedPubMedCentral

30.

Scaringi S, Kianmanesh R, Sabate JM et al (2008) Advanced gastric cancer with or without peritoneal carcinomatosis treated with hyperthermic intraperitoneal chemotherapy: a single western center experience. Eur J Surg Oncol 34(11):1246–1252. https://doi.org/10.1016/j.ejso.2007.12.003 CrossRefPubMed

31.

Noe DA, Graham SM, Luff R et al (1982) Platelet counts during rapid massive transfusion. Transfusion 22(5):392–395CrossRefPubMed

32.

Chua TC, Moran BJ, Sugarbaker PH et al (2012) 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 30(20):2449–2456. https://doi.org/10.1200/JCO.2011.39.7166 CrossRefPubMed

Title: Incidence of leukopenia and thrombocytopenia with cisplatin plus mitomycin-c versus melphalan in patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC)
Authors: Hakeam A. Hakeam
Amal Arab
Ayman Azzam
Zyad Alyahya
Abdelmoneim M. Eldali
Tarek Amin
Publication date: 01-04-2018
Publisher: Springer Berlin Heidelberg
Published in: Cancer Chemotherapy and Pharmacology / Issue 4/2018
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-018-3537-4

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Abstract

Introduction

Methods

Results

Conclusions

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