Estudio observacional retrospectivo sobre interacciones farmacológicas en pacientes con cáncer de mama en tratamiento adyuvante o neoadyuvante

Résumé

Breast cancer patients treated with adjuvant/neoadjuvant chemotherapy have a high risk of interactions between chemotherapy and/or other drugs used concurrently. These drug-drug interactions (DDIs) can influence the effectiveness and toxicity of treatments. Their knowledge and systematic assessment could improve patient care. Objectives: To determine the prevalence of potential DDIs clinically relevant and associated risk factors. To describe the most frequent DDIs and to propose pharmacological alternatives or risk reduction strategies. Secondary objectives: To describe the toxicity and effectiveness related to treatment and the relationship with detected DDIs. According to the findings, to determine possible correlations between specific DDIs and toxicities. Methodology: A retrospective, observational and descriptive study of all patients with breast cancer, who started treatment with adjuvant/neoadjuvant chemotherapy between 01/01/2013 and 12/31/2014. The study included all chemotherapy medications, supportive care drugs and other drugs received by patient during chemotherapy administration. Lexicomp¿ database was used, recording all potential DDIs (classified with a level of risk C, D or X), degree of severity, level of evidence, the mechanism of action, and the description of the potential effect. A descriptive analysis was conducted of the demographic, clinical and analytical data, the drugs prescribed and the potential DDIs detected. Logistic and linear regression models were used to identify risk factors associated with presence and number of potential DDIs. Results: Treatment was initiated by 273 patients, 271 (99.27%) women. A total of 2,842 drugs were prescribed. The total number of detected potential DDIs was 2,287, with a median of 5 [4-10] DDIs per patient. Of all DDIs detected, 1,723 were classified as level of risk C, 496 as level D and 68 as level X. The prevalence of potential DDIs was 100%, 89% for DDIs classified as severe and 14.65% for contraindicated DDIs. Given their potential severity, we would like to highlight the DDIs between metamizole and antineoplastics. Due to the frequency of onset, QT interval prolongation, especially the combination of ondansetron and Selective serotonin reuptake inhibitors (SSRIs). Antidepressants were involved in multiple interactions: QT interval prolongation, extrapyramidal symptoms, serotonin syndrome, neuroleptic malignant syndrome and cytochrome drug interaction. Acetaminophen or ibuprofen were identified as options with lower DDIs risk than metamizole, and palonosetron, sertraline and paroxetine decreased QT interval prolongation risk. On multivariate analysis, were associated with number of antineoplastics and supportive care drugs an increased risk of level D DDIs, and with number of supportive care and other drugs an increased risk of level X DDIs. These issues noted above argue for focusing on this drugs, reviewing usual treatment protocols for supportive care drugs and making individual patient treatment analysis for the other drugs. The median progression-free survival (PFS) and overall survival (OS) was not reached during the study period. Hematological toxicity and taxane-induced peripheral neuropathy were the most frequency toxicity. No correlation could be established between DDIs detected and global or specific toxicities.