Unusually favorable outcome of 6 consecutive patients with diffuse malignant peritoneal mesothelioma treated with repeated doses of intraperitoneal paclitaxel. A case series

Our plain-English summary of Unusually favorable outcome of 6 consecutive patients with diffuse malignant peritoneal mesothelioma treated with repeated doses of intraperitoneal paclitaxel. A case series, by P.H. Sugarbaker, O.A. Stuart (Surgical Oncology, 2020).

The study

• Authors: P.H. Sugarbaker, O.A. Stuart
• Journal: Surgical Oncology
• Published: 2020;33:96-99
• Cited by: 11 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Diffuse malignant peritoneal mesothelioma (DMPM) is a disease in transition. Two decades ago this cancer had a median survival of 1 year. Recent reports in selected patients show a 5-year survival of 70% and median survival not reached at 10 years.

Methods: Consecutive patients with a biopsy-confirmed diagnosis of DMPM, epithelial type, were treated by a consistent treatment plan. Cytoreductive surgery using peritonectomy procedures was always the first intervention. In the operating theater after all resections were complete but prior to intestinal reconstruction, hyperthermic intraperitoneal chemotherapy (HIPEC) using 2 cytotoxic agents was given. An intraperitoneal port was placed for normothermic intraperitoneal chemotherapy (NIPEC). Prospective data regarding pharmacokinetics, survival and adverse events were accumulated.

Results: Six consecutive patients were treated. Three to 6 one-week long cycles of normothermic intraperitoneal paclitaxel were administered through an intraperitoneal port. No systemic chemotherapy was given. Pharmacokinetic studies were performed on 5 patients. Four patients are free of disease at 8, 13, 18, and 19 years and two patients died of disease 15 years after definitive treatment. Three of 6 patients had a grade III/IV adverse event related to intraperitoneal chemotherapy administration through a port.

Conclusions: The small number of patients treated with repeated doses of intraperitoneal paclitaxel cause these data to be interpreted with caution. However, the long-term benefit and favorable pharmacology of these patients suggests the need for further study. Adverse events from this intraperitoneal port were recorded in half of the patients.

Copyright © 2020 Elsevier Ltd. All rights reserved.

In plain English

This was a case series of six consecutive patients with diffuse malignant peritoneal mesothelioma, epithelial type, treated at Washington Hospital Center from 2000 through 2011. The article did not discuss asbestos exposure. All patients had cytoreductive surgery, then heated chemotherapy with cisplatin and doxorubicin given into the abdomen during the operation, then paclitaxel given into the abdomen on days 1 to 5 after surgery. More 5-day cycles of paclitaxel followed through an abdominal port, with a goal of 6 cycles. Two patients completed 3 cycles, one completed 5, one completed 6, and two completed an unknown number above 3. Four of the 6 patients were free of disease at 8, 13, 18 and 19 years, and two died of disease 15 years after treatment. Three of the 6 had a grade III/IV adverse event: an inverted and then infected port, an intense allergic reaction, and a small bowel perforation. In 5 patients, drug measurements showed 355 times more paclitaxel exposure of the abdominal lining than with intravenous exposure. The study had no randomization. The authors concluded that the small numbers call for caution, but that the results suggest the need for further study.

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. Clinical and drug-level data were recorded prospectively and reviewed retrospectively for publication.
• Who was studied: 6 consecutive patients with biopsy-confirmed diffuse malignant peritoneal mesothelioma, epithelial type, treated at Washington Hospital Center (Washington, DC) from 2000 through 2011. There were 4 males. Ages were 23 to 61, median 53.
• Exposure: Asbestos exposure was not reported. The study examined treatment: cytoreductive surgery; heated intraoperative chemotherapy (HIPEC) with cisplatin 50 mg/m2 and doxorubicin 15 mg/m2 for 90 minutes; paclitaxel into the abdomen on postoperative days 1 to 5 at 20 mg/m2; then 5-day cycles of normothermic intraperitoneal paclitaxel through a port. The port dose started at 20 mg/m2/day, rose 5 mg/m2/day each cycle to a maximum of 40 mg/m2/day, with a goal of 6 cycles.
• Main results:
  • Four of the 6 patients had no evidence of disease at follow-up of 8, 13, 18 and 19 years. Two patients died 15 years after cytoreductive surgery; the table lists them as died of disease.
  • Number of port paclitaxel cycles completed: 3 cycles in two patients, 5 in one, 6 in one, and an unknown number (more than 3) in two.
  • Three of 6 patients had a grade III/IV adverse event related to intraperitoneal chemotherapy given through a port.
  • The adverse events were: a port that inverted and, after surgical repair, became infected; an intense allergic response, presumably to paclitaxel, causing profound ascites; and a small bowel perforation after the fifth cycle, which was repaired.
  • In drug-level studies in 5 patients at a paclitaxel dose of 20 mg/m2, 92% of the paclitaxel had passed from the abdominal cavity into the body by 24 hours. Peritoneal surfaces had 355 times the drug exposure compared with intravenous exposure.
• The authors' conclusion: The authors concluded that because so few patients were treated, the data should be interpreted with caution. They stated that the long-term benefit and favorable drug behavior in these patients suggest the need for further study, and that port-related adverse events occurred in half of the patients.
• Limitations the authors state:
  • Only 6 patients, and no randomization.
  • The protocol was stopped early, when a new protocol replaced it after FDA approval of cisplatin and pemetrexed. This limited the number of patients studied.
  • The port-related adverse events reflected the team's early experience with port placement. The authors note that the technique has since changed.

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, Median Survival, Biopsy, Cytoreductive Surgery, HIPEC, Chemotherapy.

Related studies

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• Iterative cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for recurrent or progressive diffuse malignant peritoneal mesothelioma: clinicopathologic characteristics and survival outcome — C. Ihemelandu, L. Bijelic, et al. (2015)
• Multicystic peritoneal mesothelioma: outcomes and patho-biological features in a multi-institutional series treated by cytoreductive surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) — D. Baratti, M. Vaira, et al. (2010)
• Two-Stage Cytoreductive Surgery and Intraperitoneal Chemotherapy for Diffuse Malignant Peritoneal Mesothelioma: Predictors of Overall Survival in an Intention-to-Treat Series — J.C. Leinwand, R.N. Taub, et al. (2020)
• 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)
• Repeat cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for recurrent diffuse malignant peritoneal mesothelioma — Y. Huang, N.A. Alzahrani, et al. (2015)

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