Severe electrolyte disturbances after hyperthermic intraperitoneal chemotherapy: oxaliplatin versus mitomycin C

Our plain-English summary of Severe electrolyte disturbances after hyperthermic intraperitoneal chemotherapy: oxaliplatin versus mitomycin C, by N.M. Rueth, S.E. Murray, S.J. Huddleston, et al (Annals of Surgical Oncology, 2011).

The study

• Authors: N.M. Rueth, S.E. Murray, S.J. Huddleston, A.M. Abbott, E.W. Greeno, M.N. Kirstein, T.M. Tuttle
• Journal: Annals of Surgical Oncology
• Published: 2011;18(1):174-80
• Cited by: 29 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Oxaliplatin (OX) is increasingly used for hyperthermic intraperitoneal chemotherapy (HIPC) for patients with peritoneal metastases. Our aim was to review electrolyte disturbances and complications after HIPC with oxaliplatin (OX) versus mitomycin C (MMC).

Materials And Methods: We included patients enrolled in single-institution prospective clinical trials who underwent cytoreductive surgery and HIPC with MMC or OX. We reviewed patient demographics, pathology, perioperative course, HIPC administration, and postoperative electrolyte disturbances. Measured postoperative sodium values were corrected for systemic hyperglycemia using the formula: (measured Na(+)) × [(glucose - 100/100) × 1.6].

Results: From January 2002 to April 2009 we performed 80 HIPC procedures. A total of 60 patients (75%) received MMC (dose range 12.5-50 mg/m(2)) carried in lactated ringers solution. There were 20 patients (25%) who received OX (dose range 300 × 400 mg/m(2)) carried in 5% dextrose solution. For patients receiving HIPC with OX, electrolyte disturbances were the most common complication. Compared with MMC, patients receiving OX had significant 24-h postoperative uncorrected hyponatremia (P < 0.001), corrected hyponatremia (P < 0.001), hyperglycemia (P < 0.001), and metabolic acidosis (P < 0.001). In the OX group, corrected (mean 130.5) and uncorrected (mean 127.4) sodium levels were significantly lower than preoperatively (mean 139.9, P < 0.001). The overall nonelectrolyte complication rate was 56.2%. (MMC n = 33, 55.0%; OX n = 12, 60%); the 30-day mortality rate was 0% in both groups.

Conclusions: Compared with MMC, HIPC with OX was associated with significant but predictable electrolyte disturbances; however, these electrolyte disturbances were not associated with higher overall complication rates. Close monitoring with early correction is imperative to maximize perioperative care. Further studies are needed to provide mechanistic insight.

In plain English

The authors reviewed 80 patients treated in their own University of Minnesota clinical trials from January 2002 to April 2009. All had surgery to remove cancer from the abdominal lining, from gastrointestinal cancers or peritoneal mesothelioma, followed by heated chemotherapy circulated through the abdomen (HIPC). Sixty received mitomycin C in lactated Ringer's solution; twenty received oxaliplatin in 5% dextrose solution. Most cancers began in the appendix or colon; five mitomycin C patients had mesothelioma. The article does not discuss asbestos. In the 24 hours after surgery, the oxaliplatin group had significantly lower sodium, higher blood sugar and more metabolic acidosis than the mitomycin C group. Ninety percent of oxaliplatin patients developed low sodium. One developed brain swelling linked to low sodium; her sodium normalized within 48 hours without lasting neurological effects. Non-electrolyte complications occurred in 55.0% of mitomycin C patients and 60.0% of oxaliplatin patients. No patient in either group died within 30 days. The authors concluded these disturbances were not associated with higher overall complication rates. They noted the groups came from separate trials and that oxaliplatin patients had no long-term follow-up yet.

