Pemetrexed-induced neutropenic enteritis and severe cutaneous hyperpigmentation in a patient with malignant pleural mesothelioma

Our plain-English summary of Pemetrexed-induced neutropenic enteritis and severe cutaneous hyperpigmentation in a patient with malignant pleural mesothelioma, by K. Buchinger, R. Stahel, V. Niggemeier, et al (Lung Cancer, 2013).

The study

• Authors: K. Buchinger, R. Stahel, V. Niggemeier, C. Gubler, D. Franzen
• Journal: Lung Cancer
• Published: 2013;80(3):347-9
• Cited by: 11 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Neutropenic enteritis (NE) or enterocolitis (NEC) is a rare, but potentially life-threatening side effect of neutropenia-inducing chemotherapy agents. Generally, its occurrence is attributed to leukemia-associated chemotherapies. Two cases of NE have been reported after the appliance of pemetrexed for treatment of non-small cell lung cancers. To our knowledge, NE has never been reported due to treatment with pemetrexed for malignant pleural mesothelioma (MPM). We present a case of MPM in a 77-year-old male suffering from severe NE one week after the seventeenth cycle of pemetrexed in the course of maintenance therapy for MPM, which could be treated successfully with antibiotic coverage and supportive measures. Concomitantly the patient showed a severe hyperpigmentation of his entire integument sparing the palms of both hands and the soles of his feet. After exclusion of alternative causes of skin hyperpigmentation, a pemetrexed-induced cutaneous hyperpigmentation was assumed according to two previous case reports. A combination of both pemetrexed-induced side effects in one patient has not been reported to date.

Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

In plain English

This case report from University Hospital Zurich, Switzerland, described a 77-year-old never-smoking man with stage III malignant pleural mesothelioma. The article did not describe the patient's asbestos exposure. Treatment was carboplatin with pemetrexed, then pemetrexed alone as maintenance. The patient was admitted with severe abdominal pain, weight loss and mild fever that began one week after the seventeenth dose, given at about 420 mg/m2 because of reduced kidney function. A CT scan showed segmental small bowel wall thickening. Three days later the patient developed fever with very low neutrophil (white blood cell) counts. The doctors treated this as neutropenic enteritis, a bowel inflammation linked to low white cell counts, using antibiotics, an antifungal, bowel rest and intravenous feeding. The bowel thickening resolved; the patient moved to rehabilitation after 43 days. The patient's whole skin had turned dark brown over the previous two months, sparing palms and soles. After ruling out other causes, the authors assumed pemetrexed had caused this. The authors concluded that both side effects should be considered after excluding other causes, especially with prolonged pemetrexed use.

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: case report (one patient)
• Who was studied: One 77-year-old never-smoking Caucasian man with stage III malignant pleural mesothelioma, treated at University Hospital Zurich, Switzerland; mesothelioma diagnosed 23 months before this presentation
• Exposure: The chemotherapy drug pemetrexed: three first-line cycles with carboplatin (225 mg/m2) and pemetrexed (500 mg/m2), then single-agent pemetrexed maintenance, with the seventeenth dose reduced to about 420 mg/m2. The article gives no asbestos exposure history for the patient.
• Main results:
  • The patient was admitted to the emergency department with severe, diffuse abdominal pain, weight loss and mild fever; the symptoms began one week after the seventeenth pemetrexed dose
  • An abdominal CT scan showed segmental small bowel wall thickening (5 mm) without involvement of the colon or caecum
  • Three days later the patient developed febrile neutropenia with fever up to 38.6 degrees C, worsening abdominal pain and new diarrhea; no infection was found in blood or stool samples
  • The patient recovered with treatment; a follow-up CT showed the bowel wall thickening had resolved, and after 43 days the patient was transferred to a rehabilitative institution
  • The patient's whole skin showed severe, diffuse hyperpigmentation sparing only the palms and soles; it had begun two months before presentation and was unchanged during the hospital stay
  • Hemochromatosis, adrenal insufficiency and systemic argyria were considered excluded. Of the patient's medicines, only pemetrexed and amiodarone were possible causes, and amiodarone was started after the skin change was first seen. Pemetrexed-induced hyperpigmentation was therefore assumed.
• The authors' conclusion: The authors concluded that pemetrexed-induced neutropenic enteritis and skin hyperpigmentation should both be considered after other causes are excluded, particularly when pemetrexed is given for a prolonged period, even at doses adjusted to kidney function. They also stated that abdominal pain with bowel wall thickening on CT in pemetrexed-treated patients should alert clinicians to possible neutropenic enteritis.

Topics

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

Medical terms in this study, explained in our Lexicon: Pemetrexed (Alimta), Pleural Mesothelioma, Neutropenia, Chemotherapy, Non-Small Cell Lung Cancer.

Related studies

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• Fatal pemetrexed-induced lung injury in patients with advanced mesothelioma: a report of two cases — K. Nagata, R. Kaji, et al. (2010)
• Pemetrexed-induced eyelid edema in lung cancer — P.R. Martins-Filho, S.Y. Kameo, et al. (2013)
• Thymidylate synthase and folyl-polyglutamate synthase are not clinically useful markers of response to pemetrexed in patients with malignant pleural mesothelioma — D.E. Lustgarten, C. Deshpande, et al. (2013)
• Gemcitabine and vinorelbine as second-line or beyond treatment in patients with malignant pleural mesothelioma pretreated with platinum plus pemetrexed chemotherapy — G. Toyokawa, M. Takenoyama, et al. (2014)
• Pemetrexed in the treatment of malignant mesothelioma: results from an expanded access program in Germany — M. Reck, R.A. Stahel, et al. (2010)

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