Retrospective study of hypersensitivity reactions to chemotherapeutic agents in a thoracic oncology service

Our plain-English summary of Retrospective study of hypersensitivity reactions to chemotherapeutic agents in a thoracic oncology service, by H. Capelle, C. Tummino, L. Greillier, et al (Journal of Clinical Pharmacy and Therapeutics, 2018).

The study

• Authors: H. Capelle, C. Tummino, L. Greillier, M. Gouitaa, J. Birnbaum, N. Ausias, F. Barlesi, M. Montana
• Journal: Journal of Clinical Pharmacy and Therapeutics
• Published: 2018;43(3):320-326
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

What Is Known And Objective: With the increasing use of cancer chemotherapy agents, hypersensitivity reactions are commonly encountered. The allergic clinical symptoms are variable and unpredictable. The aim of this study was to identify the characteristics of hypersensitivity reactions and to assess the value of skin tests for platinum salts and pemetrexed in the treatment of patients with non-small cell lung cancers or malignant pleural mesothelioma.

Methods: A single-centre retrospective study was performed for 2 years. Patients treated with the drugs of interest for an advanced or metastatic non-small cell lung cancers or malignant pleural mesothelioma and who experienced hypersensitivity reactions symptoms were eligible for this study. Clinical symptoms of hypersensitivity reactions, population characteristics and administered chemotherapy regimens were identified.

Results: The hypersensitivity reactions frequency was rare (1.2%) and concerned 17 patients in our study. Typical clinical features of immediate hypersensitivity reactions associated with treatment were observed for nine patients (anaphylactic reactions for three cases, angioedema and hypotension associated with asthenia and heat in one case, respectively, and other cutaneous symptoms in the remaining four cases). Skin tests were positive in three patients, but only for platinum salts. The outcome after reintroduction of a negatively tested platinum salt allowed us to calculate a negative predictive value for platinum salt skin tests of 100%. For pemetrexed, skin tests were negative for all patients.

What Is New And Conclusion: Skin tests could be used to diagnose hypersensitivity reactions with platinum salts or to evaluate the possibility of cross-reactions between two platinum salts. A negative skin test may predict with reasonable reliability the absence of future hypersensitivity reactions in case of reintroduction of drug infusion. Because the IgE-mediated mechanism has never been demonstrated for pemetrexed, skin tests are not valid and have no diagnostic value for this molecule. Because hypersensitivity reactions are potentially fatal adverse events, we recommend that patients who experience a hypersensitivity reactions onset should be monitored closely and clinicians must be aware of hypersensitivity reaction signs.

© 2017 John Wiley & Sons Ltd.

In plain English

This single-centre retrospective study from a thoracic oncology service in Marseille, France, examined hypersensitivity (allergic-type) reactions to chemotherapy in patients treated for advanced or metastatic non-small cell lung cancer or malignant pleural mesothelioma with cisplatin- or carboplatin-based combinations, or pemetrexed alone. The article does not say how many patients had mesothelioma and does not address asbestos. From January 2011 to July 2013, 17 patients had reactions, which the authors reported as 1.2% of treated patients. In nine, symptoms began within an hour of infusion and a platinum drug was suspected; three of these were anaphylactic reactions. Skin tests, done in 15 patients, were positive in three, only for platinum drugs. After a negatively tested platinum drug was given again, the authors calculated a negative predictive value of 100% for platinum skin tests. The authors described pemetrexed skin tests as negative for all tested patients, although one intradermal test was doubtful when read 24 hours later. The authors concluded that platinum skin tests could help diagnose reactions, while pemetrexed skin tests have no diagnostic value. They noted the small, retrospective design.

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: Single-centre retrospective study of patients referred for skin testing after chemotherapy hypersensitivity reactions
• Who was studied: 17 patients with hypersensitivity reaction signs, treated between January 2011 and July 2013 in the Thoracic Oncology Service of a university teaching hospital in Marseille, France, for advanced or metastatic non-small cell lung cancer or malignant pleural mesothelioma. Patients in clinical trials were excluded. The number with mesothelioma is not reported.
• Exposure: Chemotherapy: cisplatin- and carboplatin-based doublet regimens, or second-line pemetrexed alone. Skin prick and intradermal tests were done with these drugs. The study does not concern asbestos exposure.
• Main results:
  • 1.2% of treated patients had a hypersensitivity reaction (17 patients). The article does not give the total number treated.
  • In nine patients, symptoms began within the first hour after the infusion started, and platinum salts were suspected.
  • Among the nine immediate reactions, three were anaphylactic reactions.
  • Pemetrexed was suspected in five delayed reactions.
  • Median number of courses before a reaction: two cycles (range 1 to 4) for platinum salts and 2.5 cycles (range 1 to 22) for pemetrexed.
  • Skin or cutaneous manifestations, or angioedema, developed in 12 of the 17 patients.
  • Skin tests were performed in 15 of the 17 patients. The median time between reaction and testing was 4 weeks (range 2 to 104 weeks).
  • Skin tests were positive in three patients, only for platinum salts. One case of cross-hypersensitivity between cisplatin and carboplatin (patient 5) led to chemotherapy being stopped.
  • Two patients with positive cisplatin tests and negative carboplatin tests were switched to carboplatin. No adverse drug reaction was observed, and treatment continued.
  • Negative predictive value of platinum salt skin tests was 100%. The positive predictive value could not be calculated.
  • The authors described pemetrexed skin tests as negative for all tested patients after a delayed reaction. One intradermal test (patient 6) was doubtful on the delayed reading 24 hours later. That patient had a recurrence of a mild reaction when pemetrexed was given again.
• The authors' conclusion: The authors concluded that skin tests could be used to diagnose hypersensitivity reactions to platinum salts or to evaluate cross-reactions between two platinum salts, and that a negative test may predict with reasonable reliability that a reaction will not recur. Because an IgE-mediated mechanism has never been shown for pemetrexed, they concluded that skin tests are not valid and have no diagnostic value for that drug. They called for further work to confirm the usefulness of skin tests.
• Limitations the authors state:
  • The study was retrospective and had a small number of patients; the authors suggested a larger prospective study.
  • Skin tests were done sooner after the reaction than the recommended 4 to 6 weeks, which may explain the relatively low rate of positive tests.

Topics

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

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