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: Retrospective review of patients enrolled in single-institution prospective clinical trials: phase II trials for mitomycin C and a separate phase I trial for oxaliplatin.
• Who was studied: 80 patients at the University of Minnesota who had cytoreductive surgery by a single surgeon plus HIPC, January 2002 to April 2009: 60 received mitomycin C and 20 received oxaliplatin. Patients had primary gastrointestinal disease or peritoneal mesothelioma; mesothelioma accounted for 5 patients (8.3%), all in the mitomycin C group. Patients with gynecologic cancers or spread outside the peritoneal cavity were excluded.
• Exposure: Heated intraperitoneal chemotherapy (41 to 42 degrees C) with mitomycin C at 12.5 to 50 mg/m2 in lactated Ringer's solution, perfused for 60 or 90 minutes, or oxaliplatin at 300 to 400 mg/m2 in 5% dextrose solution, perfused for 30 minutes. No asbestos exposure is studied.
• Main results:
  • In the 24 hours after surgery, compared with the mitomycin C group, the oxaliplatin group had significant uncorrected and corrected hyponatremia, hyperglycemia and metabolic acidosis, each with p less than 0.001. Mean minimum uncorrected sodium was 135.6 mmol/l in the mitomycin C group and 127.4 in the oxaliplatin group. Mean minimum corrected sodium was 136.6 and 130.5. Mean maximum glucose was 162.6 and 288.1 mg/dl. Mean minimum bicarbonate was 24.3 and 20.4 mmol/l.
  • Low magnesium was similar in both groups.
  • 90% of oxaliplatin patients developed hyponatremia. Of the 18 with significant hyponatremia, sodium returned to normal within 72 hours for most; 2 had persistent, asymptomatic hyponatremia.
  • Within the oxaliplatin group, only blood sugar varied with dose: patients given 400 mg/m2 had significantly higher glucose than those given 300 mg/m2 (P = 0.01). The authors found no significant association between dose and the severity of the other electrolyte disturbances.
  • One oxaliplatin patient (dose 400 mg/m2) developed cerebral edema related to hyponatremia, with a minimum sodium of 119 mmol/l. She was treated with hypertonic saline, and her serum sodium normalized within 48 hours without neurologic sequelae.
  • Overall, 45 of 80 patients (56.2%) had 96 non-electrolyte complications: 33 of 60 (55.0%) in the mitomycin C group and 12 of 20 (60.0%) in the oxaliplatin group. The authors reported overall complication rates did not differ between the groups. Reoperation rates were 33.3% (mitomycin C) and 30.0% (oxaliplatin).
  • 30-day mortality was 0% in both groups.
• The authors' conclusion: The authors concluded that, compared with mitomycin C, HIPC with oxaliplatin was associated with significant but predictable electrolyte disturbances. In their data, these disturbances were not associated with higher overall complication rates. They called for close monitoring with early correction, and for longer follow-up to judge survival.
• Limitations the authors state:
  • Retrospective review of patients from separate trials, so patient and treatment variables were set by the different trial protocols and could not be controlled.
  • No long-term follow-up data for the oxaliplatin trial patients, as enrollment had just been completed.

Topics

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

Medical terms in this study, explained in our Lexicon: HIPEC, Mitomycin C, Clinical Trial, Cytoreductive Surgery, Pathology.

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• Body surface area predicts plasma oxaliplatin and pharmacokinetic advantage in hyperthermic intraoperative intraperitoneal chemotherapy — J.C. Leinwand, G.E. Bates, et al. (2013)
• Quality of life after cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy: a prospective study of 216 patients — G. Passot, N. Bakrin, et al. (2014)
• Impact of Combination Chemotherapy in Peritoneal Mesothelioma Hyperthermic Intraperitoneal Chemotherapy (HIPEC): The RENAPE Study — B. Malgras, E. Gayat, et al. (2018)
• Utility of Chemoresponse Assay in Patients Undergoing Cytoreductive Surgery Plus Hyperthermic Intraperitoneal Chemotherapy — S. Bhagwandin, S. Naffouje, et al. (2015)

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