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Purpose: The current study aimed to determine the efficacy of trifluridine/tipiracil for elderly patients with advanced colorectal cancer. Methods: This single-arm, open-label, multicenter, phase II study included elderly patients aged 65 years or more who had fluoropyrimidine-refractory advanced colorectal cancer and received trifluridine/tipiracil (70 mg/m2, days 1–5 and 8–12, every 4 weeks). The primary endpoint was progression-free survival (PFS), while secondary endpoints included overall survival (OS), overall response rate (ORR), toxicities, association between efficacy and geriatric assessment scores, and association between toxicity and plasma drug concentrations. Results: A total of 30 patients with a mean age of 73 years were enrolled. Median PFS was 2.3 months (95% confidence interval, 1.9–4.3 months), while median OS was 5.7 months (95% confidence interval, 3.7–8.9 months). Patients had an ORR of 0%, with 57% having stable disease. Grade 4 neutropenia was observed in 13% of the patients. Patients with a higher G8 score (15 or more) showed longer PFS than those with a lower G8 score (median 4.6 vs. 2.0 months; p = 0.047). Moreover, patients with grade 3 or 4 neutropenia showed higher maximum trifluridine concentrations than those with grade 1 or 2 neutropenia (mean 2945 vs. 2107 ng/mL; p = 0.036). Discussion: The current phase II trial demonstrated that trifluridine/tipiracil was an effective and well-tolerated option for elderly patients with advanced colorectal cancer. Moreover, geriatric assessment tools and/or plasma drug concentration monitoring might be helpful in predicting the efficacy and toxicities in elderly patients receiving this drug. Trial registration number: UMIN000017589, 15/May/2015 (The University Hospital Medical Information Network) [ABSTRACT FROM AUTHOR]

Purpose: Although locally advanced head and neck squamous cell carcinoma (HNSCC) can be effectively treated using chemoradiotherapy (CRT) with docetaxel (DTX), and cisplatin (CDDP) plus 5-fluorouracil (TPF-CRT), severe adverse events (especially neutropenia) can limit treatment adherence. Therefore, we evaluated the safety and efficacy of a new chemotherapy regimen that consisted of DTX and CDDP plus cetuximab (Cmab) with concurrent radiotherapy. Methods: Bio-chemoradiotherapy (B-CRT) using DTX, CDDP, and Cmab was administrated to patients with locally advanced HNSCC, and its safety and efficacy were evaluated. Results: Interim analysis of nine patients revealed severe neutropenia in five patients (56 %) and leukopenia in seven patients (78 %); hence, the study was terminated. One patient experienced disease-free survival using only B-CRT. Conclusions: Neutropenia was equally severe for B-CRT, compared to TPF-CRT. Based on the limited sample size, it is impossible to conclude that B-CRT has non-inferior efficacy, compared to TPF-CRT. [ABSTRACT FROM AUTHOR]

