Adjuvant bidirectional chemotherapy with intraperitoneal pemetrexed combined with intravenous Cisplatin for diffuse malignant peritoneal mesothelioma

Our plain-English summary of Adjuvant bidirectional chemotherapy with intraperitoneal pemetrexed combined with intravenous Cisplatin for diffuse malignant peritoneal mesothelioma, by L. Bijelic, O.A. Stuart, P. Sugarbaker (Gastroenterology Research and Practice, 2012).

The study

• Authors: L. Bijelic, O.A. Stuart, P. Sugarbaker
• Journal: Gastroenterology Research and Practice
• Published: 2012;2012:890450
• Cited by: 24 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Cytoreductive surgery (CRS) with heated intraoperative intraperitoneal chemotherapy (HIPEC) has emerged as optimal treatment for diffuse malignant peritoneal mesothelioma (DMPM) showing median survivals of 36-92 months. However, recurrences occur frequently even in patients undergoing optimal cytreduction and are often confined to the abdomen. We initiated a Phase II study of adjuvant intraperitoneal pemetrexed combined with intravenous cisplatin for patients undergoing CRS and HIPEC for DMPM. The treatment consisted of pemetrexed 500 mg/m(2) intraperitoneally and cisplatin 50 mg/m(2) intravenously given simultaneously on day 1 of every 21 day cycle for 6 cycles. The primary endpoint of the study was treatment related toxicity. From July 2007 until July 2009 ten patients were enrolled. Nine of 10 completed all 6 cycles of adjuvant treatment per protocol. The most common toxicities were fatigue, nausea and abdominal pain grade 1 or 2. There was one grade 3 toxicity consisting of a catheter infection. The median survival for all 10 patients was 33.5 months. Pharmacokinetic analysis of intraperitoneal pemetrexed showed a peritoneal to plasma area under the curve ratio of 70. Our study shows that adjuvant intravenous cisplatin and intraperitoneal pemetrexed can be used following CRS and HIPEC for DMPM with low morbidity.

In plain English

This small single-hospital Phase II study tested chemotherapy after surgery for diffuse malignant peritoneal mesothelioma (cancer of the abdominal lining). The article does not discuss asbestos. Ten patients enrolled from July 2007 to July 2009 after cytoreductive surgery plus heated abdominal chemotherapy (HIPEC). Each was to receive pemetrexed into the abdomen through an implanted port and cisplatin into a vein, every 21 days for 6 cycles. The main goal was measuring side effects. Nine of the 10 completed all 6 cycles without delays. Fatigue, nausea and abdominal pain were the commonest side effects, generally mild. The only grade 3 side effect was a catheter infection; the catheter was removed and that patient received both drugs by vein for one cycle. No treatment-related deaths occurred. In four patients, drug exposure in abdominal fluid was about 70 times that in blood. After a median follow-up of 44 months, 4 patients had no evidence of disease, 2 were alive with disease and 4 had died of disease. Median survival was 33.5 months. The authors concluded the treatment could follow surgery with low morbidity.

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: Single-institution Phase II clinical trial (also called Phase I/II in the text) of adjuvant chemotherapy, with no comparison group; the main endpoint was treatment-related toxicity
• Who was studied: 10 patients (7 male, 3 female; mean age 51, range 23 to 69) with histologically confirmed diffuse malignant peritoneal mesothelioma (8 epithelioid, 2 biphasic) who had cytoreductive surgery and HIPEC at Washington Hospital Center, Washington, DC; enrolled July 2007 to July 2009
• Exposure: Not an asbestos exposure study. The planned treatment was intraperitoneal pemetrexed 500 mg/m2 plus intravenous cisplatin 50 mg/m2, given on day 1 of each 21-day cycle for 6 cycles, after cytoreductive surgery and HIPEC (cisplatin plus doxorubicin). One patient received intravenous pemetrexed for one cycle after a catheter infection. 9 of 10 patients also received early postoperative intraperitoneal paclitaxel.
• Main results:
  • 9 of the 10 patients completed all 6 cycles without treatment delays
  • One patient developed a catheter infection after cycle 3 and needed the catheter removed; this was the only grade 3 toxicity among the 10 patients
  • That patient received intravenous pemetrexed and cisplatin for one cycle, then had a new peritoneal catheter placed and completed cycles 5 and 6 according to protocol
  • The most common toxicities in the 10 patients were fatigue, nausea and abdominal pain, generally mild (grade I to II: fatigue 6, nausea 5, abdominal pain 5, alopecia 2; no neutropenia or thrombocytopenia recorded)
  • No treatment-related deaths and no hospitalizations due to treatment side effects among the 10 patients
  • In 4 patients studied on the first cycle, the peritoneal-fluid-to-plasma area under the curve ratio for pemetrexed was 70
  • After a median follow-up of 44 months, of the 10 patients 4 had no evidence of disease, 2 were alive with disease, and 4 had died of disease
  • Median survival for all 10 patients was 33.5 months
  • Among the 6 living patients, with a median follow-up of 50 months, no long-term symptoms of peritoneal sclerosis were observed
  • A planned dose escalation of intraperitoneal pemetrexed was not done because, in the authors' judgment, the fatigue patients experienced did not suggest it was possible
• The authors' conclusion: The authors concluded that adjuvant combined intravenous and intraperitoneal chemotherapy can be given to patients with peritoneal mesothelioma after CRS and HIPEC with low morbidity

Topics

Medical terms in this study, explained in our Lexicon: Chemotherapy, Pemetrexed (Alimta), Cisplatin, Peritoneal Mesothelioma, Cytoreductive Surgery, HIPEC, Median Overall Survival.

Related studies

• Adjuvant bidirectional chemotherapy using an intraperitoneal port — P.H. Sugarbaker, L. Bijelic (2012)
• 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)
• Randomized trial of intravenous versus bidirectional chemotherapy after cytoreductive surgery for malignant peritoneal mesothelioma — P.H. Sugarbaker (2023)
• Bidirectional Intraoperative Chemotherapy Using Cisplatin and Ifosfamide for Intraperitoneal Mesothelioma in Severe Renal Impairment: A Case Report — R. Almesned, A.Z. Azzam, et al. (2023)
• Conversion to Complete Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Malignant Peritoneal Mesothelioma After Bidirectional Chemotherapy — F. Le Roy, M. Gelli, et al. (2017)
• 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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