The role of pemetrexed in recurrent epithelial ovarian cancer: A scoping review
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.
Siegel R. Cancer Statistics. CA: A Cancer Journal for Clinicians 2017; 67: 7-30.
Rosenthal A, Menon U, Jacobs I. Screening for ovarian cancer. Clinical Obstetrics and Gynecology 2006; 49: 433-47.
Jelovac D, Armstrong DK. Recent progress in the diagnosis and treatment of ovarian cancer. CA: A Cancer Journal for Clinicians 2011; 61:183-203
Tomao F, Panici P, Frati L, Tomao S. Emerging role of pemetrexed in ovarian cancer. Expert Review of Anticancer Therapy 2009; 9: 1727-35.
Piccart M, Green J, Lacave A, et al. Oxaliplatin or paclitaxel in patients with platinum-pretreated advanced ovarian cancer: a randomized phase II study of the European Organization for Research and Treatment of Cancer Gynecology Group. Journal of Clinical Oncology 2000; 18:1193-202.
Gordon A, Tonda M, Sun S, et al. Long-term survival advantage for women treated with pegylated liposomal doxorubicin compared with topotecan in a phase 3 randomized study of recurrent and refractory epithelial ovarian cancer. Gynecologic Oncology 2004; 95: 1-8.
Meier W, du Bois A, Reuss A, et al. Topotecan versus treosulfan, an alkylating agent, in patients with epithelial ovarian cancer and relapse within 12 months following 1st-line platinum/paclitaxel chemotherapy. A prospectively randomized Phase III trial by the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study Group (AGO-OVAR). Gynecologic Oncology 2009; 114: 199-205.
Mutch D, Orlando M, Goss T, et al. Randomized Phase III trial of gemcitabine compared with PEGylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer. Journal of Clinical Oncology 2007; 25(19): 2811-8.
Ferrandina G, Ludovisi M, Lorusso D, et al. Phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in progressive or recurrent ovarian cancer. Journal of Clinical Oncology 2008; 26(6): 890-6.
fda.gov. Drug Facts Alimta 2012; Available from: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021462s039lbl.pdf.
Corona G, Giannini F, Fabris M, et al. Role of folate receptor and reduced folate carrier in the transport of 5-methyltetrahydrofolic acid in human ovarian carcinoma cells. Int J Cancer 1988; 75: 125-33.
Miotti S, Bagnoli M, Ottone F, et al. Simultaneous activity of two different mechanisms of folate transport in ovarian carcinoma cell lines. J Cell Biochem 1997; 65: 479-91.
NCCN Guidelines for Patients: Ovarian Cancer 2017; Available from: www.nccn.org/professionals/physician_gls/PDF/ovarian.pdf.
Arksey H, O'Malley L. Scoping studies: towards a methodological framework. International Journal of Social Research Methodology 2005; 8: 19-32.
Rustsoven J, Eisenhauer E, Butts C, et al. Multitargeted antifolate, LY231514, as first-line chemotherapy for patients with advanced non-small-cell lung cancer: a phase II study â€“ National Cancer Institute of Canada Clinical Trials Group. J. Clin. Oncol 1999; 17: 1194-9.
Rinaldi D. Overview of phase I trials of multitargeted antifolate (MTA, LY231514). Semin Oncol 1999; 23: 82-8.
Niyikiza C, Baker S, Seitz D, et al. Homocysteine and methylmalonic acid: markers to predict and avoid toxicity from pemetrexed therapy. Mol Cancer Ther 2002; 1: 545-52.
Scagliotti G, Shin D, Kindler H, et al. Phase II study of pemetrexed with and without folic acid and vitamin B12 as front-line therapy in malignant pleural mesothelioma. J Clin Oncol 2003; 21: 1556-61.
Vogelzang N, Rusthoven J, Symanowski J, et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol 2003; 21: 2636-44.
Misset J, Gamelin E, Campone M, et al. Phase I and pharmacokinetic study of the multitargeted antifolate pemetrexed in combination with oxaliplatin in patients with advanced solid tumors. Annals of Oncology 2004; 15: 1123-9.
