Drug fever after cancer chemotherapy is most commonly observed on posttreatment days 3 and 4

Our plain-English summary of Drug fever after cancer chemotherapy is most commonly observed on posttreatment days 3 and 4, by D. Ogawara, M. Fukuda, S. Ueno, et al (Supportive Care in Cancer, 2016).

The study

• Authors: D. Ogawara, M. Fukuda, S. Ueno, Y. Ohue, S. Takemoto, K. Mizoguchi, K. Nakatomi, Y. Nakamura, Y. Obase, T. Honda, K. Tsukamoto, K. Ashizawa, M. Oka, S. Kohno
• Journal: Supportive Care in Cancer
• Published: 2016;24(2):615-619
• Cited by: 18 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: This study was undertaken to analyze the characteristics of fever after cancer chemotherapy in order to reduce unnecessary medical care.

Methods: Retrospectively, 1016 consecutive cycles of cancer chemotherapy were analyzed. Fever was defined as a temperature of ≥ 37.5 °C lasting for 1 h. Age, sex, tumor histology, the treatment regimen, the timing of fever onset, the number of days for which the fever persisted, the cause of the fever, the presence or absence of radiotherapy, and the use of granulocyte colony-stimulating factor (G-CSF) were examined.

Results: The patients included 748 males and 268 females (median age = 68, range = 29-88), of whom 949, 52, and 15 were suffering from lung cancer, malignant pleural mesothelioma, and other diseases, respectively. Fever was observed in 367 cycles (36 %), including 280 cycles (37 %) involving males and 87 cycles (32 %) involving females. Fever occurred most commonly in the first cycles and was higher than later cycles (41 vs. 30 %, p < 0.001). Fever occurred most frequently on posttreatment days 4 (8 %), 3 (7 %), and 12 (7 %), and the distribution of fever episodes exhibited two peaks on posttreatment days 3 and 4 and 10-14. Fever on posttreatment days 3 and 4 was most commonly observed in patients treated with gemcitabine (20 %) or docetaxel (18 %). The causes of fever included infection (47 %; including febrile neutropenia [24 %]), adverse drug effects (24 %), unknown causes (19 %), and tumors (7 %). Radiotherapy led to a significant increase in the frequency of fever (46 vs. 34 %, p < 0.001). Thirty-three percent of patients received G-CSF, and the incidence ratios of fever in patients who received G-CSF were higher than those who did not receive G-CSF (44 vs. 31 %, p < 0.001).

Conclusion: The febrile episodes that occurred on posttreatment days 3 and 4 were considered to represent adverse drug reactions after cancer chemotherapy. Physicians should be aware of this feature of chemotherapy-associated fever and avoid unnecessary examination and treatments including prescribing antibiotics.

In plain English

In this retrospective study from two Japanese hospitals, the authors analyzed fever in 1016 consecutive chemotherapy cycles for chest cancers given between 2004 and 2008. Of these, 949 cycles were for lung cancer, 52 for malignant pleural mesothelioma and 15 for other diseases. Asbestos exposure was not studied, and results for mesothelioma were not reported separately. Fever (37.5 °C or higher lasting 1 hour) occurred in 36% of cycles (367 of 1016), more often in first cycles than in later ones. It was most common on posttreatment days 4 (8.3%), 3 (6.8%) and 12 (6.7%). Fever on days 3 and 4 occurred in 11% of cycles, most often with gemcitabine (20%) and docetaxel (18%). Recorded causes were infection (47%), adverse drug reactions (24%), unknown causes (19%) and tumors (7%). Fever was more frequent with radiotherapy (46% vs 34%) and with G-CSF (granulocyte colony-stimulating factor) (44% vs 31%). The authors could not determine whether G-CSF itself caused fever. The authors concluded that fever on days 3 and 4 was considered to represent drug reactions, and that knowing this pattern should help avoid unnecessary tests and antibiotics.

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: retrospective analysis of chemotherapy cycles (hospital records)
• Who was studied: Consecutive admitted patients with thoracic cancers receiving chemotherapy at Kawasaki Medical School Hospital (April 2004 to March 2007) and Nagasaki Municipal Hospital (April 2007 to December 2008), Japan. 1016 chemotherapy cycles in total: 748 involving males and 268 involving females, median age 68 (range 29 to 88). By disease: 949 cycles lung cancer, 52 malignant pleural mesothelioma, 15 others.
• Exposure: Cancer chemotherapy drugs, including gemcitabine, irinotecan, amrubicin, docetaxel, vinorelbine, paclitaxel, carboplatin, gefitinib, etoposide, cisplatin, pemetrexed, nedaplatin and S-1. Radiotherapy and G-CSF use were also examined. Asbestos exposure was not studied.
• Main results:
  • Fever occurred in 36% of all chemotherapy cycles (367 of 1016).
  • Fever was more frequent in first cycles (41%, 236 of 576) than in later cycles; the difference was statistically significant (p less than 0.001).
  • Fever was most common on posttreatment day 4 (8.3%), day 3 (6.8%) and day 12 (6.7%).
  • Fever on posttreatment days 3 and 4 occurred in 11% of all cycles (113 of 1016).
  • Among drugs used in 30 or more cases, fever on days 3 and 4 was most common with gemcitabine (20%), followed by docetaxel (18%).
  • Of fever episodes, causes were infection (47%), adverse drug reactions (24%), unknown causes (19%) and tumors (7%). Febrile neutropenia made up 50% of the infection-derived fevers.
  • Fever was more frequent among those treated with radiotherapy than without (46% vs 34%, p = 0.001).
  • Among 909 patients analyzed for G-CSF use, fever occurred in 44% (134/303) of those who received G-CSF and 31% (188/606) of those who did not (p less than 0.001).
  • There was no statistically significant difference in fever frequency between the sexes (p = 0.146) or by age (p = 0.424).
• The authors' conclusion: The authors considered the fever peak on posttreatment days 3 and 4 to be due to adverse drug reactions. They concluded that knowledge of this pattern should help prevent unnecessary examinations and treatments, including antibiotics.
• Limitations the authors state:
  • The authors could not determine whether G-CSF itself contributed to fever, because fever caused by G-CSF is hard to distinguish from fever caused by neutropenia.

Topics

Medical terms in this study, explained in our Lexicon: Chemotherapy, Histology, Lung Cancer, Pleural Mesothelioma, Gemcitabine, Neutropenia.

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