Treatment of primary peritoneal mesothelioma by continuous hyperthermic peritoneal perfusion (CHPP)

Our plain-English summary of Treatment of primary peritoneal mesothelioma by continuous hyperthermic peritoneal perfusion (CHPP), by B.J. Park, H.R. Alexander, S.K. Libutti, et al (Annals of Surgical Oncology, 1999).

The study

• Authors: B.J. Park, H.R. Alexander, S.K. Libutti, P. Wu, D. Royalty, K.C. Kranda, D.L. Bartlett
• Journal: Annals of Surgical Oncology
• Published: 1999;6(6):582-90
• Cited by: 129 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Primary peritoneal mesothelioma is a locally aggressive disease that is difficult to treat or even palliate. Continuous hyperthermic peritoneal perfusion (CHPP) with cisplatin (CDDP) allows uniform, high regional delivery of chemotherapeutics and hyperthermia to the peritoneal surface for the treatment of peritoneal tumors. This article summarizes the results of 18 patients with peritoneal mesothelioma treated with CHPP.

Methods: From June 1993 through April 1998, 18 patients with primary peritoneal mesothelioma (13 male, 5 female; median age, 51 years) underwent surgical exploration and tumor debulking followed by a 90-minute CHPP with CDDP and hyperthermia as part of three consecutive phase I trials conducted at the National Cancer Institute. Seventeen of 18 patients had malignant peritoneal mesothelioma, 13 with associated ascites. One patient had a symptomatic, multiply recurrent, benign, cystic peritoneal mesothelioma. Three patients who had a recurrence after a prolonged progression-free interval (>6 months) after CHPP underwent re-treatment. CHPP parameters included median cisplatin dose of 530 mg (range, 187-816), perfusate volume 6.0 liter (range, 4-9), flow 1.5 liter/min (range, 1-2), intraperitoneal temperature 41 degrees C (range, 38.7-43.2), and central temperature 38.6 degrees C (range, 36.8-39.7).

Results: Median follow-up after CHPP is 19 months (range, 2-56) with no operative or treatment-related mortality. Overall operative morbidity was 24% and included two patients with superficial wound infection and one patient each with atrial fibrillation, pancreatitis, fascial dehiscence, ileus, line sepsis, and clostridium difficile colitis. The major treatment-related toxicity was systemic renal toxicity at doses above what was defined as the maximum tolerated dose of cisplatin. Nine of 10 patients had resolution of their ascites postoperatively. Three patients who developed recurrent ascites (27, 22, and 10 months after initial treatment) were re-treated and had resolution of their ascites with ongoing responses at 24, 6, and 4 months after the second perfusion. The median progression-free survival was 26 months, and the overall 2-year survival was 80%. The median overall survival has not been reached.

Conclusions: CHPP with cisplatin can be performed safely with no mortality and minimal morbidity. In selected patients, successful palliation in the abdomen and long-term survival, compared with historical controls, can be achieved with aggressive surgical debulking and CHPP. Re-treatment after initial response can result in a second long-term response.

In plain English

This report described 18 patients with primary peritoneal mesothelioma (17 malignant, one benign cystic) treated at the National Cancer Institute in three phase I trials, 1993 to 1998. Each had as much tumor removed as possible, then a 90-minute heated cisplatin wash of the abdomen. Three were treated twice, giving 21 treatments. The article does not discuss asbestos. No patient died from surgery; complications followed 5 of 21 operations (the reported 24%). Five patients given cisplatin above the maximum tolerated dose had a grade 3 or 4 creatinine rise (kidney toxicity); one needed hemodialysis. Ascites (abdominal fluid) cleared in 9 of the 10 who had it. Median progression-free survival across the 21 treatments was 26 months; for the 18 patients, estimated 2-year survival was 80% and median overall survival was not reached, at median follow-up of 19 months. Three patients left with bulky tumor died of disease. The authors concluded it was safe and could give selected patients palliation and long survival. They said that without a control group, no survival advantage over surgery alone could be concluded.

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: Case series of patients treated within three consecutive phase I clinical trials, with no control group. Survival was estimated with Kaplan-Meier curves.
• Who was studied: 18 patients with primary peritoneal mesothelioma referred to the Surgery Branch of the National Cancer Institute (Bethesda, Maryland), June 1993 to April 1998. There were 13 men and 5 women. 17 had malignant and 1 had benign cystic peritoneal mesothelioma. Three patients were treated twice, for 21 treatments in total.
• Exposure: This is a treatment study, and asbestos or other causes of the disease are not discussed. Patients had surgical tumor debulking followed by a 90-minute continuous hyperthermic peritoneal perfusion with cisplatin (median dose 530 mg). Some also received tumor necrosis factor, or paclitaxel and 5-FU.
• Main results:
  • No patients died around the time of surgery.
  • Overall operative morbidity was 24%. Table 2 lists complications after 5 of the 21 procedures, which matches this figure; it is not 24% of the 18 patients.
  • The main toxicity was kidney impairment. Five patients, all treated above the maximum tolerated cisplatin dose, had a grade 3 or 4 rise in creatinine.
  • One patient needed hemodialysis. The others recovered with supportive care.
  • Ascites resolved after therapy in 9 of the 10 patients who had ascites.
  • Three patients developed recurrent ascites 27, 22 and 10 months after the first treatment and were treated again. Their ascites resolved, with ongoing responses at 24, 6 and 4 months after the second perfusion.
  • Median progression-free survival was 26 months. This was calculated across the 21 CHPP treatments, including the repeat treatments in three patients.
  • For the 18 patients, median overall survival had not been reached. The 2-year survival rate was 80% (a Kaplan-Meier estimate).
  • Median follow-up was 19 months (range 2 to 56).
  • The three patients left with bulky residual tumor after surgery died of their disease.
  • Four patients debulked to minimal residual disease were free of symptoms and of detectable disease at 29, 31, 34 and 35 months of follow-up.
• The authors' conclusion: The authors concluded that CHPP with cisplatin can be performed safely with no mortality and minimal morbidity. They said that in selected patients, aggressive surgical debulking plus CHPP can achieve palliation in the abdomen and long-term survival compared with historical controls.
• Limitations the authors state:
  • There was no control group, and long-term spontaneous remissions have been reported in peritoneal mesothelioma. The authors said this made conclusions about a survival advantage over surgical debulking alone impossible.
  • The authors stated that no conclusions can be drawn about how the different drugs compare with one another in activity and effectiveness.

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: Peritoneal Mesothelioma, Cisplatin, Ascites, Progression-Free Survival, Median Overall Survival.

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• Malignant peritoneal mesothelioma treated by continuous hyperthermic peritoneal perfusion chemotherapy — E. de Bree, M. Christodoulakis, et al. (2000)
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