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Background: In East Asia, S-1 plus cisplatin (SP) is one of the standard first-line chemotherapy regimens for metastatic or recurrent gastric cancer (MRGC). Oxaliplatin is generally less toxic and more convenient to administer than cisplatin., Patients and Methods: This was a multicenter, phase III study assessing whether S-1/oxaliplatin (SOX) was non-inferior/superior to SP in terms of progression-free survival (PFS). Patients with MRGC were randomized 1:1 to receive either SOX (S-1 80 mg/m 2 /day on days 1-14; oxaliplatin 130 mg/m 2 on day 1; every 3 weeks) or SP (S-1 80 mg/m 2 /day on days 1-14; cisplatin 60 mg/m 2 on day 1; every 3 weeks [SP3])., Results: Between October 2012 and October 2014, 338 patients were randomized. The median age was 56 years, and 51% of patients had measurable lesions. SOX was significantly non-inferior but not superior to SP3 in terms of PFS [median 5.6 versus 5.7 months; hazard ratio (HR) 0.85; 95% confidence interval (CI) 0.67-1.07]. In patients with measurable disease, objective response rates were similar between SOX and SP3 (58% versus 60%). Overall, the survival in both groups did not differ (median 12.9 versus 11.4 months; HR 0.86; 95% CI 0.66-1.11). Treatment was well tolerated in both arms. Anemia, leucopenia, neutropenia, febrile neutropenia, and oral mucositis were more common with SP3. In contrast, thrombocytopenia, nausea, vomiting, and peripheral neuropathy were more common with SOX., Conclusions: SOX was non-inferior to SP3. The two regimens were well tolerated with different toxicity profiles. The SOX regimen can be recommended as a first-line treatment for MRGC., Trial Registration: ClinicalTrials.gov: NCT01671449.

Gemcitabine–oxaliplatin (GEMOX) demonstrated mild toxicity and promising effectiveness in patients with advanced urothelial cell cancer (UCC). We investigated the activity and safety of first-line GEMOX compared with gemcitabine–carboplatin (GCb) in cisplatin-ineligible patients with advanced UCC. Treatment-naive, cisplatin-ineligible patients with advanced UCC were randomly assigned to GEMOX (gemcitabine 1000 mg/m2, oxaliplatin 100 mg/m2 on day 1 [D1] every 2 weeks) or GCb (1000 mg/m2 of gemcitabine on D1 and D8 and carboplatin area under the curve of 4.5 mg/mL/min on D1 every 3 weeks). We evaluated the objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). Between January 2011 and March 2017, 80 patients were enrolled; 39 and 40 patients were allocated to GCb and GEMOX arms, respectively. The ORR was 48.7% in the GCb arm and 55.0% in the GEMOX arm. The median follow-up duration was 37.8 months; the median PFS and OS in the GCb and GEMOX arms were 5.5 months (95% confidence interval [CI], 4.8–6.2) vs. 4.4 months (95% CI, 2.7–6.1) and 9.1 months (95% CI, 5.2–13.0) vs. 11.0 months (95% CI, 6.9–15.0), respectively. ≥ Leucopenia, neutropenia and fatigue of ≥ grade III were significantly more common in the GCb arm (26% vs. 3%, P = 0.003; 33% vs. 10%, P = 0.014; 15% vs. 3%, P = 0.012), whereas any-grade neuropathy was more common in the GEMOX arm (8% vs. 60%). GEMOX showed similar efficacy with GCb and a favourable haematologic toxicity profile. GEMOX may be an additional chemotherapy option for patients with UCC ineligible for cisplatin-containing chemotherapy (NCT01487915). • Gemcitabine/carboplatin and gemcitabine/oxaliplatin had similar efficacy. • The toxicity profile differed between the two regimens. • Haematological toxicities and fatigue were more common in the gemcitabine/carboplatin arm. • Peripheral sensory neuropathy was more common in the gemcitabine/oxaliplatin arm. [ABSTRACT FROM AUTHOR]

