The role of pemetrexed in recurrent epithelial ovarian cancer: A scoping review

Our plain-English summary of The role of pemetrexed in recurrent epithelial ovarian cancer: A scoping review, by M. Roche, L. Parisi, L. Li, et al (Oncology Reviews, 2018).

The study

• Authors: M. Roche, L. Parisi, L. Li, A. Knehans, R. Phaeton, J.P. Kesterson
• Journal: Oncology Reviews
• Published: 2018;12(1):346
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Ovarian cancer is the leading cause of mortality among gynecologic malignancies, with most cases diagnosed at an advanced stage. Despite an initial response, most develop a recurrence and subsequent resistance to standard therapies. Pemetrexed (AlimtaTM) is a new generation multi-targeted antifolate initially approved for the treatment of malignant pleural mesothelioma. In recent years, it has shown promise in the treatment of recurrent epithelial ovarian cancer. In this review, we outline the current literature and discuss the future of pemetrexed in the setting of recurrent epithelial ovarian cancer.

In plain English

This article was a scoping review of published research on pemetrexed, a chemotherapy drug first approved for malignant pleural mesothelioma, as a treatment for recurrent epithelial ovarian cancer. It was not an original study and did not study asbestos exposure. The authors searched MEDLINE, the Cochrane Library, trial registries and Google Scholar up to November 24, 2017, and included only English-language studies in humans. Of 26 results, 16 met their criteria: five phase I trials, five phase II trials, five systematic reviews and one expert commentary. In the reviewed phase II trials of pemetrexed alone in platinum-resistant disease, one trial reported a 21% response rate. Another reported 9.3% at 500 mg/m2 and 10.4% at 900 mg/m2, with more serious side effects at the higher dose. Two trials of pemetrexed with carboplatin in platinum-sensitive disease reported response rates of 51.1% and 32.8%. The authors concluded that pemetrexed had shown responses that warranted continued investigation. They noted that no published study had directly compared it with other treatments.

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: Scoping review of the published literature and trial registries, using the five-step method of Arksey and O'Malley
• Who was studied: 16 publications selected from 26 search results (MEDLINE, Cochrane Library, ClinicalTrials.gov and other registries, Google Scholar), current to November 24, 2017: five phase I trials, five phase II trials, five systematic reviews and one expert commentary on pemetrexed in recurrent ovarian cancer
• Exposure: Treatment with pemetrexed, a multi-targeted antifolate chemotherapy drug, alone or combined with oxaliplatin, gemcitabine, carboplatin, pegylated liposomal doxorubicin, intraperitoneal cisplatin and paclitaxel, or bevacizumab. No asbestos exposure was studied.
• Main results:
  • In the reviewed trial by Miller and colleagues, single-agent intravenous pemetrexed 900 mg/m2 every 21 days was given to patients with platinum-resistant recurrent ovarian cancer (48 patients in the text, 51 in Table 2). The overall response rate was 21%, with one complete response.
  • In the reviewed trial by Vergote et al., patients with platinum-resistant recurrent ovarian cancer received low dose (500 mg/m2, 47 patients) or high dose (900 mg/m2, 51 patients) pemetrexed. Response rates were 9.3% and 10.4%, and median progression-free survival was 11.9 and 10.3 months. The high dose had more serious drug-related adverse events, including two deaths possibly related to treatment.
  • In the reviewed trial by Matulonis et al., pemetrexed 500 mg/m2 with carboplatin was given to patients with platinum-sensitive recurrent ovarian cancer. The response rate was 51.1%, with no complete responses, and median progression-free survival was 7.57 months.
  • In the reviewed trial by Sehouli and colleagues, carboplatin AUC 6 plus pemetrexed 500 mg/m2 was given in platinum-sensitive recurrent ovarian cancer. Of 61 evaluable patients, 20 (32.8%) responded, one completely. Median progression-free survival was 9.4 months, and one patient died of multiple organ failure possibly related to chemotherapy.
  • In the reviewed trial by Hagemann, pemetrexed 500 mg/m2 plus bevacizumab 15 mg/kg was given to 34 patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer. The response rate was 41%, with zero complete responses. Median progression-free survival was 7.9 months and median overall survival 25.7 months. Two patients developed hematologic malignancies.
  • The authors reported that pemetrexed had been most extensively studied at 500 mg/m2 every 21 days with vitamin supplementation.
• The authors' conclusion: The authors concluded that pemetrexed had shown responses in a typically chemoresistant population that warrant continued investigation, and that further studies comparing it to current therapies for recurrent ovarian cancer are warranted.
• Limitations the authors state:
  • The search included only English-language publications and studies in humans.
  • The authors stated that no published studies had directly compared pemetrexed with other treatments, and no such studies were listed as recruiting.
  • The authors stated that, despite promising early trials, the efficacy of pemetrexed in recurrent ovarian cancer requires further study.

Topics

Medical terms in this study, explained in our Lexicon: Pemetrexed (Alimta), Ovarian Cancer, Antifolate, Pleural Mesothelioma.

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