BackgroundThe mean 5–6-month survival after failed standard chemotherapy for metastatic colorectal cancer (mCRC) necessitates more effective treatments for refractory mCRC. For untreated mCRC, S-1 + oral leucovorin (SL) therapy offers promising results without severe toxicity. The ML18147 trial demonstrated that bevacizumab (Bev) prolongs overall survival after mCRC progression. We conducted a single-centre phase-II trial to evaluate the safety and efficacy of SL/Bev combination chemotherapy as mCRC salvage therapy.MethodsMajor eligibility criteria were confirmed adenocarcinoma diagnosis; age >20 years; Eastern Cooperative Oncology Group performance status, 0–2; and progression after administration/intolerance of/to approved drugs for mCRC. (5-FU, oxaliplatin, irinotecan, Bev, and anti-EGFR antibody, if KRAS wild-type). S-1 (80–120 mg/body) and leucovorin (25 mg) were orally administered in a 1-week-on/1-week-off schedule. Bev (5 mg/kg) was administered on day 1 of every 2-week cycle. The primary endpoint was disease control rate (DCR).ResultsA total of 31 patients were enrolled. DCR was 65 % [95 % confidence interval (CI), 48–100 %] and the response rate was 7 % (95 % CI, 0.7–22 %). One patient showing partial response to SL/Bev had a BRAF-mutant tumor. Median progression-free survival and overall survivals were 5.3 [95 % CI, 2.1–9.3] and 9.9 [95 % CI, 7.4–NA] months, respectively. The most-frequent grade-3/4 adverse events were mucositis (26 %) and diarrhea (11 %), which were manageable by dose reduction/interruption.ConclusionsSL/Bev showed impressive activity in refractory mCRC and was tolerable, suggesting its potential as an alternative chemotherapy for refractory mCRC.Trial registrationThis study has been registered in University Hospital Medical Information Network (UMIN) Clinical Trials Registry (IDUMIN000009083) on 11 October 2012.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1606-1) contains supplementary material, which is available to authorized users.

Our results suggest that baseline CA19-9 level is an independent prognostic factor in mCRC patients, and it correlated with the KRAS/BRAF mutation status. Bevacizumab exhibits clinical activity only for high CA19-9 levels in mCRC.

Three prognostic factors were identified in AGC patients treated with SP. Using a simple prognostic index, the patients were divided into three risk groups, in which the survival differences were markedly significant, suggesting that patients with good PS and only one metastatic site may have a higher chance of long-term survival than those with poor PS and multiple metastatic sites.

Here, we report a patient with gastric adenosquamous carcinoma (ASC) with human epidermal growth factor receptor-2 (HER2) overexpression who was successfully treated with trastuzumab-based chemotherapy. The patient was a 66-year-old man preoperatively diagnosed with gastric adenocarcinoma with no evidence of distant metastases. On histopathological examination, the curatively resected tumor was identified as ASC with mixed adenocarcinoma and squamous cell carcinoma components. Multiple liver metastases developed 2.5 months after surgery. Because immunohistochemical staining for HER2 was strong in both components, combination chemotherapy with capecitabine, cisplatin, and trastuzumab was initiated. A partial response was confirmed after 6 treatment cycles and PET and CT scans performed after 13 cycles revealed disease resolution with no uptake in the metastatic lesions. No evidence of disease progression has been observed 16 months after initial chemotherapy. This report suggests the potential utility of trastuzumab-based chemotherapy for HER2-positive gastric ASC.

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