Acute generalized exanthematous pustulosis after pemetrexed, and recurrence after re-introduction

Bracke, An; Marck, Eric Van; Lambert, Jo

doi:10.1111/j.1365-2230.2008.02902.x

Cited by 24 publications

(17 citation statements)

References 12 publications

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“…24,29) Ishikawa et al reported that the incidence of pemetrexed-induced rash was lower in patients who received supplementary corticosteroids, compared to that in patients who did not receive supplementary corticosteroids, although this difference was not statistically significant (23.5% vs. 36.2%, p=0.17). 24) However, the absence of statistical significance might be related to the relatively low number of patients who were enrolled in that study (n=81). In addition, those authors did not evaluate a cutoff dose or the dosing period.…”

Section: Discussionmentioning

confidence: 98%

“…Pemetrexed is associated with a high incidence of rash, and is occasionally responsible for more severe symptoms, such as acute generalized exanthematous pustulosis 25) and Lyell's syndrome. 26,27) Therefore, it is important to prevent the development of rash and to decrease its severity.…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, no significant differences were observed for all patient characteristics between the groups that did and did not develop pemetrexedinduced rash ( Table 2). The Effect of Supplementary Corticosteroids on Pemetrexed-Induced Rash Because previous studies have reported that 3 d of corticosteroid treatment (including day 1) can effectively ameliorate pemetrexed-induced rash, 3,4,12,22,24) we also investigated the effect of supplementary corticosteroids. The cutoff value was found to be 1.5 mg of dexamethasone based on the ROC curve, which was calculated using the average dosage of the supplementary corticosteroids (area under the curve: 0.63).…”

Section: Patient Characteristicsmentioning

confidence: 99%

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Pemetrexed-Induced Rash May Be Prevented by Supplementary Corticosteroids

Sakurada

Kakiuchi

Tajima

et al. 2015

Biological & Pharmaceutical Bulletin

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Pemetrexed, a chemotherapeutic drug, is highly active in non-small cell lung cancer and malignant pleural mesothelioma. Unfortunately, rashes are more commonly associated with pemetrexed than other chemotherapies, and it is recommended that patients receive corticosteroids (8 mg/d of dexamethasone) for 3 d, including the day of pemetrexed administration (day 1). However, the efficacy of corticosteroids in this context has not been fully verified. In this retrospective study, we evaluated the medical records of 78 patients who received pemetrexed between April 2009 and March 2014, to confirm whether supplementary corticosteroids prevented rash development. The incidence of rash was lower in the 47 patients who received supplementary corticosteroids (after day 1) compared with the incidence among the 31 patients who did not receive supplementary corticosteroids (19.1% vs. 38.7%). The average cutoff dosage of supplementary corticosteroids on day 2 and day 3 was 1.5 mg/d of dexamethasone, as calculated using the receiver operating characteristic curve, and the odds ratio was 0.33 (95% confidence interval: 0.12-0.94). Administration of ≥1.5 mg of corticosteroids on day 2 and day 3 significantly reduced the severity of the rash compared to no supplementary treatment (grades 2/3, 13.3% vs. 33.3%, p<0.05). However, increasing the dose of corticosteroids had no additional effect on rash development. These results suggest that ≥1.5 mg of supplementary dexamethasone on day 2 and day 3 (in addition to day 1) may be necessary for preventing pemetrexed-induced rash, but high doses of dexamethasone (e.g., 8 mg/d) are unnecessary.Key words pemetrexed; rash; dexamethasone; corticosteroid; risk factor Pemetrexed (Alimta, Eli Lilly and Co.) is a novel multitargeted antifolate that inhibits thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase. 1,2) These multiple targets may explain the broad and preferable antitumor activity of pemetrexed, which has been evaluated in non-small cell lung cancer (NSCLC), malignant pleural mesothelioma (MPM), head, neck, cervical, breast, gastric, colorectal, pancreatic, and bladder cancers. [3][4][5][6][7][8][9][10][11][12][13][14] Pemetrexed is currently approved in combination with platinum (cisplatin or carboplatin) as a first-line treatment, and as a single-agent second-line treatment, for MPM and NSCLC. 15,16) Moreover, cisplatin plus pemetrexed provides improved survival and reduced toxicity in patients with non-squamous NSCLC, compared to cisplatin plus gemcitabine. 17) Interestingly, multivariate analysis has revealed that increasing levels of homocysteine and methylmalonic acid are correlated with a toxic increase in pemetrexed. 18) The risks associated with severe pemetrexed toxicity, such as neutropenia, thrombocytopenia, infection, and diarrhea, can be reduced by decreasing homocysteine and methylmalonic acid levels by supplementing patients with folic acid and vitamin B 12 . 18) Unfortunately, rash is one of the most common adverse events that ...

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Patient Characteristicsmentioning

confidence: 99%

See 1 more Smart Citation

Pemetrexed-Induced Rash May Be Prevented by Supplementary Corticosteroids

Sakurada

Kakiuchi

Tajima

et al. 2015

Biological & Pharmaceutical Bulletin

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“…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). In oncological practice, the dose-limiting toxicity (DLT) of pemetrexed is determined by its myelosuppression although certain other non-haematological toxicities may occur before myelosuppression is reached.…”

Section: Cutaneous Adverse Reactionsmentioning

confidence: 99%

“…In some instances, however, CAR identification was more clearly supported (24)(25)(26)(27)(28)(29)(30)(31)(32). The specific diseases associated with these events were reported to be alopecia (22), acute generalized exanthematous pustulosis (AGEP) (24), urticarial vasculitis (25), radiation recall dermatitis (RRD) (26)(27)(28), toxic epidermal necrolysis (TEN) (29,30), eyelid edema (31) and PL-like dermatitis (32).…”

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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Antimetabolite Reactions

Chu¹,

Kong²

2013

Dermatologic Principles and Practice in Oncology

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Acute generalized exanthematous pustulosis after pemetrexed, and recurrence after re-introduction

Cited by 24 publications

References 12 publications

Pemetrexed-Induced Rash May Be Prevented by Supplementary Corticosteroids

Pemetrexed-Induced Rash May Be Prevented by Supplementary Corticosteroids

Revisiting cutaneous adverse reactions to pemetrexed

Antimetabolite Reactions

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