Discussion
toxicity, cancer, HER2-negative AGC, geriatric syndrome
GASTRIC CANCER, CANCER, DISEASE, ONCOLOGY
It is conventional wisdom that older patients are frail and suffer from various comorbidities, such as low renal function. Although a combination of a platinum-based agent and a fluorouracil-based agent is regarded as an acceptable first-line chemotherapy regimen for patients with HER2-negative AGC in the sixth edition of the Japanese Gastric Cancer Treatment Guidelines, the optimal regimen for older patients has not been fully elucidated [S-1 is an oral 5-fluorouracil (5-FU) anti-tumor drug widely used in Japan due to its outpatient convenience and mild toxicity. Several meta-analyses have reported that S-1 and capecitabine could be used in mono- and combination therapy for AGC [In our study, the median OS, PFS, and TTF among all patients were 12.9 (95% CI 11.6–14.8), 5.7 (95% CI 5.0–7.0), and 4.3 (95% CI 3.9–5.7) months, respectively, and the primary endpoint was met. In the reduced-dose group, the median OS, PFS, and TTF were 12.8 (95% CI 11.3–15.3), 5.7 (95% CI 4.4–7.0), and 4.1 (95% CI 3.7–5.7) months, respectively, and were relatively equivalent to those in the original-dose group. Moreover, the incidence of severe hematologic toxicity and elevated creatinine levels in the reduced-dose group was lower than in the original-dose group, suggesting that reduced-dose CapeOX is more suitable for older patients than original-dose CapeOX.Several studies on CapeOX for older patients with AGC have been conducted. A phase II study reported a median OS of 9.8–10.0 months, a median PFS of 5.6–6.0 months, and an ORR of 48.9–51.2% [This study has several limitations. First, the single-arm phase II study design might limit the results to being exploratory. However, to our knowledge, this is the first prospective clinical trial for CapeOX among older patients with AGC in Japan. Second, following the ATTRACTION-4 and CheckMate 649 trials, nivolumab plus chemotherapy is now the standard first-line chemotherapy [Older cancer patients often exhibit decreased physical function, multiple comorbidities, and geriatric syndrome, so it is important to assess individual variability when weighing the risks and benefits of treatment. However, data on vulnerable older patients is limited, as the clinical trials for the development of the standard treatment have enrolled only a subset of older patients in good health who met the eligibility criteria. The method of evaluating the physical, mental, and social functions of patients, in addition to disease evaluation, is designated comprehensive geriatric assessment (CGA). The International Society of Geriatric Oncology recommends the use of CGA when assessing older patients with cancer to detect unaddressed problems and improve their functional status and possibly their survival [