Alternate-day Capecitabine Plus Trastuzumab for Frail HER2-positive Gastric Cancer: A Pilot Case Series

Patients who are frail with advanced gastric cancer often have a limited tolerance to standard daily chemotherapy, resulting in restricted treatment options. Although alternate-day administration of S-1 has been reported as a low-burden strategy, to the best of our knowledge, the feasibility of alternate-day capecitabine administration has not been evaluated clinically. This study assessed the feasibility and tolerability of alternate-day capecitabine administration in patients with advanced gastric cancer who were frail or pre-frail.

Six patients who were frail or pre-frail with histologically confirmed advanced gastric cancer were retrospectively analyzed. Frailty was assessed using the Vulnerable Elders Survey-13 (VES-13), with scores of 2 and ≥3 defined as pre-frail and frail, respectively. Capecitabine was administered at a standard daily dose of 2,000 mg/m² on alternate days during days 1-14 of a 21-day cycle, with regimen components (oxaliplatin and/or trastuzumab) selected according to the clinical condition and human epidermal growth factor receptor 2 (HER2) status.

The median age was 77 years, and the VES-13 scores ranged from 2 to 7. The overall response rate was 33%, and the disease control rate was 83%. The median overall survival was 11 months, with two patients surviving for over 24 months. The cumulative dose of capecitabine delivered was approximately 57% of that obtained with standard daily administration. Hematologic toxicities included one case each of grade 3 febrile neutropenia and grade 4 anemia, whereas nonhematologic toxicities were mostly grades 1-2. No treatment-related deaths occurred.

Alternate-day capecitabine without a reduction in the daily dose is a feasible treatment modification option, including in combination with trastuzumab, for managing patients with HER2-positive gastric cancer who are frail or pre-frail.