Adverse reactions of targeted therapy in cancer patients: a retrospective study of hospital medical data in China

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Abstract

Background

The adverse reactions (ADRs) of targeted therapy were closely associated with treatment response, clinical outcome, quality of life (QoL) of patients with cancer. However, few studies presented the correlation between ADRs of targeted therapy and treatment effects among cancer patients. This study was to explore the characteristics of ADRs with targeted therapy and the prognosis of cancer patients based on the clinical data.

Methods

A retrospective secondary data analysis was conducted within an ADR data set including 2703 patients with targeted therapy from three Henan medical centers of China between January 2018 and December 2019. The significance was evaluated with chi-square test between groups with or without ADRs. Univariate and multivariate logistic regression with backward stepwise method were applied to assess the difference of pathological characteristics in patients with cancer. Using the univariate Cox regression method, the actuarial probability of overall survival was performed to compare the clinical outcomes between these two groups.

Results

A total of 485 patients were enrolled in this study. Of all patients, 61.0% ( n = 296) occurred ADRs including skin damage, fatigue, mucosal damage, hypertension and gastrointestinal discomfort as the top 5 complications during the target therapy. And 62.1% of ADRs were mild to moderate, more than half of the ADRs occurred within one month, 68.6% ADRs lasted more than one month. Older patients ( P = 0.022) and patients with lower education level ( P = 0.036), more than 2 comorbidities ( P = 0.021), longer medication time ( P = 0.022), drug combination ( P = 0.033) and intravenous administration ( P = 0.019) were more likely to have ADRs. Those with ADRs were more likely to stop taking ( P = 0.000), change ( P = 0.000), adjust ( P = 0.000), or not take the medicine on time ( P = 0.000). The number of patients with recurrence ( P = 0.000) and metastasis ( P = 0.006) were statistically significant difference between ADRs and non-ADRs group. And the patients were significantly poor prognosis in ADRs groups compared with non-ADRs group.

Conclusion

The high incidence of ADRs would affect the treatment and prognosis of patients with cancer. We should pay more attention to these ADRs and develop effective management strategies.

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Most cited references 34

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Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

Ahmedin Jemal, Lindsey A Torre, Rebecca Siegel … (2018)

This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1-31. © 2018 American Cancer Society.

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Kinase-targeted cancer therapies: progress, challenges and future directions

Khushwant S Bhullar, Naiara Lagarón, Eileen M. McGowan … (2018)

The human genome encodes 538 protein kinases that transfer a γ-phosphate group from ATP to serine, threonine, or tyrosine residues. Many of these kinases are associated with human cancer initiation and progression. The recent development of small-molecule kinase inhibitors for the treatment of diverse types of cancer has proven successful in clinical therapy. Significantly, protein kinases are the second most targeted group of drug targets, after the G-protein-coupled receptors. Since the development of the first protein kinase inhibitor, in the early 1980s, 37 kinase inhibitors have received FDA approval for treatment of malignancies such as breast and lung cancer. Furthermore, about 150 kinase-targeted drugs are in clinical phase trials, and many kinase-specific inhibitors are in the preclinical stage of drug development. Nevertheless, many factors confound the clinical efficacy of these molecules. Specific tumor genetics, tumor microenvironment, drug resistance, and pharmacogenomics determine how useful a compound will be in the treatment of a given cancer. This review provides an overview of kinase-targeted drug discovery and development in relation to oncology and highlights the challenges and future potential for kinase-targeted cancer therapies.

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Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs.

Mark Kris, Bruce Johnson, Lynne D Berry … (2014)

