Pemetrexed: A multitargeted antifolate

Rollins, Kristan; Lindley, Celeste

doi:10.1016/j.clinthera.2005.09.010

Cited by 118 publications

(84 citation statements)

References 109 publications

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“…PMX is a multitargeted antifolate, which is clinically approved for the treatment of pleural mesothelioma and non-small cell lung cancer in combination with cisplatin (17)(18)(19). Moreover, PMX is currently being tested in a number of clinical trials for the treatment of several other cancer types (reviewed in ref.…”

Section: Introductionmentioning

confidence: 99%

177Lu-EC0800 Combined with the Antifolate Pemetrexed: Preclinical Pilot Study of Folate Receptor Targeted Radionuclide Tumor Therapy

Reber

Haller

Leamon

et al. 2013

Molecular Cancer Therapeutics

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Targeted radionuclide therapy has shown impressive results for the palliative treatment of several types of cancer diseases. The folate receptor has been identified as specifically associated with a variety of frequent tumor types. Therefore, it is an attractive target for the development of new radionuclide therapies using folatebased radioconjugates. Previously, we found that pemetrexed (PMX) has a favorable effect in reducing undesired renal uptake of radiofolates. Moreover, PMX also acts as a chemotherapeutic and radiosensitizing agent on tumors. Thus, the aim of our study was to investigate the combined application of PMX and the therapeutic radiofolate 177 Lu-EC0800. Determination of the combination index (CI) revealed a synergistic inhibitory effect of 177 Lu-EC0800 and PMX on the viability of folate receptor-positive cervical (KB) and ovarian (IGROV-1) cancer cells in vitro (CI < 0.8). In an in vivo study, tumor-bearing mice were treated with 177 Lu-EC0800 (20 MBq) and a subtherapeutic (0.4 mg) or therapeutic amount (1.6 mg) of PMX. Application of 177 Lu-EC0800 with PMX ther resulted in a two-to four-fold enhanced tumor growth delay and a prolonged survival of KB and IGROV-1 tumor-bearing mice, as compared to the combination with PMX subther or untreated control mice. PMX subther protected the kidneys from undesired side effects of 177 Lu-EC0800 (20 MBq) by reducing the absorbed radiation dose. Intact kidney function was shown by determination of plasma parameters and quantitative single-photon emission computed tomography using 99m Tc-DMSA. Our results confirmed the anticipated dual role of PMX. Its unique features resulted in an improved antitumor effect of folate-based radionuclide therapy and prevented undesired radio-nephrotoxicity. Mol Cancer Ther; 12(11); 2436-45. Ó2013 AACR.

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Section: Introductionmentioning

confidence: 99%

177Lu-EC0800 Combined with the Antifolate Pemetrexed: Preclinical Pilot Study of Folate Receptor Targeted Radionuclide Tumor Therapy

Reber

Haller

Leamon

et al. 2013

Molecular Cancer Therapeutics

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“…The initial development of so-called new multi-target antifolates has been hampered by severe side-effects. These effects have been reduced by the paradox of supplementing folates [9,10] which permits the use of other TS inhibitors, like Pemetrexed, with an acceptable risk for the patient without know reduction of treatment effect [11,12]. The role of Pemetrexed (Alimta) in the neoadjuvant treatment of rectal cancer is unknown.…”

Section: Introductionmentioning

confidence: 99%

A phase I/II study of neoadjuvant chemotherapy with Pemetrexed (Alimta) in rectal cancer

Derwinger

Kodeda

Swartling

et al. 2011

European Journal of Surgical Oncology (EJSO)

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AimThe aim was to assess the feasibility of preoperative chemotherapy and possible tumour response using Pemetrexed (Alimta) in rectal cancer. MethodThe study was a prospective, non-randomized, single centre phase I/II feasibility trial. 37 patients with resectable rectal cancer were recruited and given three 3 week cycles of preoperative Pemetrexed therapy. Tumour size and stage were assessed by MRI scans before and after chemotherapy. Treatment tolerability and response such as changes in tumour size and symptoms were assessed. ResultsAll patients completed the chemotherapy. Whilst mild side effects were frequent (grade 1, 34/37), the risk of severe effects was limited (grade 3 or 4, 4/37). Overall, there was a significant reduction in tumour size (p<0.001). By RECIST criteria, one patient had tumour progression, 23/36 had stable disease and 12 patients had a response of up to 65%. There was also a significant decrease in the number of pretreatment symptoms (p<0.018) including reduction of bleeding and diarrhoea/constipation. ConclusionPreoperative (Neoadjuvant) treatment with Pemetrexed was feasible in studied patients. Serious side effects were limited and a radiological tumour response or stable disease was seen in a majority of patients.

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“…In a multivariate regression analysis of prognostic factors derived from EMPHACIS trial, predictive variables that seem to be related to longer OS were represented by therapy group, vitamin supplementation, Karnofsky performance status, stage of disease, histologic subtype and white blood cell count (40). A retrospective study of 60 patients with MPM receiving pemetrexed correlated low thymidylate synthase levels with improved outcome (41).…”

Section: First-line Combination Ctmentioning

confidence: 99%

Chemotherapy treatment in malignant pleural mesothelioma: a difficult history

et al. 2018

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Malignant pleural mesothelioma (MPM) is a rare neoplasm that typically arises from mesothelial surfaces of the pleural cavity. Despite treatment improvements, it carries a dismal prognosis. The majority of patients either have unresectable disease or are not candidates for surgery due to medical comorbidities or old age. For such patients, chemotherapy (CT) represents the gold-standard treatment. To date, combination CT with cisplatin plus pemetrexed represents the most widely used regimen in first-line setting for patients with unresectable MPM. Other first-line options are currently available, including the use of raltitrexed instead of pemetrexed combined with platinum. In this review, we discuss the role of CT in MPM mainly focusing on the results of the trials conducted in first-line setting.

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Pemetrexed: A multitargeted antifolate

Cited by 118 publications

References 109 publications

177Lu-EC0800 Combined with the Antifolate Pemetrexed: Preclinical Pilot Study of Folate Receptor Targeted Radionuclide Tumor Therapy

177Lu-EC0800 Combined with the Antifolate Pemetrexed: Preclinical Pilot Study of Folate Receptor Targeted Radionuclide Tumor Therapy

A phase I/II study of neoadjuvant chemotherapy with Pemetrexed (Alimta) in rectal cancer

Chemotherapy treatment in malignant pleural mesothelioma: a difficult history

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