Continuous Low-Dose versus Standard-Dose Capecitabine Monotherapy as Second/Third-Line Chemotherapy for Metastatic Gastrointestinal Malignancies: A Retrospective Multicenter Analysis

BackgroundCapecitabine monotherapy is frequently employed as second/third-line treatment for metastatic gastrointestinal malignancies. Standard dosing often produces severe toxicities incompatible with palliative care principles. This study compared continuous low-dose (CLD) versus standard-dose (StD) capecitabine in the palliative setting. MethodsAfter at least one prior line of chemotherapy, 33 and 45 patients received StD (1.0-1.25 g/m2 bid on days 1-14 of a 21-day cycle) and CLD (500 mg bid daily without interruption) capecitabine, respectively, between March 2013 and August 2016 for metastatic gall bladder (n=51), pancreatic (n=14), and gastric (n=13) cancers. Toxicity and treatment discontinuation rates were compared using Fishers Exact Test. Progression-free survival (PFS) and overall survival (OS) were compared using the Mann-Whitney U test. ResultsGrade [&ge;]3 toxicity was significantly higher in StD versus CLD (57.6% vs 4.4%; p<0.001). Treatment discontinuation due to toxicity was higher in StD versus CLD (66.7% vs 2.2%; p<0.001). Grade 5 toxicity occurred in 3 patients (9.1%) in the StD arm versus 0 in the CLD arm. Median PFS was 90 days (StD) versus 119 days (CLD; p=0.018). Median OS was 160 days (StD) versus 181 days (CLD; p=0.085). Disease stabilization was more common in CLD (51.1% vs 54.5%), while progression-free survival was prolonged. ConclusionsWhile lower toxicities and discontinuation rates were expected in the CLD arm, the superior PFS and comparable OS with substantially reduced toxicity were striking. The metronomic low-dose approach provides a more favorable balance between disease control and tolerability in palliative gastrointestinal cancer therapy. Further prospective randomized trials are warranted.