Oxaliplatin use in pressurized intraperitoneal aerosol chemotherapy (PIPAC) is safe and effective: A multicenter study

Our plain-English summary of Oxaliplatin use in pressurized intraperitoneal aerosol chemotherapy (PIPAC) is safe and effective: A multicenter study, by O. Sgarbura, M. Hübner, M. Alyami, et al (European Journal of Surgical Oncology, 2019).

The study

• Authors: O. Sgarbura, M. Hübner, M. Alyami, C. Eveno, J. Gagnière, B. Pache, M. Pocard, N. Bakrin, F. Quénet
• Journal: European Journal of Surgical Oncology
• Published: 2019;45(12):2386-2391
• Cited by: 58 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new drug delivery method used in patients with peritoneal cancer (PC) of primary or secondary origin. Intraperitoneal use of oxaliplatin raises concerns about toxicity, especially abdominal pain. The objective of this study was to assess the tolerance of PIPAC with oxaliplatin (PIPAC-Ox) in a large cohort of patients and to identify the risk factors for high grade toxicity, discontinuation of treatment and impaired survival.

Material And Methods: This retrospective cohort study included all consecutive patients treated with PIPAC-Ox (92 mg/m2) in five centers specialized in the treatment of PC. The procedure was repeated every 6 weeks. Outcomes of interest were Common Terminology Criteria for Adverse Events (CTCAE), symptoms and survival (Kaplan-Meier). Univariate risk factors were included in a multinominal regression model to control for bias.

Results: Overall, 251 PIPAC-Ox treatments were performed in 101 patients (45 female) having unresectable PC of various origins: 66 colorectal, 15 gastric, 5 ovarian, 3 mesothelioma, 2 pseudomyxoma, 10 other malignancies (biliary, pancreatic, endocrine) respectively. The median PCI was 19 (IQR: 10-28). Postoperative abdominal pain was present in 23 patients. Out of the 9 patients with grade 3 abdominal pain, only 3 needed a change of PIPAC drug. CTCAE 4.0 toxicity grade 4 or higher was encountered in 16(15.9%) patients. The patients had a mean of 2.5 procedures/patient (SD = 1.5). 50 subjects presented with symptom improvement.

Conclusions: Oxaliplatin-based PIPAC appears to be a safe treatment that offers good symptom control and promising survival for patients with advanced peritoneal disease.

Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

In plain English

This multicenter retrospective cohort study looked at the safety of pressurized intraperitoneal aerosol chemotherapy (PIPAC), a way of spraying chemotherapy into the abdomen during a minimally invasive operation, using the drug oxaliplatin (92 mg/m2, repeated at 6-week intervals). It included 101 patients with peritoneal cancer treated at five specialized centers between January 2015 and December 2017. Of these, 66 had colorectal cancer and 3 had peritoneal mesothelioma. The patients received 251 treatments, a mean of 2.5 each. Side effects of grade 3 or higher occurred in 16 patients (15.9%). Grade 3 abdominal pain affected 8.9% of patients, and 3% needed a change of drug. One grade 5 respiratory toxicity was recorded in a patient with a preexisting respiratory condition. Half the patients (49.5%) noted symptom improvement, and overall survival for the whole group was 62% at 30 months. A body mass index below 20 was linked to poorer survival in univariate analysis, but no factor was statistically significant in the multivariate analysis. The authors concluded that the treatment appears feasible and safe. They noted that the study was retrospective, had a limited sample and mixed indications, and had no control group.

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: multicenter retrospective cohort study of all consecutive patients treated with oxaliplatin PIPAC
• Who was studied: 101 patients (56 male, 45 female) with peritoneal cancer treated at five centers between January 2015 and December 2017: 66 colorectal, 15 gastric, 5 ovarian, 3 peritoneal mesothelioma, 2 pseudomyxoma and 10 other cancers; median peritoneal cancer index 19 at the start of treatment
• Exposure: Oxaliplatin given as a pressurized aerosol into the abdomen (PIPAC) at 92 mg/m2 body surface, repeated at 6-week intervals. This is a chemotherapy treatment, not an asbestos exposure.
• Main results:
  • The 101 patients had 251 procedures in total, a mean of 2.5 per patient (plus or minus 1.5). 64.3% had at least 2 procedures and 47.5% had at least 3.
  • 48 patients had some toxicity (grade 1 to 5), with 55 adverse events in total. Grade 3 toxicities occurred in 14 cases (13.9%). Grade 4 and grade 5 events were each under 1%.
  • CTCAE grade 3 or higher toxicity occurred in 16 patients (15.9%)
  • Abdominal pain occurred in 22.8% of all patients. 8.9% of patients had grade 3 pain, and 3% required a change of PIPAC drug.
  • Grade 3 and 4 surgical complications occurred in 4 patients (two hematomas, two surgical site infections). One grade 5 respiratory toxicity was recorded in a patient with a preexisting respiratory condition.
  • 50 patients (49.5%) noted improvement of symptoms during PIPAC treatment
  • Median follow-up after the first PIPAC was 5 months. Median overall survival from the first PIPAC was not reached. Overall survival at 30 months was 62% for the entire group and also for the colorectal patients.
  • No studied factor was related to grade 3 or higher complications. Age over 65 was at the threshold of significance for severe abdominal pain in logistic regression and was significantly related to abdominal pain in linear regression.
  • No prognostic factors were found for stopping treatment early (fewer than 3 PIPAC)
  • In univariate analysis, a BMI below 20 was the only prognostic factor for impaired overall survival. No factor was statistically significant in the multivariate analysis, and Cox regression found no significant survival differences.
• The authors' conclusion: The authors concluded that PIPAC with oxaliplatin 92 mg/m2 appears to be a feasible and safe treatment alternative for patients with advanced peritoneal cancer. They said it offered symptom improvement in half of patients, that short-term survival data were favorable, and that comparative trials are needed to define its indications.
• Limitations the authors state:
  • Retrospective design, limited patient sample, heterogeneous indications and no control group
  • Pain management differed between centers, with some routinely giving opioids, which may interfere with the results
  • Quality of life data were not available for all patients
  • Very few prognostic factors could be identified, probably because the patients were heterogeneous
  • Non-colorectal cancer types were scarcely represented, so their results should not be extrapolated. The survival data are not definitive without randomized controlled trials.

Topics

Medical terms in this study, explained in our Lexicon: Chemotherapy, Cohort Study, Unresectable, Mesothelioma.

Related studies

• Quality of life of patients with end-stage peritoneal metastasis treated with Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) — K. Odendahl, W. Solass, et al. (2015)
• Multicenter comprehensive methodological and technical analysis of 832 pressurized intraperitoneal aerosol chemotherapy (PIPAC) interventions performed in 349 patients for peritoneal carcinomatosis treatment: An international survey study — M. Nowacki, M. Alyami, et al. (2018)
• Multicentric initial experience with the use of the pressurized intraperitoneal aerosol chemotherapy (PIPAC) in the management of unresectable peritoneal carcinomatosis — M. Alyami, J. Gagniere, et al. (2017)
• Unresectable peritoneal metastasis treated by pressurized intraperitoneal aerosol chemotherapy (PIPAC) leading to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy — M. Alyami, F. Mercier, et al. (2021)
• Pressurised intraperitoneal aerosol chemotherapy: rationale, evidence, and potential indications — M. Alyami, M. Hübner, et al. (2019)
• Body surface area predicts plasma oxaliplatin and pharmacokinetic advantage in hyperthermic intraoperative intraperitoneal chemotherapy — J.C. Leinwand, G.E. Bates, et al. (2013)

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