Purpose: We conducted a phase I study for adjuvant chemotherapy of gemcitabine (GEM) plus S-1 in order to determine the maximum tolerated dose and the recommended dose (RD) and to evaluate the efficacy and toxicity of the regimen in curatively resected patients with biliary cancer. Methods: The study included 34 patients with adequate organ functions, Eastern Cooperative Oncology Group PS 0-1, under 80 years of age, who had curative resection after August, 2007. Patients received GEM on day 1 and day 15, and S-1 from day 1 to day 14. Dose-limiting toxicities were determined during first two treatment cycles. After determining RD, a feasibility study was continued in the following four treatment cycles. Results: Hematological toxicity, particularly neutropenia and thrombocytopenia, was the most pronounced toxic effect of gemcitabine and S-1 adjuvant combination chemotherapy. The RD after pancreatoduodenectomy is GEM 1,000 mg/m + S-1 80 mg/m, and RD after hemihepatectomy is GEM 800 mg/m + S-1 60 mg/m. Conclusions: The pharmacokinetics of GEM and S-1 indicate that changing the dose of adjuvant chemotherapy based on the operation method for biliary cancers is reasonable. We believe that this regimen will be established as an effective adjuvant chemotherapy for biliary cancer in the future. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate the feasibility and toxicity of concurrent chemoradiotherapy (CCRT) with docetaxel, cisplatin (CDDP) and 5-fluorouracil (5-FU) (TPF regimen) or with CDDP, 5-FU, methotrexate and leucovorin (PFML regimen) in previously untreated patients with advanced oropharyngeal squamous cell carcinoma (SCC). Methods: Fifty-six eligible patients with stage III or IV oropharyngeal SCC were treated with CCRT. Forty-four patients were men and 12 were women, and the average age of the patients was 58.8 years (range, 37-72 years). In the TPF group, patients received CCRT with the TPF regimen [docetaxel (50 mg/m, day 1), CDDP (60 mg/m, day 4) and a continuous 5-FU infusion (600 mg/m/day, days 1-5)]. In the PFML group, patients received CCRT with the PFML regimen [CDDP (60 mg/m, day 4), a continuous 5-FU infusion (600 mg/m/day, days 1-5), methotrexate (30 mg/m, day 1) and leucovorin (10 mg/m/day, days 1-5)]. The total radiation dose was between 66.6 and 70.2 Gy. Results: The overall 5-year survival rate was 64.6% in all patients, 68.6% in the resectable group and 47.4% in the unresectable group. The 5-year disease-specific survival rate was 72.2% in all patients, 78.1% in the resectable group and 47.7% in the unresectable group. Regarding clinical stage, the 5-year disease-specific survival rates were 91% in stage III, 72% in stage IVa and 44% in stage IVb. Conclusion: CCRT with TPF or PFML regimen for advanced oropharyngeal SCC is tolerable and effective, especially in patients with resectable disease. [ABSTRACT FROM AUTHOR]

We compared concurrent chemoradiotherapy (CCRT) with docetaxel, cisplatin (CDDP), and 5-fluorouracil (5-FU) (TPF) with CCRT with CDDP, 5-FU, methotrexate and leucovorin (PFML) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) in terms of safety and efficacy on survival. A total of 100 patients were enrolled. The TPF group received CCRT with the TPF regimen [docetaxel (50 mg/m2: day 1), CDDP (60 mg/m2: day 4), and continuous 5-FU infusion (600 mg/m2/day: days 1–5)]. In the PFML group, patients received CCRT with the PFML regimen [CDDP (60 mg/m2: day 4)], continuous 5-FU infusion (600 mg/m2/day: days 1–5), methotrexate (30 mg/m2: day 1) and leucovorin (20 mg/m2/day: days 1–5)]. Both groups received 2 cycles of chemotherapy during definitive radiotherapy. The total radiation dose was between 66.6 and 70.2 Gray. The overall response rates after CCRT were 98 with 90% of a pathologically complete response (pCR) in the TPF group and 94 with 77% in the PFML group. For grade 3/4 adverse events, mucositis was more frequent in the PMFL group, and the TPF group showed a higher incidence of hematological toxicity. CCRT with TPF or PMFL for advanced SCCHN was tolerable and produced excellent survival rates. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the feasibility and toxicity of concurrent chemoradiotherapy (CCRT) with S-1 in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) in elderly cases and/or cases with comorbidity. Fifty eligible patients with stage III (15 cases) or stage IV (35 cases) SCCHN were treated with CCRT. Thirteen cases had an advanced age of over 75 years and 37 cases had comorbidity. Definitive radiotherapy was delivered up to a total dose of 66–70.2 Gy. The patients received two courses of oral S-1 (40 or 50 mg twice a day [80 or 100 mg/day]) for 2 weeks followed by 1 week of rest while receiving CCRT. All the patients received the planned radiotherapy and at least one course of S-1. Grade 3 mucositis occurred in 20% of the patients (10/50). Grade 3 neutropenia occurred in 12% (6/50) and leukocytopenia occurred in 6% (3/50) of the cases. Pathologically, the complete response rates were 93% in stage III and 54% in stage IV. Concurrent chemoradiotherapy with S-1 is a safe, well-tolerated and effective regimen for locally advanced SCCHN in elderly cases and/or cases with comorbidity. [ABSTRACT FROM AUTHOR]