Pemetrexed Safety and Pharmacokinetics in Patients with Third-Space Fluid

Dickgreber, N; Sørensen, Jens Benn; Paz‐Ares, Luis; Schytte, Tine; Latz, Jane E.; Schneck, Karen B.; Yuan, Zheng; Sánchez-Torres, J.M.

doi:10.1158/1078-0432.ccr-09-3324

Cited by 17 publications

(9 citation statements)

References 34 publications

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“…Pemetrexed is transported into cells mainly by the reduced folate carrier and undergoes rapid intracellular transformation by folyl-polyglutamatesynthase to the more potent polyglutamate derivative [5]. Other than with methotrexate, third-space accumulation does not seem to play a clinically significant role with pemetrexed [6]. As pemetrexed is often combined with potentially nephrotoxic cisplatin, adequate monitoring of renal function is important.…”

Section: Discussionmentioning

confidence: 99%

Interstitial Pneumonitis after Treatment with Pemetrexed: A Rare Event?

Hochstrasser

Benz²,

Joerger³

et al. 2012

Chemotherapy

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Background: Pneumonitis after pemetrexed has been rarely reported in conjunction with radiation therapy. Methods: Two cases of pemetrexed-induced pneumonitis in different clinical settings and with unequal outcomes are discussed with a review of the literature. Results: Two patients with stage IIIB non-small cell lung cancer developed interstitial lung disease after chemotherapy with pemetrexed. The first patient was previously treated with thoracic radiotherapy, and radiation pneumonitis was initially suspected. He died shortly after pemetrexed reexposition. The second patient developed pemetrexed-induced interstitial lung disease despite no prior radiotherapy. After discontinuation of pemetrexed and administration of steroids, pneumonitis resolved completely. Conclusion: Interstitial lung disease is a rare but potentially fatal side effect of pemetrexed. It occurs more often after radiotherapy but can also be encountered in the absence of radiotherapy. Reexposition to pemetrexed may lead to severe interstitial lung disease and even death and should be strictly avoided.

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Section: Discussionmentioning

confidence: 99%

Interstitial Pneumonitis after Treatment with Pemetrexed: A Rare Event?

Hochstrasser

Benz²,

Joerger³

et al. 2012

Chemotherapy

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“…The drug has a small steady-state volume of distribution of approximately 15 litres and is rapidly eliminated from plasma through urinary excretion with a half-life of 2 to 5 h at doses of 525-700 mg/m 2 . Third-space accumulation does not appear to play a clinically prominent role (14). Since pemetrexed is frequently combined with potentially nephrotoxic cisplatin, monitoring of renal function is mandatory.…”

Section: Pemetrexedmentioning

confidence: 99%

“…Pemetrexed administration is commonly followed by certain adverse reactions (14,23). These manifestations include myelosuppression (anemia, neutropenia and thrombopenia), and various digestive tract dysfunctions such as nausea, vomiting, diarrhea, constipation, anorexia, stomatitis or oral erosions (24).…”

Section: Cutaneous Adverse Reactionsmentioning

confidence: 99%

Revisiting cutaneous adverse reactions to pemetrexed

et al. 2011

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Abstract. Pemetrexed (Alimta ® ) is a multitargeted antifolate drug approved as a single agent or in combination with cisplatin for the treatment of a small number of malignancies including advanced and metastatic non-squamous non-small cell lung cancer (NSCLC), and malignant pleural mesothelioma. This review reports the recent peer-reviewed publications and original findings regarding cutaneous adverse reactions (CARs) to pemetrexed. Pemetrexed-related CARs are frequently reported under the unspecific term 'skin rash'. However, more specific diseases were tentatively identified as alopecias, urticarial vasculitis, acute generalized exanthematous pustulosis, toxic epidermal necrolysis, radiation recall dermatitis and pityriasis lichenoides. Most of the skin reactions occur shortly after pemetrexed administration. As with methotrexate-related CARs, the cell cycle arrest in the S phase may be regarded as a direct and major cause of the cytotoxic pathobiology. An adverse immune reaction is unlikely. In conclusion, pemetrexed is responsible for CARs exhibiting a variety of clinical presentations. Their origin is likely attributed to direct cytotoxicity following the cell cycle arrest in the S phase and cell necrosis.

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“…Interestingly, pemetrexed is also indicated, in combination with cisplatin, for first‐line therapy and, as single‐agent, for second‐line treatment of patients with advanced non‐squamous NSCLC, a patient group where MPE is extremely frequent. As the drug appears to be safe in patients with MPE, antifolates could present a promising therapeutic agent for adenocarcinoma‐induced MPE in the future 87 . Translational research into antifolates against MPM and MPE is ever expanding, including studies on intrapleural administration, prediction of response to therapy and molecular mechanisms of function 88 …”

Section: Reviewmentioning

confidence: 99%

“…2,84,85 Recent work expanded the role of pemetrexed suggesting that is also effective as maintenance therapy and in the retreatment of recurrent MPM and that its efficacy and safety is not compromised by the presence of a pleural effusion. 86,87 Interestingly, pemetrexed is also indicated, in combination with cisplatin, for first-line therapy and, as single-agent, for second-line treatment of patients with advanced non-squamous NSCLC, a patient group where MPE is extremely frequent. As the drug appears to be safe in patients with MPE, antifolates could present a promising therapeutic agent for adenocarcinoma-induced MPE in the future.…”

Section: Systemic Therapy Of Malignant Pleural Diseasesmentioning

confidence: 99%

Translational advances in pleural malignancies

Stathopoulos

2010

Respirology

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Pleural malignancies, including primary malignant pleural mesothelioma and secondary pleural metastasis of various tumours resulting in malignant pleural effusion, are frequent and lethal diseases that deserve devoted translational research efforts for improvements to be introduced to the clinic. This paper highlights select clinical advances that have been accomplished recently and that are based on preclinical research on pleural malignancies. Examples are the establishment of folate antimetabolites in mesothelioma treatment, the use of PET in mesothelioma management and the discovery of mesothelin as a marker of mesothelioma. In addition to established translational advances, this text focuses on recent research findings that are anticipated to impact clinical pleural oncology in the near future. Such progress has been substantial, including the development of a genetic mouse model of mesothelioma and of transplantable models of pleural malignancies in immunocompetent hosts, the deployment of stereological and imaging methods for integral assessment of pleural tumour burden, as well as the discovery of the therapeutic potential of aminobiphosphonates, histone deacetylase inhibitors and ribonucleases against malignant pleural disease. Finally, key obstacles to overcome towards a more rapid advancement of translational research in pleural malignancies are outlined. These include the dissection of cell-autonomous and paracrine pathways of pleural tumour progression, the study of mesothelioma and malignant pleural effusion separately from other tumours at both the clinical and preclinical levels, and the expansion of tissue banks and consortia of clinical research of pleural malignancies.

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Pemetrexed Safety and Pharmacokinetics in Patients with Third-Space Fluid

Cited by 17 publications

References 34 publications

Interstitial Pneumonitis after Treatment with Pemetrexed: A Rare Event?

Interstitial Pneumonitis after Treatment with Pemetrexed: A Rare Event?

Revisiting cutaneous adverse reactions to pemetrexed

Translational advances in pleural malignancies

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