Randomized trial of intravenous versus bidirectional chemotherapy after cytoreductive surgery for malignant peritoneal mesothelioma

Our plain-English summary of Randomized trial of intravenous versus bidirectional chemotherapy after cytoreductive surgery for malignant peritoneal mesothelioma, by P.H. Sugarbaker (International Journal of Surgery Protocols, 2023).

The study

• Author: P.H. Sugarbaker
• Journal: International Journal of Surgery Protocols
• Published: 2023;27(3):108-117
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Malignant peritoneal mesothelioma (MPM) is a rare disease that progresses within the peritoneal cavity and only disseminates to systemic sites in the terminal months of the disease. For this malignancy, there are several regimens of chemotherapy that have been accepted as standard, principally intraperitoneal chemotherapy (IPC) and intravenous chemotherapy (IVC); however, there is no standardized method of treatment. Selected patients with MPM who are amenable to cytoreductive surgery (CRS) and are fit for surgery typically undergo resection with hyperthermic intraperitoneal chemotherapy (HIPEC). Though individual toxicity and efficacy studies of IPC plus IVC (bidirectional) and IVC chemotherapy for MPM have been conducted, a prospective randomized clinical trial has not been performed for this disease.

Materials And Methods: The study objective is to compare the efficacy and toxicity of normothermic bidirectional (IPC/IVC) chemotherapy versus IVC after CRS and HIPEC for epithelial MPM. The patient population are those individuals undergoing CRS for MPM. Exclusion criteria include previous therapy form mesothelioma. The study design is a randomized, nonblinded, phase II clinical trial comparing multicycle IVC with cisplatin (CDDP) and pemetrexed (PMTX) versus multicycle bidirectional chemotherapy with IVC CDDP and IPC PMTX after optimal CRS and HIPEC with CDDP and doxorubicin. The primary endpoint is 2-year disease-free survival. The secondary endpoint is 30-day post-treatment morbidity. The primary objective is to compare the 2-year rates of disease-free survival in the two treatment arms. The secondary objective is to compare the toxicity of each treatment.

Dissemination: The prospective randomized trial provides not only a standardized approach to treatment but also a path forward to optimize the survival of patients with MPM. In addition, any increase or decrease in the adverse events associated with PMTX administered as IPC will be demonstrated. Because MPM is a rare disease a multi-institutional implementation of the protocol is required.

Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.

In plain English

This article is a study protocol. It describes a planned clinical trial and reports no patient results. The author proposed a randomized, nonblinded, phase II trial in adults with epithelial-type malignant peritoneal mesothelioma, cancer of the lining of the abdomen. All patients would first have cytoreductive surgery (removal of visible tumor) followed by heated chemotherapy with cisplatin and doxorubicin bathed through the abdomen during the operation (HIPEC). Sixty-four patients were to be randomly assigned to one of two six-cycle regimens. One group would receive cisplatin and pemetrexed both by vein. The other would receive cisplatin by vein and pemetrexed placed directly into the abdomen, which the author called bidirectional chemotherapy. The trial was designed to compare how well the two regimens work and how toxic they are. The author wrote that the trial would provide a standardized approach to treatment and a path toward improving survival. The author also noted that counting recurrences found only by tissue sampling could bias the comparison between the groups.

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: Study protocol for a planned randomized, unblinded, multicenter phase II clinical trial comparing efficacy and toxicity of two chemotherapy regimens after surgery. No results are reported.
• Who was studied: Planned: 64 adult patients (18 or older) with epithelial-type malignant peritoneal mesothelioma undergoing cytoreductive surgery and HIPEC, randomized 1:1 to two arms. No patients had been enrolled.
• Exposure: Treatments, not asbestos. All patients: cytoreductive surgery plus HIPEC with cisplatin and doxorubicin. Arm A: intravenous pemetrexed 500 mg/m2 plus intravenous cisplatin 75 mg/m2 for six cycles every 3 weeks. Arm B: intraperitoneal pemetrexed 500 mg/m2 plus intravenous cisplatin 75 mg/m2 for six cycles every 3 weeks.
• The authors' conclusion: The author stated that the planned trial provides a standardized approach to treatment and a path forward to optimizing survival of patients with malignant peritoneal mesothelioma.
• Limitations the authors state:
  • The author noted that counting recurrences proven by tissue examination, even when imaging shows none, could bias the comparison between arms. If one treatment causes more symptoms that prompt a workup, recurrence would more likely be found in that arm.

Topics

Medical terms in this study, explained in our Lexicon: Chemotherapy, Cytoreductive Surgery, Peritoneal Mesothelioma, Peritoneal Cavity, HIPEC, Clinical Trial, Mesothelioma, Cisplatin.

Related studies

• Conversion to Complete Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Malignant Peritoneal Mesothelioma After Bidirectional Chemotherapy — F. Le Roy, M. Gelli, et al. (2017)
• A 51-Year-Old Woman with Advanced Peritoneal Mesothelioma and Stage 3b Chronic Kidney Disease Treated with Cytoreductive Surgery and Bidirectional Intraperitoneal Cisplatin and Ifosfamide Chemotherapy: A Case Report — M. Alaswad, F. ElKordy, et al. (2023)
• Adjuvant bidirectional chemotherapy with intraperitoneal pemetrexed combined with intravenous Cisplatin for diffuse malignant peritoneal mesothelioma — L. Bijelic, O.A. Stuart, et al. (2012)
• Cytoreductive surgery with selective versus complete parietal peritonectomy followed by hyperthermic intraperitoneal chemotherapy in patients with diffuse malignant peritoneal mesothelioma: a controlled study — D. Baratti, S. Kusamura, et al. (2012)
• Cytoreductive surgery with intraperitoneal hyperthermic chemotherapy for malignant peritoneal mesothelioma: mitomycin versus cisplatin — A.U. Blackham, P. Shen, et al. (2010)
• Phase II Trial of Adjuvant Dendritic Cell Vaccine in Combination with Celecoxib, Interferon-α, and Rintatolimod in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Metastases — R. Ramanathan, H. Choudry, et al. (2021)

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