Intraperitoneal therapy for peritoneal tumors: biophysics and clinical evidence

Our plain-English summary of Intraperitoneal therapy for peritoneal tumors: biophysics and clinical evidence, by W.P. Ceelen, M.F. Flessner (Nature Reviews. Clinical Oncology, 2010).

The study

• Authors: W.P. Ceelen, M.F. Flessner
• Journal: Nature Reviews. Clinical Oncology
• Published: 2010;7(2):108-15
• Type of article: Review
• Cited by: 137 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

In patients with tumors confined to the peritoneal cavity, there is established pharmacokinetic and tumor biology-related evidence that intraperitoneal drug administration is advantageous. Three large randomized trials in patients with stage III ovarian cancer who underwent optimal cytoreduction have demonstrated a significant survival benefit when intraperitoneal chemotherapy was added to systemic therapy. Although intraperitoneal therapy is associated with locoregional toxic effects, recent trials suggest that with some modification of the local delivery methods this approach is safe in 80% of patients in an ambulatory setting. Surgical cytoreduction immediately followed by intraoperative hyperthermic intraperitoneal chemoperfusion (HIPEC) ensures intraperitoneal delivery of the drug to all peritoneal surfaces and the advantages of combined hyperthermia to be exploited. An increasing number of centers are initiating this multimodality therapy in ovarian cancer and colorectal cancer. Clearly, intraperitoneal drug delivery is an important adjunct to surgery and systemic chemotherapy in selected patients. The optimal drug, dose and schedule for intraperitoneal delivery, the exact role of added HIPEC compared with cytoreduction alone, and the potential role of HIPEC in ovarian cancer and peritoneal mesothelioma are still undefined. Several randomized controlled trials addressing these uncertainties have been initiated.

In plain English

This article was a review, not a new study. The authors searched the ISI Web of Knowledge for articles published before 1 May 2009 on chemotherapy given directly into the abdominal (peritoneal) cavity. The article does not discuss asbestos exposure. Among the studies reviewed, three large randomized trials in patients with stage III ovarian cancer who had undergone optimal surgical cytoreduction showed a significant survival benefit when platinum-based intraperitoneal chemotherapy was added to systemic therapy. For malignant peritoneal mesothelioma, the authors cited a systematic review of six published series totaling 240 patients treated with surgery plus heated intraperitoneal chemotherapy (HIPEC). That review reported median survival ranging from 34 to 92 months. Reported death rates after surgery with HIPEC ranged from 3 to 8%, and complication rates from 20 to 50%. The authors concluded that intraperitoneal drug delivery has shown efficacy in patients with minimal or microscopic residual tumors confined to the peritoneal cavity. They also concluded that HIPEC in peritoneal mesothelioma is promising but not yet demonstrated in controlled randomized trials. For cytoreduction with HIPEC in colorectal cancer, they noted that the overall quality of the available evidence was rather low.

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: Review of published literature on intraperitoneal chemotherapy, based on a systematic database search plus additional references
• Who was studied: Published articles identified in ISI Web of Knowledge before 1 May 2009, with no language restrictions, plus references from identified papers and books. The reviewed studies covered patients with ovarian, colorectal, appendiceal and gastric cancer and with malignant peritoneal mesothelioma.
• Exposure: No asbestos exposure was studied. The subject was a treatment: cytotoxic drugs given into the peritoneal cavity, either after surgery or as heated intraoperative chemoperfusion (HIPEC).
• Main results:
  • Malignant peritoneal mesothelioma (from a systematic review the authors cited): six published series totaling 240 patients treated with cytoreduction and HIPEC had median survival ranging from 34 to 92 months
  • Stage III ovarian cancer patients who underwent optimal cytoreduction (from three randomized trials the authors cited): survival improved significantly when platinum-based intraperitoneal chemotherapy was added to systemic therapy
  • Peritoneal carcinomatosis from colorectal cancer (from a randomized trial by Verwaal and co-authors that the authors cited): median disease-specific survival was 12.6 months in the control arm and 22.2 months in the cytoreduction with HIPEC arm (P = 0.028)
  • Cytoreduction with HIPEC (from studies the authors cited): documented mortality rates of 3 to 8% and postoperative complication rates of 20 to 50%
• The authors' conclusion: The authors concluded that intraperitoneal drug delivery has demonstrated efficacy in patients with minimal or microscopic residual tumors confined to the peritoneal cavity. They also stated that HIPEC in ovarian cancer and peritoneal mesothelioma is promising but has not been demonstrated in controlled randomized trials.
• Limitations the authors state:
  • The authors noted that the overall quality of the available evidence on cytoreduction and HIPEC in colorectal cancer was rather low
  • The authors noted that some control arms in the ovarian cancer trials used intravenous regimens that were no longer considered standard of care
  • The authors stated that the adverse effects of combined cytoreduction and HIPEC are substantial and that randomized trials are needed

Topics

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

Medical terms in this study, explained in our Lexicon: Peritoneal Cavity, Ovarian Cancer, Cytoreductive Surgery, Chemotherapy, Systemic Therapy, HIPEC, Multimodal Therapy, Colorectal Cancer.

Related studies

• Quality of life after cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy: a prospective study of 216 patients — G. Passot, N. Bakrin, et al. (2014)
• 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)
• The role of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal carcinomatosis: a systematic review including evidence from Japan — T. Kitai (2021)
• Long-term survival outcomes of cytoreductive surgery and perioperative intraperitoneal chemotherapy: Single-institutional experience with 1225 cases — L.S. Kyang, N.A. Alzahrani, et al. (2019)
• Peritonectomy and hyperthermic intraperitoneal chemotherapy: cost analysis and sustainability — P.F. Bagnoli, F.C. Cananzi, et al. (2015)
• Risk of definitive stoma after surgery for peritoneal malignancy in 958 patients: comparative study between complete cytoreductive surgery and maximal tumor debulking — S. Riss, K. Chandrakumaran, et al. (2015)

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