Trastuzumab has been approved for use in combination with fluoropyrimidine plus cisplatin for the treatment of human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (AGC). Although capecitabine plus oxaliplatin (XELOX) is a standard first-line regimen for AGC, combination trastuzumab plus XELOX has not been studied. Patients with metastatic or unresectable HER2-positive AGC were diagnosed by either HER2 immunohistochemistry (IHC) 3+ or IHC 2+/fluorescence in-situ hybridisation (FISH)+ received intravenous trastuzumab (8 mg/kg for first cycle and 6 mg/kg for subsequent cycles on day 1) plus oral capecitabine (1000 mg/m2 twice daily on days 1–14) and intravenous oxaliplatin (130 mg/m2 on day 1), every 3 weeks. The primary end-point was the objective response rate, and secondary end-points included progression-free survival (PFS), overall survival (OS) and toxicity profiles. Fifty-five HER2-positive AGC patients were enrolled between August 2011 and February 2013. The median age was 57 years (range = 29–74). The confirmed objective response rate was 67% (95% confidence interval (CI) = 54–80%). After a median follow-up period of 13.8 months (range = 6.1–23.9), the median PFS and OS were 9.8 months (95% CI = 7.0–12.6) and 21.0 months (95% CI = 6.4–35.7), respectively. Frequently encountered grade 3–4 toxicities included neutropenia (18%), anaemia (11%), and peripheral neuropathy (11%). There was a treatment-related death caused by severe diarrhoea and complicated sepsis. Combination of trastuzumab and XELOX is well tolerated and highly effective in patients with HER2-positive AGC. [ABSTRACT FROM AUTHOR]

Summary: Background: Capecitabine plus oxaliplatin (CapeOX) is one of the reference doublet cytotoxic chemotherapy treatments for patients with metastatic colorectal cancer. We aimed to compare the efficacy and safety of CapeOX with that of S-1 plus oxaliplatin (SOX), a promising alternative treatment for patients with metastatic colorectal cancer. Methods: In this open-label, multicentre, randomised phase 3 trial, we randomly assigned patients (1:1) from 11 institutions in South Korea to receive either CapeOX (capecitabine 1000 mg/m2 twice daily on days 1–14 and oxaliplatin 130 mg/m2 on day 1) or SOX (S-1 40 mg/m2 twice daily on days 1–14 and oxaliplatin 130 mg/m2 on day 1). Treatment was repeated every 3 weeks and continued for as many as nine cycles of oxaliplatin-containing chemotherapy, except in instances of disease progression, unacceptable toxicity, or a patient''s refusal. Maintenance chemotherapy with S-1 or capecitabine was allowed after discontinuation of oxaliplatin. Randomisation was done with a computer-generated sequence (stratified by primary sites, previous adjuvant or neoadjuvant treatment, and the presence of measurable lesions). The primary endpoint was to show non-inferiority of SOX relative to CapeOX in terms of progression-free survival (PFS). The primary analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00677443. Findings: Between May 14, 2008, and Sept 23, 2009, we randomly assigned 168 patients to receive SOX and 172 to receive CapeOX. Median PFS was 8·5 months (95% CI 7·6–9·3) in the SOX group and 6·7 months (6·2–7·1) in the CapeOX group (hazard ratio, 0·79 [95% CI 0·60–1·04]; pnon-inferiority<0·0001, plog-rank=0·09). The upper limit of the CI was below the predefined margin of 1·43, showing the non-inferiority of SOX to CapeOX. We recorded a higher incidence of grade 3–4 neutropenia (49 [29%] vs 24 [15%]), thrombocytopenia (37 [22%] vs 11 [7%]), and diarrhoea (16 [10%] vs seven [4%]) in the SOX group than in the CapeOX group. The frequency of any grade of hand-foot syndrome was greater in the CapeOX group than it was in the SOX group (51 [31%] vs 23 [14%]). Interpretation: The SOX regimen could be an alternative first-line doublet chemotherapy strategy for patients with metastatic colorectal cancer. Further investigation is needed to explore its potential when used together with other targeted agents or as adjuvant chemotherapy. Funding: Korea Healthcare Technology Research and Development Project, Ministry of Health and Welfare, South Korea. [Copyright &y& Elsevier]

Abstract: Purpose: S-1 or capecitabine plus oxaliplatin are considered active and tolerable in gastric cancer patients. We conducted a randomized phase II trial in gastric cancer patients to compare the activity and safety of these combinations. Methods: The patients received S-1 at 80mg/m2 for 14days, followed by a 7-day rest period within a 3-week schedule in the S-1/oxaliplatin (SOX) arm, and capecitabine at 2000mg/m2 for 14days, followed by a 7-day rest period within a 3-week schedule in the capecitabine/oxaliplatin (CAPOX) arm. Oxaliplatin 130mg/m2 was administered every 3weeks in both arms. Results: One hundred twenty-nine patients were randomly assigned to SOX (N =65) or CAPOX (N =64). The median time to progression and the overall survival were 6.2 and 12.4months with SOX, respectively; and 7.2 and 13.3months with CAPOX, respectively. The overall response rates were 40% and 44% for SOX and CAPOX, respectively. The most frequent grade 3 or 4 toxicities were thrombocytopenia (15.4%) for SOX and neutropenia (18.8%) for CAPOX. The median time to 10% deteriorations in global health scores was similar in both arms (SOX, 4.3months, CAPOX, 4.9months). Conclusion: Both the SOX and CAPOX regimens were equally active and well tolerated in advanced gastric cancer patients. [Copyright &y& Elsevier]