Lay Summary: Heated intraperitoneal chemotherapy remains controversial despite a consensus statement.
Gastrointestinal and gynecologic malignancies frequently disseminate to the peritoneal surfaces. Prevention or adequate treatment of disease at this anatomical site would improve the survival of patients if dissemination did not occur elsewhere in the body. For patients with distant metastases, eradication of cancer on abdominal and pelvic surfaces would result in a quality of life advantage because intestinal obstructions would occur much less frequently. One method pioneered by Dr. Sugarbaker is to treat the peritoneal surface component of these malignancies is heated intraoperative intraperitoneal chemotherapy. Heat synergizes the cytotoxic effects of chemotherapy. In addition, heat increases the penetration of chemotherapy solution into cancer nodules. To improve penetration of tumor nodules by chemotherapy, the size of tumor nodules is maximally cytoreduced before the heated chemotherapy treatments. The literature contains nine international studies, an international registry of 506 patients from 28 institutions, and one single-institution Phase III randomized study with 105 patients. The nine studies showed a three-year survival rate of 25% to 58%, and a five-year survival rate of 11% to 32%.
The registry showed an overall median survival rate of 19.2 months, with a three-year survival rate of 39% and a five-year survival rate of 19%. In the Phase III study, the median survival rate for the chemotherapy-arm was 12.6 months vs 22.3 months for the patients in the HIPEC arm. A consensus statement signed by the Peritoneal Surface Malignancies Group (PSMG), a collection of 72 national and international surgical oncologists from 14 countries, concluded that delivering heated chemotherapy into the peritoneal cavity following cytoreductive surgery may significantly increase the life expectancy of some Stage IV colorectal cancer patients.However this recommendation was made by a selected groups of the proponents of this therapy and it has not been widely accepted.
The technique is considered by some to be experimental, but some experts disagree. quote from the conclusion for a review in The Oncologist in 2009: ” In combination with surgery, it remains a sensible theoretical option for patients with this disease that can be delivered without great additional morbidity. Although initial investigators focused on recurrent disease, it seems sensible to incorporate it earlier, at the time of front-line treatment or for consolidation. Future progress will be hastened by national and international collaboration in the performance of large, randomized, controlled trials of HIPEC at each of the natural history time points of the disease. “
The other unresolved issue is that in the absence of comparison between HIPEC and newer systemic chemotherapy regimens, such as Folfox/Avastin, we do not know whether the IV chemotherapy is not better, or at least equivalent to the much more toxic HIPEC. This is due to the fact that the randomized trials compared to HIPEC with older systemic chemotherapy regimen i.e. 5FU/leucovorin. The current newer regimens which include Oxaliplatin and Irinotecan show similar survival advantage as HIPEC. Four randomised trials are ongoing and their results are eagerly awaited. In the meantime, Turage et al published a consensus guideline supporting HIPEC.
Canadian Agency for Drugs and Technologies in Health (CADTH). Hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis: Clinical effectiveness and guidelines. Rapid Response Report: Summary of Abstracts. Ottawa, ON: CADTH; November 1, 2016.
Watson, Paul Advanced Colorectal Cancer: Consensus Group Recommends Heated Chemotherapy after Surgery, but Other Experts Disagree, Citing Need for Phase III Data.
Oncology Times. 29(2):24,27-29, January 25, 2007.
O. Anthony Stuart, BS, Arvil D. Stephens, BS, Laura Welch, MD and Paul H. Sugarbaker, MD Safety Monitoring of the Coliseum Technique for Heated Intraoperative Intraperitoneal Chemotherapy With Mitomycin C Annals of Surgical Oncology 9:186-191 (2002)
NHS Guidelines – http://www.nice.org.uk/pdf/ip/IPG116guidance.pdf
Esquivel, Jesus (2010). “Technology of Hyperthermic Intraperitoneal Chemotherapy in the United States, Europe, China, Japan and Korea”. In Vincent T. DeVita Jr., Theodore S. Lawrence, Steven A. Rosenberg. Cancer: Principles & Practice of Oncology—Annual Advances in Oncology, Volume 1. Lippincott Williams & Wilkins. pp. 188–193.
Mulier S, Claes JP, Dierieck V, Amiel JO, Pahaut JP, Marcelis L, Bastin F, Vanderbeeken D, Finet C, Cran S, Velu T. Survival benefit of adding Hyperthermic IntraPeritoneal Chemotherapy (HIPEC) at the different time-points of treatment of ovarian cancer: review of evidence. Curr Pharm Des. 2012;18(25):3793-803.
K. Turaga, et al, Consensus Guidelines from The American Society of Peritoneal Surface Malignancies on Standardizing the Delivery of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Colorectal Cancer Patients in the United StatesAnnals of Surgical OncologyMay 2014, Volume 21, Issue 5, pp 1501–1505