Body surface area predicts plasma oxaliplatin and pharmacokinetic advantage in hyperthermic intraoperative intraperitoneal chemotherapy

Our plain-English summary of Body surface area predicts plasma oxaliplatin and pharmacokinetic advantage in hyperthermic intraoperative intraperitoneal chemotherapy, by J.C. Leinwand, G.E. Bates, J.D. Allendorf, et al (Annals of Surgical Oncology, 2013).

The study

• Authors: J.C. Leinwand, G.E. Bates, J.D. Allendorf, J.A. Chabot, S.N. Lewin, R.N. Taub
• Journal: Annals of Surgical Oncology
• Published: 2013;20(4):1101-4
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) is used to treat peritoneal surface-spreading malignancies to maximize local drug concentrations while minimizing systemic effects. The pharmacokinetic advantage of HIPEC is defined as the intraperitoneal to intravascular ratio of drug concentrations. We hypothesized that body surface area (BSA) would correlate with the pharmacokinetic advantage of HIPEC. Because oxaliplatin is administered in 5 % dextrose, we hypothesized that BSA would correlate with glycemia.

Methods: We collected blood and peritoneal perfusate samples from ten patients undergoing HIPEC with a BSA-based dose of 250 mg/m(2) oxaliplatin, and measured drug concentrations by inductively coupled plasma mass spectrophotometry. We monitored blood glucose for 24 h postoperatively. Areas under concentration-time curves (AUC) were calculated by trapezoidal rule. Pharmacokinetic advantage was calculated by (AUC[peritoneal fluid]/AUC[plasma]). We used linear regression to test for statistical significance.

Results: Higher BSA was associated with lower plasma oxaliplatin AUC (p = 0.0075) and with a greater pharmacokinetic advantage (p = 0.0198) over the 60-minute duration of HIPEC. No statistically significant relationships were found between BSA and blood glucose AUC or peak blood glucose levels.

Conclusions: Higher BSA is correlated with lower plasma drug levels and greater pharmacokinetic advantage in HIPEC, likely because of increased circulating blood volume with inadequate time for equilibration. Plasma glucose levels after oxaliplatin HIPEC were not clearly related to BSA.

In plain English

Researchers at Columbia University Medical Center, New York, measured the drug oxaliplatin in ten patients given heated chemotherapy in the abdomen during surgery (HIPEC). Four had malignant peritoneal mesothelioma, five had pseudomyxoma peritonei and one had peritoneal spread of colon cancer. Each received 250 mg/m2 of oxaliplatin, dosed by body surface area, in 5 % dextrose over 60 minutes. They compared drug levels in blood and abdominal fluid and tracked blood sugar for 24 hours. Larger body surface area was associated with lower blood drug exposure (p = 0.0075) and a higher abdominal-to-blood exposure ratio (p = 0.0198), but not significantly with exposure in abdominal fluid. Body mass index was not significantly related to any drug measure. Nor were body size or fluid volume significantly related to blood sugar, though all had high blood sugar. The authors concluded that body surface area can be used to predict oxaliplatin pharmacokinetics in HIPEC. They suggested circulating blood volume, with too little time for equilibration, as the likely reason. They noted the small group and that toxicity and effectiveness were not prospectively analyzed.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: small clinical pharmacokinetic study (drug levels measured in blood and abdominal fluid during surgery, analyzed by linear regression)
• Who was studied: Ten patients undergoing HIPEC, studied by authors at Columbia University Medical Center, New York: 5 with pseudomyxoma peritonei, 4 with malignant peritoneal mesothelioma, 1 with peritoneal carcinomatosis from colon cancer. They were aged 25 to 79; 7 were female and 3 male (Table 1). The study dates are not stated.
• Exposure: Oxaliplatin chemotherapy at 250 mg/m2 (dosed by body surface area) in 5 % dextrose carrier fluid, circulated at 1 L/min for 60 minutes during surgery. The article does not concern asbestos exposure.
• Main results:
  • Across the ten patients, higher body surface area was associated with lower plasma oxaliplatin AUC (overall drug exposure in blood) over the 60-minute HIPEC, p = 0.0075.
  • Higher body surface area was associated with a greater pharmacokinetic advantage (ratio of abdominal fluid to blood drug exposure), b = 28.7/m2, p = 0.0198. The mean pharmacokinetic advantage was 18.6 (SD 6.8).
  • Higher perfusate (carrier fluid) volume was associated with lower plasma oxaliplatin AUC (b = -30.7, p = 0.0170). Perfusate volume was correlated with body surface area.
  • No statistically significant relationship was found between body surface area and drug exposure in the abdominal fluid. Nor was body mass index significantly related to any of the pharmacokinetic measures.
  • Perfusate volume, body surface area and body mass index were not significantly related to 24-hour blood sugar or to peak blood sugar during surgery. High blood sugar was observed in all ten patients.
  • Drug levels did not appear to differ by diagnosis (including peritoneal mesothelioma), by extent of surgery or by amount of disease.
• The authors' conclusion: The authors concluded that body surface area can be used to predict oxaliplatin pharmacokinetics in HIPEC. They suggested this was likely due to circulating blood volume, with too little time for the drug to equilibrate. They recommended further study of dosing aimed at a set drug concentration in the abdomen.
• Limitations the authors state:
  • The cohort was small, and toxicity and effectiveness were not prospectively analyzed. For these reasons the authors found it difficult to make clinical recommendations from these data alone.
  • The study did not measure drug levels inside tumors. It used abdominal fluid concentration as a stand-in.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Colon cancer, Mesothelioma, Peritoneal mesothelioma.

Medical terms in this study, explained in our Lexicon: Chemotherapy, HIPEC, Statistical Significance.

Related studies

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• Severe electrolyte disturbances after hyperthermic intraperitoneal chemotherapy: oxaliplatin versus mitomycin C — N.M. Rueth, S.E. Murray, et al. (2011)
• Preoperative Thrombocytosis Predicts Shortened Survival in Patients with Malignant Peritoneal Mesothelioma Undergoing Operative Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy — Y.C. Li, T. Khashab, et al. (2017)
• Is Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy Justified for Biphasic Variants of Peritoneal Mesothelioma? Outcomes from the Peritoneal Surface Oncology Group International Registry — K.I. Votanopoulos, P. Sugarbaker, et al. (2018)
• Quality of life after cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy: a prospective study of 216 patients — G. Passot, N. Bakrin, et al. (2014)
• What made hyperthermic intraperitoneal chemotherapy an effective curative treatment for peritoneal surface malignancy: A 25-year experience with 1,125 procedures — G. Passot, D. Vaudoyer, et al. (2016)

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