Low-Cost Genetic and Clinical Predictors of Response and Toxicity of Platinum-Based Chemotherapy in Advanced Non-Small Cell Lung Cancer

Author:

Spasic Jelena1ORCID,Cavic Milena2ORCID,Stanic Nemanja1ORCID,Zaric Bojan34,Kovacevic Tomi34,Radosavljevic Davorin1,Nagorni-Obradovic Ljudmila56

Affiliation:

1. Clinic for Medical Oncology, Institute for Oncology and Radiology of Serbia, Serbia

2. Department of Experimental Oncology, Institute for Oncology and Radiology of Serbia, Serbia

3. Faculty of Medicine, University of Novi Sad, Serbia

4. Institute for Pulmonary Diseases of Vojvodina, Serbia

5. Faculty of Medicine, University of Belgrade, Serbia

6. Clinic for Pulmonology, University Clinical Centre of Serbia, Serbia

Abstract

Background This study aimed to evaluate for the first time whether certain genetic and clinical factors could serve as minimally invasive predictors of survival and toxicity to platinum-based chemotherapy in advanced lung adenocarcinoma. Methods The study included 121 advanced lung adenocarcinoma patients treated with platinum-based dublets until progression or unacceptable toxicity. Response was evaluated using standard radiological methods and toxicity graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Genotyping was performed using PCR-RFLP. Statistical significance was set at P < .05. Results No significant influence of the examined polymorphisms on the occurrence of high-grade toxicity was detected. However, TP53 72Pro allele carriers were more prone to nausea (P = .037) and thrombocytopenia (P = .051). Anemia and neuropathy occurred more frequently in XRCC1 399Arg allele carriers (Pearson χ2 test, P = .025 and P = .004 respectively). RAD51 135CC carriers were significantly more prone to neutropenia (P = .027). Conclusions A set of easily determined genetic and clinical predictors of survival and specific toxicity profiles of platinum-based chemotherapy in advanced lung adenocarcinoma were determined in this study, which might be useful for the construction of population-specific, time- and cost-efficient prognostic and predictive algorithms.

Funder

Ministry of Education, Science and Technological Development

MSCA-RISE, Horizon 2020 - Research and Innovation Framework Programme, European Commision

Publisher

SAGE Publications

Subject

Chemical Health and Safety,Health, Toxicology and Mutagenesis,Public Health, Environmental and Occupational Health,Toxicology

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