Hensley M, Larkin J, Fury M, et al. A phase I trial of pemetrexed plus gemcitabine given biweekly with B-vitamin support in solid tumor malignancies or advanced epithelial ovarian cancer. Clin Cancer Res 2008; 14: 6310-6.
Sehouli J, Camara O, Mahner S, et al. A phase I trial of pemetrexed plus carboplatin in recurrent ovarian cancer. Cancer Chemother Pharmacol 2010; 68: 861-8.
Richards D, Loesch D, Vukelja S, et al. A phase I study of pemetrexed and PEGylated liposomal doxorubicin in patients with refractory breast, ovarian, primary peritoneal, or fallopian tube cancer. Invest New Drugs 2011; 29: 963-70.
Chambers S, Chow H, Janicek M, et al. Phase I trial of intraperitoneal pemetrexed, cisplatin, and paclitaxel in optimally debulked ovarian cancer. Clin Cancer Res 2012; 18: 2668-78.
Miller D, Blessing J, Krasner C, et al. Phase II evaluation of pemetrexed in the treatment of recurrent or persistent platinum-resistant ovarian or primary peritoneal carcinoma: a study of the Gynecologic Oncology Group. J Clin Oncol 2009; 27: 2686-91.
Vergote I, Calvert H, Kania M, et al. A randomised, double-blind, phase II study of two doses of pemetrexed in the treatment of platinum-resistant, epithelial ovarian or primary peritoneal cancer. Eur J Cancer 2009; 45: 1415-23.
Sehouli J, Alvarez A, Manouchehrpour S, et al. A phase II trial of pemetrexed in combination with carboplatin in patients with recurrent ovarian or primary peritoneal cancer. Gynecol Oncol 2011; 124: 205-9.
Matulonis U, Horowitz N, Campos S, et al. Phase II study of carboplatin and pemetrexed for the treatment of platinum-sensitive recurrent ovarian cancer. J Clin Oncol 2008; 26: 5761-6.
Garin A, Manikhas A, Biakhov M, et al. Phase II study of pemetrexed and carboplatin in patients with locally advanced or metastatic breast cancer. Breast Cancer Res Treat 2008; 110: 309-15.
Socinski M, Weissman C, Hart L, et al. Randomized phase II trial of pemetrexed combined with either cisplatin or carboplatin in untreated extensive-stage small-cell lung cancer. J Clin Oncol 2006; 24: 4840-7.
Hagemann A, Novetsky A, Zighelboim I, et al. Phase II study of bevacizumab and pemetrexed for recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal cancer. Gynecologic Oncology 2013; 131: 535-40.
Ledermann J, Stebbing J. Positioning pemetrexed in the treatment of ovarian cancer. Eur J Cancer 2009; 45: 1330-2.
Morotti M, Valenzano Menada M, et al. Pemetrexed disodium in ovarian cancer treatment. Expert Opin Investig Drugs 2012; 21: 437-49.
Miller D, Tai D, Obasaju C, Vergote I. Safety and efficacy of pemetrexed in gynecologic cancers: A systematic literature review. Modern Chemotherapy 2013; 2: 19-32.
Egloff H, Jatoi A. Pemetrexed for ovarian cancer: a systematic review of the published literature and a consecutive series of patients treated in a nonclinical setting. Case Reports in Oncology 2014; 7: 541-9.
Smith I. Phase II studies of pemetrexed in metastatic breast and gynecologic cancers. Oncology (Williston Park) 2004; 18: 63-5.
Gomez H, Santillana S, Vallejos C, et al. A phase II trial of pemetrexed in advanced breast cancer: clinical response and association with molecular target expression. Clinical Cancer Research 2006; 12: 832-8.
Chamizo C, Zazo S, DÃ³mine M, et al. Thymidylate synthase expression as a predictive biomarker of pemetrexed sensitivity in advanced non-small cell lung cancer. BMC Pulmonary Medicine 2015; 15: 132.
Nicolson M, Fennell D, Ferry D, et al. Thymidylate synthase expression and outcome of patients receiving pemetrexed for advanced nonsquamous non-small-cell lung cancer in a prospective blinded assessment phase II clinical trial 2013; J Thorac Oncol. 8: 930-9.
