[Evaluation of the Leftover Capecitabine Tablets in Adjuvant CAPOX Chemotherapy for Gastric Cancer].

Since it is important that patients take their oral anticancer therapy as prescribed, pharmacists need to assess adherence. In addition, oral anticancer drugs are expensive, and reuse of leftover drugs at outpatient pharmacy clinics is useful in reducing drug costs. The present study aimed to clarify when and why patients have leftover capecitabine tablets, and the cost of leftover capecitabine tablets reused at an outpatient pharmacy clinic, focusing on adjuvant capecitabine plus oxaliplatin (CAPOX) chemotherapy for gastric cancer. We retrospectively studied patients who received adjuvant CAPOX chemotherapy for gastric cancer between November 1, 2015, and April 30, 2021, at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research. The cost of leftover capecitabine reused by pharmacists was calculated based on the National Health Insurance drug price standard for the study period. This study included 64 patients who received adjuvant CAPOX chemotherapy. Thirty-seven patients had 152 leftover capecitabine tablets. The most common reasons for leftover capecitabine tablets were nausea and vomiting (21.7%), missed doses (18.4%), and diarrhea (13.2%). The leftover capecitabine tablets for 25 patients were reused at the outpatient pharmacy clinic at a cost of JPY 604142.8 (JPY 24165.7 per patient). The study results suggest that evaluating capecitabine adherence and the reasons for leftover capecitabine tablets at outpatient pharmacy clinics as well as reusing leftover medication can contribute to reducing drug costs.

Adjuvant capecitabine plus oxaliplatin after D2 gastrectomy in Japanese patients with gastric cancer: a phase II study.

BACKGROUND: Adjuvant chemotherapy with XELOX (capecitabine plus oxaliplatin) has been shown to be beneficial following resection of gastric cancer in South Korean, Chinese, and Taiwanese patients. This phase II study (J-CLASSIC-PII) was undertaken to evaluate the feasibility of XELOX in Japanese patients with resected gastric cancer. METHODS: Patients with stage II or III gastric cancer who underwent curative D2 gastrectomy received adjuvant XELOX (eight 3-week cycles of oral capecitabine, 1000 mg/m2 twice daily on days 1-14, plus intravenous oxaliplatin 130 mg/m2 on day 1). The primary endpoint was dose intensity. Secondary endpoints were safety, proportion of patients completing treatment, and 1-year disease-free survival (DFS) rate. RESULTS: One hundred patients were enrolled, 76 of whom completed the study as planned. The mean dose intensity was 67.2 % (95 % CI, 61.9-72.5 %) for capecitabine and 73.4 % (95 % CI, 68.4-78.4 %) for oxaliplatin, which were higher than the predefined age-adjusted threshold values of 63.4 % and 69.4 %, respectively, and the study therefore met its primary endpoint. The 1-year DFS rate was 86 % (95 % CI, 77-91 %). No new safety signals were identified. CONCLUSIONS: The feasibility of adjuvant XELOX in Japanese patients with resected gastric cancer is similar to that observed in South Korean, Chinese, and Taiwanese patients in the Capecitabine and Oxaliplatin Adjuvant Study in Stomach Cancer (CLASSIC) study. Based on findings from this study and the CLASSIC study, the XELOX regimen can be considered an adjuvant treatment option for Japanese gastric cancer patients who have undergone curative resection.

Exploratory phase II trial in a multicenter setting to evaluate the clinical value of a chemosensitivity test in patients with gastric cancer (JACCRO-GC 04, Kubota memorial trial).

BACKGROUND: Although postoperative adjuvant chemotherapy with S-1, an oral fluoropyrimidine, has become a standard of care for gastric cancer in Japan, nonresponders may suffer from the cost and adverse reactions without clinical benefit. This multicenter exploratory phase II trial was conducted to see whether a chemosensitivity test, the collagen gel droplet embedded culture drug sensitivity test (CD-DST), can adequately select patients for chemotherapy. METHODS: The CD-DST using four different concentrations of 5-fluorouracil was conducted with resected specimens from preregistered patients who underwent gastrectomy with D2 or more extensive lymphadenectomy. Patients who were histopathologically confirmed to have stage II or greater disease without distant metastasis were eligible for final enrollment. All patients underwent protocol-specified adjuvant chemotherapy with S-1. Three-year relapse-free survival was compared between patients determined as sensitive by the CD-DST (responders) and those deemed insensitive (nonresponders). Appropriate cutoff values for in vitro growth inhibition were defined when the hazard ratio for relapse in responders and the log-rank P values were at their minimum. RESULTS: Of the 311 patients enrolled, 14 were ineligible and 27 failed to start the protocol treatment. The CD-DST failed in 64 other patients, and survival analyses were conducted with the remaining 206 patients (39 stage II disease, 155 stage III disease, and 12 stage IV disease). The outcome of patients who were determined to be responders was significantly superior to that of nonresponders regardless of the 5-fluorouracil concentrations, although no differences in clinicopathologic characteristics were observed between the two groups, except for age. CONCLUSIONS: The CD-DST identified those who benefit from adjuvant chemotherapy. It deserves further evaluation in the setting of a prospective randomized trial. ClinicalTrials.gov identifier: NCT00287755.

How do we apply adjuvant FOLFOX to Japanese patients with curatively resected colorectal cancer?

AIM: In Japan the combination of fluorouracil (5-FU), leucovorin and oxaliplatin (FOLFOX) was approved as adjuvant therapy for stage III or high-risk stage II colon cancer only in September 2009. In this study we evaluated the safety and efficacy of FOLFOX as adjuvant chemotherapy for stage IIIb or IV colorectal cancer (CRC) patients in a Japanese group at a single institute. METHODS: A total of 45 consecutive patients received 12 cycles of adjuvant FOLFOX for stage IIIb (n = 31) or IV (n = 14) CRC. Toxicity and disease-free survival (DFS) were analyzed retrospectively. RESULTS: The median dose intensities of oxaliplatin and 5-FU were 0.7 and 0.74, respectively. Oxaliplatin was discontinued in 10 (22%) patients due to an allergic reaction in five, neurotoxicity in four and gastrointestinal toxicity in one. No severe neurotoxicity occurred. The median duration from completion of treatment until complete recovery from peripheral neuropathy was 582 days (95% CI, 486-678). Two-year DFS for stages IIIb and IV was 56.9% and 56.3%, respectively (log-rank, P = 0.533). Univariate analysis revealed that severe vessel invasion, liver metastasis and higher baseline levels of CA19-9 were associated with shorter DFS in stage IV patients. Multivariate analysis including the selected biomarkers revealed none as a significant prognostic factor. CONCLUSION: Adjuvant FOLFOX was well tolerated in a Japanese cohort of both stage IIIb and IV CRC patients.