Assuntos
Neoplasias da Mama , Inibidores da Bomba de Prótons , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Interações Medicamentosas , Feminino , Humanos , Piperazinas , Inibidores da Bomba de Prótons/farmacologia , Inibidores da Bomba de Prótons/uso terapêutico , Piridinas/farmacologia , Piridinas/uso terapêuticoRESUMO
BACKGROUND: Proton-pump-inhibitors (PPIs) are frequently prescribed for the management of anticancer drug-related gastrointestinal symptoms. Palbociclib is a weak base with pH-dependent solubility and potential drug-drug interaction at the absorption level may affect clinical pharmacokinetics. The current study was aimed at investigating the effect of co-administration of PPIs and palbociclib on progression-free survival (PFS) in metastatic breast cancer (mBC) patients. PATIENTS AND METHODS: Patients affected by estrogen receptor-positive, human epidermal growth factor receptor 2-negative mBC, who were candidates for first-line treatment with palbociclib, were enrolled in this retrospective observational study. Patients were defined as 'no concomitant PPIs' if no PPIs were administered during palbociclib treatment, and as 'concomitant PPIs' if the administration of PPIs covered the entire or not less than two-thirds of treatment with palbociclib. All clinical interventions were made according to clinical practice. RESULTS: A total of 112 patients were enrolled in the study; 56 belonged to the 'no concomitant PPIs' group and 56 to the 'concomitant PPIs' group. Seventy-one patients were endocrine-sensitive and received palbociclib and letrozole, and 43 were endocrine-resistant and were treated with palbociclib and fulvestrant. The most prescribed PPI was lansoprazole. Patients taking PPIs had a shorter PFS than those taking palbociclib and endocrine therapy alone (14.0 versus 37.9 months, P < 0.0001). Multivariate analysis confirmed concomitant PPIs as the only independent predictive factor for shorter PFS (P = 0.0002). PFS was significantly longer in estrogen-sensitive mBC with no concomitant PPIs compared with patients taking PPIs or estrogen-resistant patients, with and without PPIs (P < 0.0001). No correlation with adverse events was found when considering grade >2 hematological toxicities [Common Terminology Criteria for Adverse Events (CTCAE) scale]. CONCLUSIONS: The present study demonstrates that concomitant use of PPIs in mBC patients treated with palbociclib has a detrimental effect on PFS. Therefore, it is recommended to prescribe PPIs with caution in these patients, strictly adhering to the indications in the summary of product characteristics (RCP).
Assuntos
Neoplasias da Mama , Preparações Farmacêuticas , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Interações Medicamentosas , Feminino , Humanos , Piperazinas , Inibidores da Bomba de Prótons/uso terapêutico , Piridinas , Receptores de Estrogênio/uso terapêuticoRESUMO
INTRODUCTION: The present analysis aims to evaluate the consequences of a 2-month interruption of mammographic screening on breast cancer (BC) stage at diagnosis and upfront treatments in a region of Northern Italy highly affected by the severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) virus. METHODS: This retrospective single-institution analysis compared the clinical pathological characteristics of BC diagnosed between May 2020 and July 2020, after a 2-month screening interruption, with BC diagnosed in the same trimester of 2019 when mammographic screening was regularly carried out. RESULTS: The 2-month stop in mammographic screening produced a significant decrease in in situ BC diagnosis (-10.4%) and an increase in node-positive (+11.2%) and stage III BC (+10.3%). A major impact was on the subgroup of patients with BC at high proliferation rates. Among these, the rate of node-positive BC increased by 18.5% and stage III by 11.4%. In the subgroup of patients with low proliferation rates, a 9.3% increase in stage III tumors was observed, although node-positive tumors remained stable. Despite screening interruption, procedures to establish a definitive diagnosis and treatment start were subsequently carried out without delay. CONCLUSION: Our data showed an increase in node-positive and stage III BC after a 2-month stop in BC screening. These findings support recommendations for a quick restoration of BC screening at full capacity, with adequate prioritization strategies to mitigate harm and meet infection prevention requirements.