The combinations of oral fluoropyrimidines and cisplatin such as capecitabine and cisplatin (XP) or S-1 and cisplatin (SP) are regarded as a standard therapy against unresectable, recurrent, or advanced gastric cancer (AGC). Especially, SP is the most common regimen against AGC in Japan. For patients with human epidermal growth factor receptor type 2 (HER2)-positive AGC, trastuzumab, a monoclonal antibody targeting HER2 antibody, is additionally used in combination. Although trastuzumab in combination with XP (trastuzumab-XP) have been widely accepted, the efficacy of trastuzumab in combination with SP (trastuzumab-SP) lacks sufficient verification. The aim of the present study is to validate the comparability of trastuzumab-SP to trastuzumab-XP. Patients with HER2-positive AGC were assigned to the trastuzumab-XP or trastuzumab-SP group. We then retrospectively compared the efficacy and safety between both groups. As a first-line chemotherapy, trastuzumab in combination with XP or SP was administered to 58 patients: 28 with trastuzumab-XP and 30 with trastuzumab-SP. In the trastuzumab-XP group, response rate (RR), disease control rate (DCR), median progression-free survival (mPFS), and median overall survival (mOS) were 39.3%, 89.3%, 7.9 months, and 20.0 months, respectively. In the trastuzumab-SP group, RR, DCR, mPFS and mOS were 50.0%, 86.7%, 6.9 months, and 16.7 months, respectively. No significant difference in efficacy was observed between both groups. Severe hand-foot syndrome was observed more frequently in the trastuzumab-XP group than in the trastuzumab-SP group (14.3% vs. 0%, p = 0.05). Trastuzumab in combination with SP is a potential first-line therapeutic option for patients with HER2-positive AGC.
Background Pseudomyxoma peritonei (PMP) is a rare malignancy, and there is insufficient evidence about systemic chemotherapy for this disease. Methods We retrospectively evaluated the efficacy and safety of a chemotherapeutic regimen with 5-fluorouracil and oxaliplatin (modified FOLFOX6, mFOLFOX6) for patients with unresectable pseudomyxoma peritonei. Patients who received the therapy between
Patients with BRAF‐mutated colorectal cancer (CRC) have a poor prognosis despite recent therapeutic advances such as combination therapy with BRAF, MEK, and epidermal growth factor receptor (EGFR) inhibitors. To identify microRNAs (miRNAs) that can improve the efficacy of BRAF inhibitor dabrafenib (DAB) and MEK inhibitor trametinib (TRA), we screened 240 miRNAs in BRAF‐mutated CRC cells and identified five candidate miRNAs. Overexpression of miR‐193a‐3p, one of the five screened miRNAs, in CRC cells inhibited cell proliferation by inducing apoptosis. Reverse‐phase protein array analysis revealed that proteins with altered phosphorylation induced by miR‐193a‐3p were involved in several oncogenic pathways including MAPK‐related pathways. Furthermore, overexpression of miR‐193a‐3p in BRAF‐mutated cells enhanced the efficacy of DAB and TRA through inhibiting reactivation of MAPK signaling and inducing inhibition of Mcl1. Inhibition of Mcl1 by siRNA or by Mcl1 inhibitor increased the antiproliferative effect of combination therapy with DAB, TRA, and anti‐EGFR antibody cetuximab. Collectively, our study demonstrated the possibility that miR‐193a‐3p acts as a tumor suppressor through regulating multiple proteins involved in oncogenesis and affects cellular sensitivity to MAPK‐related pathway inhibitors such as BRAF inhibitors, MEK inhibitors, and/or anti‐EGFR antibodies. Addition of miR‐193a‐3p and/or modulation of proteins involved in the miR‐193a‐3p–mediated pathway, such as Mcl1, to EGFR/BRAF/MEK inhibition may be a potential therapeutic strategy against BRAF‐mutated CRC.
Metastatic neuroendocrine tumors (gastrinomas) have a poor prognosis. Octreotide can reduce gastrin levels and alleviate hormonal symptoms, and possibly slow tumor growth as well. No drugs were available except streptozocin for the treatment of metastatic pancreatic neuroendocrine tumor (PNET) in 2008. We report a case of PNET in a 53-year-old woman with multiple liver tumors treated with S-1 plus octreotide. After 6 months from the initiation of the treatment, the pancreatic tumor and liver metastases regressed, and the patient achieved partial response without the development of any serious adverse event. For more than 8 years, the patient has remained asymptomatic without disease progression and is continuing treatment with octreotide and S-1. A marked suppression of gastrin levels has also been achieved. Combination therapy with octreotide and S-1 has been effective and well tolerated in patients with metastatic gastrinoma.
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