Long progression-free survival by pemetrexed continuation maintenance therapy following cisplatin-based chemotherapy in malignant pleural mesothelioma

Our plain-English summary of Long progression-free survival by pemetrexed continuation maintenance therapy following cisplatin-based chemotherapy in malignant pleural mesothelioma, by T. Takeda, H. Itano, S. Fukita, et al (Internal Medicine, 2014).

The study

• Authors: T. Takeda, H. Itano, S. Fukita, M. Saitoh, S. Takeda
• Journal: Internal Medicine
• Published: 2014;53(20):2347-51
• Type of article: Case report
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma (MPM) is associated with a poor prognosis. The combination of cisplatin and pemetrexed has been established as a standard chemotherapy that confers a survival benefit. Because the regimen is sometimes hampered by the renal toxicity of cisplatin and no second-line chemotherapy has yet been established, the strategy of administering a higher total dose of pemetrexed to optimize the regimen could be promising. We herein describe the case of a 69-year-old man with MPM who underwent five cycles of cisplatin plus pemetrexed and exhibited a partial response. Because his serum creatinine increased, pemetrexed maintenance therapy (PMT) was adopted, and 18 cycles were successfully delivered and the patient achieved a complete response. This case suggests that PMT could thus be useful for treating MPM.

In plain English

This case report, by doctors in Japan, described a 69-year-old man with epithelial-type malignant pleural mesothelioma, stage III (T3, N0, M0). He had a two-year history of asbestos exposure starting at age 20. No fiber type or job was named. He received cisplatin plus pemetrexed every 21 days for five cycles and had a good partial response. He and his family declined surgery with radiation. After his serum creatinine rose to 1.56 mg/dL following the fifth cycle, he was switched to pemetrexed alone as maintenance therapy every 28 days. A complete response was seen on day 25 of the sixth maintenance cycle. He received 18 maintenance courses without progression for 22 months from the start of chemotherapy. The response ended when multiple liver metastases were found during the 19th cycle. The authors described the toxicity of maintenance therapy in this patient with kidney dysfunction as negligible and tolerable. They concluded that this approach could be promising but remains experimental and needs testing in phase III trials. They said any explanation was only theoretical, as molecular marker data were lacking.

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 report (single patient)
• Who was studied: One 69-year-old man with right chest pain, diagnosed with epithelial-type malignant pleural mesothelioma, International Mesothelioma Interest Group stage III (T3, N0, M0); the authors are at Uji Tokushukai Medical Center, Japan
• Exposure: Two years of asbestos exposure beginning at age 20 (no fiber type, product or job stated). The treatment reported was cisplatin plus pemetrexed, followed by pemetrexed maintenance therapy.
• Main results:
  • Biopsy and calretinin staining confirmed epithelial-type malignant pleural mesothelioma, stage III
  • Cisplatin plus pemetrexed every 21 days for five cycles produced a good partial response by day 17 of the third cycle
  • Serum creatinine rose to 1.56 mg/dL after the fifth cycle, so pemetrexed maintenance therapy was started. It was given every 28 days because of grade four neutropenia in the fifth cycle of induction therapy.
  • A complete response was seen on day 25 of the sixth maintenance cycle
  • The patient received 18 courses of maintenance therapy without progression for 22 months from the start of induction chemotherapy
  • The complete response ended when multiple liver metastases were detected on day 25 of the 19th maintenance cycle
  • The authors described the toxicity of maintenance therapy in this patient with renal dysfunction as negligible and tolerable. This statement did not cover the induction phase, during which creatinine rose and grade four neutropenia occurred.
• The authors' conclusion: The authors concluded that giving a higher total dose of pemetrexed through maintenance therapy to avoid cisplatin toxicity could be promising. They added that the approach still remains experimental and should be validated by phase III trials.
• Limitations the authors state:
  • The authors stated that the mechanism behind the result is only theoretical, because data on molecular markers (such as TS and ERCC1) were lacking

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: Progression-Free Survival, Pemetrexed (Alimta), Cisplatin, Chemotherapy, Pleural Mesothelioma, Prognosis.

Related studies

• Survival after trimodality therapy for malignant pleural mesothelioma: Radical Pleurectomy, chemotherapy with Cisplatin/Pemetrexed and radiotherapy — S. Bölükbas, C. Manegold, et al. (2011)
• Gemcitabine and vinorelbine as second-line or beyond treatment in patients with malignant pleural mesothelioma pretreated with platinum plus pemetrexed chemotherapy — G. Toyokawa, M. Takenoyama, et al. (2014)
• Chemotherapy maintenance: an option for prolonged survival in malignant peritoneal mesothelioma? — S. Hofer, B. Sasse, et al. (2010)
• Successful salvage chemotherapy with gemcitabine and vinorelbine in a malignant pleural mesothelioma patient previously treated with pemetrexed — T. Agatsuma, T. Koizumi, et al. (2010)
• Pharmacogenetics of pemetrexed combination therapy in lung cancer: pathway analysis reveals novel toxicity associations — A. Corrigan, J.L. Walker, et al. (2014)
• Combination effect of photodynamic therapy using NPe6 with pemetrexed for human malignant pleural mesothelioma cells — S. Maehara, J. Usuda, et al. (2015)

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