Targeting oncogenic drivers (genomic alterations critical to cancer development and maintenance) has transformed the care of patients with lung adenocarcinomas. The Lung Cancer Mutation Consortium was formed to perform multiplexed assays testing adenocarcinomas of the lung for drivers in 10 genes to enable clinicians to select targeted treatments and enroll patients into clinical trials. To determine the frequency of oncogenic drivers in patients with lung adenocarcinomas and to use the data to select treatments targeting the identified driver(s) and measure survival. From 2009 through 2012, 14 sites in the United States enrolled patients with metastatic lung adenocarcinomas and a performance status of 0 through 2 and tested their tumors for 10 drivers. Information was collected on patients, therapies, and survival. Tumors were tested for 10 oncogenic drivers, and results were used to select matched targeted therapies. Determination of the frequency of oncogenic drivers, the proportion of patients treated with genotype-directed therapy, and survival. From 2009 through 2012, tumors from 1007 patients were tested for at least 1 gene and 733 for 10 genes (patients with full genotyping). An oncogenic driver was found in 466 of 733 patients (64%). Among these 733 tumors, 182 tumors (25%) had the KRAS driver; sensitizing EGFR, 122 (17%); ALK rearrangements, 57 (8%); other EGFR, 29 (4%); 2 or more genes, 24 (3%); ERBB2 (formerly HER2), 19 (3%); BRAF, 16 (2%); PIK3CA, 6 (<1%); MET amplification, 5 (<1%); NRAS, 5 (<1%); MEK1, 1 (<1%); AKT1, 0. Results were used to select a targeted therapy or trial in 275 of 1007 patients (28%). The median survival was 3.5 years (interquartile range [IQR], 1.96-7.70) for the 260 patients with an oncogenic driver and genotype-directed therapy compared with 2.4 years (IQR, 0.88-6.20) for the 318 patients with any oncogenic driver(s) who did not receive genotype-directed therapy (propensity score-adjusted hazard ratio, 0.69 [95% CI, 0.53-0.9], P = .006). Actionable drivers were detected in 64% of lung adenocarcinomas. Multiplexed testing aided physicians in selecting therapies. Although individuals with drivers receiving a matched targeted agent lived longer, randomized trials are required to determine if targeting therapy based on oncogenic drivers improves survival. clinicaltrials.gov Identifier: NCT01014286.

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Author and article information

Contributors

Ruofei Du: ruofei2007666@163.com

Xin Wang: wangxin628@zzu.edu.cn

Changying Chen:

ORCID: https://orcid.org/0000-0003-2151-7351

changying@zzu.edu.cn

Tao Wang: wangtaomary@zzu.edu.cn

Journal

Journal ID (nlm-ta): BMC Cancer

Journal ID (iso-abbrev): BMC Cancer

Title: BMC Cancer

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2407

Publication date (Electronic): 28 February 2021

Publication date PMC-release: 28 February 2021

Publication date Collection: 2021

Volume: 21

Electronic Location Identifier: 206

Affiliations

[1 ]GRID grid.207374.5, ISNI 0000 0001 2189 3846, The College of Nursing and Health of Zhengzhou University, ; Zhengzhou, 450001 China

[2 ]GRID grid.412633.1, The First Affiliated Hospital of Zhengzhou University, ; Zhengzhou, 450052 China

[3 ]GRID grid.207374.5, ISNI 0000 0001 2189 3846, School of Medical Sciences, , Zhengzhou University, ; Zhengzhou, 450001 China

[4 ]GRID grid.464343.2, ISNI 0000 0000 9153 2950, School of Statistics, , Henan University of Economics and Law, ; Zhengzhou, 450046 China

[5 ]GRID grid.1025.6, ISNI 0000 0004 0436 6763, Centre for Comparative Genomics, , Murdoch University, ; Perth, WA 6150 Australia

[6 ]Hebi People’s Hospital, Hebi, 458030 China

Author information

Changying Chen https://orcid.org/0000-0003-2151-7351

Article

Publisher ID: 7946

DOI: 10.1186/s12885-021-07946-x

PMC ID: 7916285

PubMed ID: 33639888

SO-VID: cad3f59a-08e9-4284-86c3-8437cc891bf0

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 2 September 2020

Date accepted : 21 February 2021

Funding

Funded by: The National Natural Science Foundation of China

Award ID: 81773175

Award Recipient : Tao Wang

Funded by: China Postdoctoral Science Foundation in 2018:

Award ID: 2018M630839

Award Recipient : Tao Wang

Custom metadata

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: adverse reactions,cancer patients,hospitalization,targeted therapy,quality of life

Data availability:

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: adverse reactions, cancer patients, hospitalization, targeted therapy, quality of life

Adverse reactions of targeted therapy in cancer patients: a retrospective study of hospital medical data in China

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Abstract

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Conclusion

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Karger: Oncology

Most cited references 34

Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

Kinase-targeted cancer therapies: progress, challenges and future directions

Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs.

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