Righi L, Papotti M, Ceppi P, et al. Thymidylate synthase but not excision repair cross-complementation group 1 tumor expression predicts outcome in patients with malignant pleural mesothelioma treated with pemetrexed-based chemotherapy 2010; J Clin Oncol. 28: 1534â€“9.
Sun J, Ahn J, Jung S, et al. Pemetrexed plus cisplatin versus gemcitabine plus cisplatin according to thymidylate synthase expression in nonsquamous non-small-cell lung cancer: a biomarker-stratified randomized phase II trial. J Clin Oncol 2015; 33: 2450-6.
Sun J, Han J, Ahn J, et al. Significance of thymidylate synthase and thyroid transcription factor 1 expression in patients with nonsquamous non-small cell lung cancer treated with pemetrexed-based chemotherapy. J Thorac Oncol 2011; 6: 1392â€“9.
Takezawa K, Okamoto I, Okamoto W, et al. Thymidylate synthase as a determinant of pemetrexed sensitivity in non-small cell lung cancer. British Journal of Cancer 2011; 104: 1594-601.
Mou W, Xue H, Tong H. Prognostic value of serum leptin in advanced lung adenocarcinoma patients with cisplatin/pemetrexed chemotherapy. Oncol Lett 2014; 7: 2073-8.
Shi S, Wang M, Tian J. MicroRNA 25, microRNA 145, and microRNA 210 as biomarkers for predicting the efficacy of maintenance treatment with pemetrexed in lung adenocarcinoma patients who are negative for epidermal growth factor receptor mutations or anaplastic lymphoma kinase translocations. Transl Res 2016; 170: 1-7.
ClinicalTrials.Gov. Pemetrexed disodium and carboplatin in treating patients with recurrent ovarian, primary peritoneal or fallopian tube cancer. [Online]. Available from: https://clinicaltrials.gov/ct2/show/NCT01001910.
ClinicalTrials.Gov. Methoxyamine, cisplatin, and pemetrexed disodium in treating patients with advanced solid tumors or mesothelioma that cannot be removed by surgery or mesothelioma that is refractory to pemetrexed disodium and cisplatin or carboplatin. [Online]. Available from: https://clinicaltrials.gov/show/NCT02535312.
ClinicalTrials.Gov. Bosutinib in combination with pemetrexed in patients with selected metastatic solid tumors. [Online]. Available from: https://clinicaltrials.gov/show/NCT03023319.
Schultz R.M. Preclinical development of AlimtaTM (Pemetrexed, LY231514), a multitargeted antifolate. In: Herrling P.L., Matter A., Schultz R.M. (eds) Advances in Targeted Cancer Therapy. Progress in Drug Research, 2015; 63. Birkhauser Basel.
Rollins K, Lindley C. Pemetrexed: a multitargeted antifolate. Clin Ther 2005; 27: 1342-82.
Goldman I, Zhao R. Molecular, biochemical, and cellular pharmacology of pemetrexed. Semin Oncol 2002; 29: 3-17.
Adjei A. Pemetrexed (ALIMTA), A Novel Multitargeted Antineoplastic Agent. Clin Cancer Res 2004; 10: 4276s-80s.
Kano Y, Akutsu M, Tsunoda S, et al. Schedule-Dependent Interactions Between Pemetrexed and Cisplatin in Human Carcinoma Cell Lines In Vitro. Oncol Res 2006; 16: 85-95.
Bookman M, Brady M, McGuire W, et al.b Evaluation of New Platinum-Based Treatment Regimens in Advanced-Stage Ovarian Cancer: A Phase III Trial of the Gynecologic Cancer InterGroup. J Clin Oncol 2009; 27: 1419-25.
PlumX Metrics provide insights into the ways people interact with individual pieces of research output (articles, conference proceedings, book chapters, and many more) in the online environment. Examples include, when research is mentioned in the news or is tweeted about. Collectively known as PlumX Metrics, these metrics are divided into five categories to help make sense of the huge amounts of data involved and to enable analysis by comparing like with like.
Copyright (c) 2018 Michael Roche, Laura Parisi, Linda Li, Amy Knehans, Rebecca Phaeton, Joshua P. Kesterson
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.