First-line chemotherapy with pemetrexed plus cisplatin for malignant peritoneal mesothelioma

Our plain-English summary of First-line chemotherapy with pemetrexed plus cisplatin for malignant peritoneal mesothelioma, by E. Fujimoto, T. Kijima, K. Kuribayashi, et al (Expert Review of Anticancer Therapy, 2017).

The study

• Authors: E. Fujimoto, T. Kijima, K. Kuribayashi, Y. Negi, S. Kanemura, K. Mikami, H. Doi, K. Kitajima, T. Nakano
• Journal: Expert Review of Anticancer Therapy
• Published: 2017;17(9):865-872
• Cited by: 25 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Mesothelioma of peritoneal origin has wider variation in treatment outcomes than mesothelioma of pleural origin, likely because peritoneal mesothelioma comprises borderline malignant variants and aggressive malignant peritoneal mesothelioma (MPeM). This study retrospectively evaluates the efficacy of first-line systemic pemetrexed and cisplatin chemotherapy in MPeM.

Research Design And Methods: Twenty-four patients with histologically proven MPeM were treated with pemetrexed plus cisplatin as a first-line systemic chemotherapy. The response was evaluated radiologically according to standard Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Twenty-two patients underwent 18F-fluorodeoxyglucose positron emission tomography/(FDG-PET)/computed tomography(CT) at baseline, and 13 were eligible for metabolic assessment.

Results: Two complete responses and 9 partial responses were achieved. Overall response rate and disease control rate were 45.8% and 91.7%, respectively. Median progression-free survival and median overall survival were 11.0 months and 15.8 months, respectively. Wet- type MPeM had significantly longer survival (40.9 months median) than other clinical types (15.5 months) (P = 0.045). The baseline maximum standardized uptake value in 22 patients was 8.93 (range, 2.5-16.77).

Conclusions: Systemic pemetrexed plus cisplatin is active for MPeM. Disparity with the outcome of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) needs to receive more emphasis, since peritoneal mesothelioma has a 5-year survival rate of 50%.

In plain English

This retrospective study reviewed 24 consecutive patients in Japan with malignant peritoneal (abdominal-lining) mesothelioma who had no prior chemotherapy and were unsuitable for aggressive surgery. From March 2007 to July 2015 they received first-line pemetrexed plus cisplatin. Asbestos exposure was documented in 18 of 24: 15 occupational, 3 environmental. On CT scans, 2 had a complete response and 9 a partial response; the objective response rate was 45.8% and disease control rate 91.7%. Median progression-free survival was 11.0 months (95% CI 10.0 to 11.9) and median overall survival 15.8 months (95% CI 14.6 to 17.0). In a univariate analysis, the 7 'wet'-type patients (large fluid build-up without abdominal pain) had median survival of 40.9 months (95% CI 16.8 to 65.0), against 15.5 months (95% CI 8.6 to 22.3) for the other types (P = 0.045). CT responders and those given 5 or more cycles also survived longer. A survival difference by PET-scan response was not statistically significant. No treatment-related deaths occurred. The authors concluded the regimen is active and called for randomized comparisons with surgery plus intraperitoneal chemotherapy.

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: Retrospective study of consecutive patients treated at a single institution
• Who was studied: 24 consecutive chemotherapy-naive patients (16 men, 8 women; median age 66, range 32 to 76) with pathologically proven malignant peritoneal mesothelioma not amenable to aggressive surgery, treated March 2007 to July 2015 at a single institution in Japan (Hyogo College of Medicine)
• Exposure: The treatment studied was intravenous pemetrexed (500 mg/m2 on day 1) plus cisplatin (75 mg/m2 on day 1), repeated every three weeks. Patients' asbestos exposure history was also recorded; no fiber types were named.
• Main results:
  • Asbestos exposure history was documented in 18 of 24 patients (75.0%): 15 (62.5%) occupational and 3 (12.5%) environmental
  • All 24 patients: complete response in 2 (8.3%), partial response in 9 (printed as 37.6%), stable disease in 11 (45.8%); objective response rate 45.8%, disease control rate 91.7%
  • All 24 patients: median progression-free survival 11.0 months (95% CI 10.0 to 11.9); median overall survival 15.8 months (95% CI 14.6 to 17.0)
  • All 24 patients: 1-year, 2-year and 3-year survival rates were 58.3%, 20.8% and 12.5%
  • In the univariate model, wet-type patients (7) had median overall survival of 40.9 months (95% CI 16.8 to 65.0), compared with 15.5 months (95% CI 8.6 to 22.3) for the dry-painful and combined types together (P = 0.045)
  • Radiological (CT) responders had median overall survival of 23.6 months (95% CI 13.3 to 33.9) versus 13.2 months (95% CI 7.2 to 19.3) for non-responders, p = 0.032
  • Of 13 patients assessable by FDG-PET, metabolic responders had median overall survival of 22.3 months (95% CI 13.3 to 36.7) versus 15.8 months (95% CI 8.4 to 23.5) for non-responders; the difference was not statistically significant (p = 0.76)
  • The 13 patients who received 5 or more cycles had median overall survival of 22.3 months (95% CI 13.4 to 31.2), against 9.1 months (95% CI 3.0 to 15.1) for those who received fewer than 5 cycles (P = 0.039)
  • There were no treatment-related deaths. The most common grade 3 or 4 blood-related side effect was neutropenia (29.2%).
• The authors' conclusion: The authors concluded that systemic pemetrexed plus cisplatin is active for malignant peritoneal mesothelioma
• Limitations the authors state:
  • The study was retrospective
  • The authors attributed the non-significant survival difference between metabolic responders and non-responders mainly to the small number of patients
  • No randomized trials exist for this disease. The authors stated that randomized studies comparing surgery plus intraperitoneal chemotherapy with pemetrexed plus cisplatin are required.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

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

Related studies

• A Phase II Trial of First-Line Combination Chemotherapy With Cisplatin, Pemetrexed, and Nivolumab for Unresectable Malignant Pleural Mesothelioma: A Study Protocol — N. Fujimoto, K. Aoe, et al. (2018)
• Carboplatin plus pemetrexed as first-line treatment of patients with malignant pleural mesothelioma: a phase II study — N. Katirtzoglou, I. Gkiozos, et al. (2010)
• Comparison of cisplatin plus pemetrexed and cisplatin plus gemcitabine for the treatment of malignant pleural mesothelioma in Japanese patients — T. Shukuya, T. Takahashi, et al. (2014)
• Tumour Treating Fields in combination with pemetrexed and cisplatin or carboplatin as first-line treatment for unresectable malignant pleural mesothelioma (STELLAR): a multicentre, single-arm phase 2 trial — G.L. Ceresoli, J.G. Aerts, et al. (2019)
• Correlation between TS, MTHFR, and ERCC1 gene polymorphisms and the efficacy of platinum in combination with pemetrexed first-line chemotherapy in mesothelioma patients — T. Powrózek, D.M. Kowalski, et al. (2014)
• Trimodality strategy for treating malignant pleural mesothelioma: results of a feasibility study of induction pemetrexed plus cisplatin followed by extrapleural pneumonectomy and postoperative hemithoracic radiation (Japan Mesothelioma Interest Group 0601 Trial) — S. Hasegawa, M. Okada, et al. (2016)

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