The current state of pemetrexed in ovarian cancer

Our plain-English summary of The current state of pemetrexed in ovarian cancer, by R.E. Miller, S. Banerjee (Expert Opinion on Investigational Drugs, 2013).

The study

• Authors: R.E. Miller, S. Banerjee
• Journal: Expert Opinion on Investigational Drugs
• Published: 2013;22(9):1201-10
• Type of article: Review
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: Pemetrexed is a multitargeted antifolate drug that has shown benefit in several clinical trials in solid tumors. It is currently approved for the treatment of nonsmall cell lung cancer (NSCLC) and mesothelioma, and is being explored in epithelial ovarian cancer.

Areas Covered: In this article, the clinical development of pemetrexed in relation to ovarian cancer is discussed. Early phase clinical trials using pemetrexed monotherapy or in combination with other cytotoxic or target agents are reviewed. The safety profile of pemetrexed will also be evaluated.

Expert Opinion: A number of Phase I and II clinical trials have evaluated the use of pemetrexed in patients with ovarian cancer. Thus far, there are no randomized studies that address the role of pemetrexed compared to current, standard treatments. The activity of single agent pemetrexed in platinum-resistant patients is worth exploring. Biomarker-driven randomized, clinical trials and patient selection are key for the future development of pemetrexed.

In plain English

This article was a review of other researchers' trials, not an original study, and it was not about asbestos. The authors reviewed early-phase (Phase I and II) clinical trials of pemetrexed, a cancer drug, in women with epithelial ovarian cancer. They searched PubMed for English-language articles up to February 2013. They noted that pemetrexed was approved in Europe for malignant pleural mesothelioma, together with cisplatin, but that no drug of its type was approved for ovarian cancer. In a Gynecologic Oncology Group trial they reviewed, pemetrexed alone in platinum-resistant disease gave a 21% overall response rate and a median progression-free survival of 2.9 months. A second trial compared two doses and reported response rates of 9.3% and 10.4%. Adding pemetrexed to other chemotherapy drugs was associated with high rates of severe side effects. The authors concluded that there were no randomized trials against standard treatment, so pemetrexed could not be recommended for routine use. They said its role in platinum-resistant disease was worth exploring further.

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: Narrative review (drug evaluation) of published clinical trials and conference abstracts; no new patients were studied
• Who was studied: Published English-language studies found in PubMed up to February 2013, plus American Society of Clinical Oncology and American Association for Cancer Research abstracts from 2009 to 2012, on pemetrexed in patients with epithelial ovarian cancer
• Exposure: No asbestos exposure was studied. The subject was the drug pemetrexed, a multitargeted antifolate, given alone or with other drugs (carboplatin, gemcitabine, pegylated liposomal doxorubicin, bevacizumab and others). Mesothelioma appears only as an approved use of the drug: malignant pleural mesothelioma, in combination with cisplatin.
• Main results:
  • As reported for the reviewed Gynecologic Oncology Group trial: 51 patients with platinum-resistant ovarian cancer received single-agent pemetrexed at 900 mg/m2. The overall response rate was 21% (1 complete response, 2%; 9 partial responses, 19%) and the median progression-free survival was 2.9 months.
  • As reported for the reviewed randomized Phase II trial by Vergote and colleagues: 102 platinum-resistant patients received pemetrexed at 500 or 900 mg/m2. The overall response rate was 9.3% in the 500 mg/m2 group and 10.4% in the 900 mg/m2 group, with a median progression-free survival of 2.8 months in both groups.
  • As reported for the reviewed Phase II trial by Matulonis and colleagues: patients with platinum-sensitive recurrent disease received carboplatin plus pemetrexed. There were no complete responses; 51.1% had a partial response, and the median progression-free survival was 7.6 months.
  • The authors summarized that adding pemetrexed to platinum, gemcitabine or pegylated liposomal doxorubicin was associated with a high incidence of grade 3 and 4 toxicity, such as neutropenia in 39 to 86% of patients, which must be weighed against promising early response rates.
• The authors' conclusion: The authors concluded that, because there are no randomized studies of pemetrexed against standard care, pemetrexed cannot be recommended for routine clinical use in ovarian cancer. They added that its role in platinum-resistant disease is worth exploring further, with biomarker-based randomized trials.
• Limitations the authors state:
  • The authors stated that the Phase I studies were small, so it is difficult to draw conclusions from them.
  • The authors stated that no randomized studies have compared pemetrexed with standard care.

Topics

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

Medical terms in this study, explained in our Lexicon: Pemetrexed (Alimta), Ovarian Cancer, Antifolate, Clinical Trial, Lung Cancer, Mesothelioma, Biomarker.

Related studies

• Molecular resistance fingerprint of pemetrexed and platinum in a long-term survivor of mesothelioma — O.D. Røe, A. Szulkin, et al. (2012)
• Interaction and cross-resistance of cisplatin and pemetrexed in malignant pleural mesothelioma cell lines — M. Kitazono-Saitoh, Y. Takiguchi, et al. (2012)
• Retreatment with pemetrexed-based chemotherapy in patients with malignant pleural mesothelioma — G.L. Ceresoli, P.A. Zucali, et al. (2011)
• Enhanced apoptosis by pemetrexed and simvastatin in malignant mesothelioma and lung cancer cells by reactive oxygen species-dependent mitochondrial dysfunction and Bim induction — K.E. Hwang, Y.S. Kim, et al. (2014)
• Death receptor 5 and cellular FLICE-inhibitory protein regulate pemetrexed-induced apoptosis in human lung cancer cells — L. Su, G. Liu, et al. (2011)
• Pharmacokinetic evaluation of pemetrexed — J.B. Sørensen (2011)

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