Dados do Trabalho

Título

PROTON PUMP INHIBITORS (PPI) AND PATHOLOGICAL RESPONSE IN RECTAL CANCER: A MULTINATIONAL STUDY

Introdução

A pharmacokinetic drug-drug interaction between proton pump inhibitors (PPI) and capecitabine (Cap) has been proposed, likely due to gastric pH increase and reduced Cap absorption. This combination was associated with inferior oncological outcomes in colorectal, breast and gastric cancers. We aimed to investigate whether such interaction would influence pathological response to chemoradiation (ChRT) with Cap in rectal cancer (RC).

Objetivo

To compare the rates of complete (ypCR) or partial (ypPR) pathological responses between patients (pts) who used or not PPI during neoadjuvant ChRT with Cap for RC. Secondarily, to evaluate these endpoints in a cohort of 5-fluorouracil (5FU).

Método

All consecutive pts with localized rectal adenocarcinoma who received curative intent ChRT with Cap or 5FU followed by surgery were retrospectively included. Total neoadjuvant therapy (TNT) including Cap was allowed. Pathological response was defined by AJCC staging system. Any utilization of PPI concomitant to Cap/5FU was considered. Binary variables were compared with chi-square test. Logistic regression was used for multivariable analysis.

Resultado

From April 2009 to August 2020, 229 pts were included in the Cap cohort. The median age at diagnosis was 58 years; most with comorbidities (60.7%) and ECOG ≥ 1 (62.0%). Rectal tumors were predominantly distal (51.1%), stage III (79.5%), and moderately differentiated (68.6%). TNT was offered to 12.7%. Only 41 pts (17.9%) used PPI: 95.1% primary generation PPI; 73.1% for > 50% of the neoadjuvant time. The rates of ypCR and ypPR were 19.7% and 52.8%, respectively. PPI did not interfere with ypCR or ypCR/ypPR (22.0% vs 19.1%, p=0.67; and 78.0% vs 71.3%, p=0.44), even when excluding the TNT population: 79.5% for PPI vs 68.9% for non-PPI (p=0.24). Only clinical response was associated with improved ypCR or ypCR/ypPR in the multivariable analysis. PPI also did not influence the ypCR and ypCR/ypPR in the 107-pts 5FU cohort (25.0% vs 31.6%; p=0.63; and 92.9% vs 77.2%; p=0.91).

Conclusão

PPI concomitant to Cap/5FU did not influence pathological response in these cohorts of rectal cancer. While further studies are needed, PPI avoidance, for pts with medical recommendation for its use, should be reconsidered in the neoadjuvant treatment of RC.

Palavras-chave

Rectal cancer; drug-drug interactions; capecitabine; proton pump inhibitors

Área

Oncologia - Tumores TGI Inferior (cólon/reto/ânus)