S-1 plus oxaliplatin versus capecitabine plus oxaliplatin for first-line treatment of patients with metastatic colorectal cancer: a randomised, non-inferiority phase 3 trial

Hong, Yong Sang; Park, Young Suk; Lim, Ho Yeong; Lee, Jeeyun; Kim, Tae Won; Kim, Kyu Pyo; Kim, Sun Young; Baek, Ji Yeon; Kim, Jee Hyun; Lee, Moon Hyoung; Chung, Ik Joo; Cho, Sang‐Hee; Lee, Kyung Hee; Shin, Sang Joon; Kang, Hye Jin; Shin, Dong Bok; Jo, Sook Jung; Lee, Jae Won

doi:10.1016/s1470-2045(12)70363-7

Cited by 119 publications

(119 citation statements)

References 31 publications

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“…Randomized studies in Japanese patients have shown that S-1 is as effective as other fluoropyrimidines (5-FU and capecitabine) when given either as monotherapy or in combination with oxaliplatin [11,12] or irinotecan [13]. In the phase 3 'SOFT' study chemo-na€ ıve patients were randomized to mFOLFOX6 plus bevacizumab or SOx plus bevacizumab [12].…”

Section: Discussionmentioning

confidence: 99%

Experience with S-1 in older Caucasian patients with metastatic colorectal cancer (mCRC): Findings from an observational chart review

et al. 2016

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Background: An aging population will increase the number of older patients with metastatic colorectal cancer (mCRC). However, there is limited knowledge about treatment in older patients as they are under-represented in clinical trials. The oral fluoropyrimidine S-1 is associated with a lower rate of adverse events than capecitabine and may therefore be a suitable drug for elderly. However, data on the use of S-1 in Caucasian mCRC patients are lacking/scarce. Material and methods: In the present study we evaluated safety and the efficacy of S-1 alone or in combination with oxaliplatin (SOx) or irinotecan (IRIS) in older mCRC patients. Patients who received at least one cycle of S-1 (first-line therapy), SOx (mainly first-line therapy) or IRIS (second-line therapy) were included. Results: From June 2012 to December 2014, 71 older patients received 1 cycle of either S-1 (n ¼ 9), SOx (n ¼ 44) or IRIS (n ¼ 18) for mCRC. Median age was 76 years and most patients had a WHO performance status of 0 (32%) or 1 (56%). All patients were evaluable for response and safety. In the SOx group, 18 (41%) and 20 patients (45%) had partial response (PR) and stable disease (SD), respectively (disease control rate 86%). Median progression-free survival (PFS) was 8.5 months and median overall survival (OS) was 18.5 months. In the S-1 group (median age 82 years), PR was 22%, median PFS 6.4 months and median OS 15.8 months. In the IRIS group, PR was 28%, median PFS 7.8 months and the median OS 16.5 months. In general, therapy was well tolerated; main non-hematological toxicities were fatigue and diarrhea. Conclusion: S-1 monotherapy, SOx and IRIS were well tolerated for older patients with mCRC and could become alternative regimens in older mCRC patients. These regimens are now further evaluated in the randomized ongoing NORDIC9 trial.

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Section: Discussionmentioning

confidence: 99%

Experience with S-1 in older Caucasian patients with metastatic colorectal cancer (mCRC): Findings from an observational chart review

et al. 2016

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“…Therefore, a potential advantage of the use of S-1 in oxaliplatin schedules (SOX) over CAPOX is a reduced frequency of HFS. Hong et al [65] conducted a noninferiority phase 3 trial comparing SOX and CAPOX as first-line treatment of mCRC in Asian patients. Non-inferiority was confirmed in terms of median PFS (8.5 vs. 6.7 months, respectively, hazard ratio (HR) 0.79, p non-inferiority < 0.0001).…”

Section: Sox Versus Capoxmentioning

confidence: 99%

Oral drugs in the treatment of metastatic colorectal cancer

Kwakman

Punt

2016

Expert Opinion on Pharmacotherapy

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Introduction: Intravenous administration of fluoropyrimidine-based chemotherapy has been the cornerstone of treatment in metastatic colorectal cancer (mCRC) for decades. The availability of oral capecitabine has improved the tolerability in monotherapy schedules, and has simplified combination schedules. Since then, other oral drugs have proven efficacy in this setting. Areas covered: We review the available evidence and most recent data concerning oral drugs with proven efficacy in mCRC, including capecitabine, S-1, trifluridine-tipiracil (TAS-102) and regorafenib. Expert opinion: The use of capecitabine is widely implemented in the care of mCRC. However, with recent data supporting its prolonged use, the relatively high incidence of hand-foot syndrome (HFS) may impair quality of life. In Asian populations, S-1 is associated with equivalent efficacy but lower incidence of HFS compared to capecitabine. Further studies evaluating the effects of S-1 in Western populations are needed. Both regorafenib and TAS-102 improve the overall survival of patients in whom all other treatment options have failed. Since only a subset of patients appears to benefit, future studies to identify predictive biomarkers are needed. ARTICLE HISTORY

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“…In phase II studies, S-1 alone elicited an RR of 19-40% with tolerable adverse events in patients with metastatic colorectal cancer (15)(16)(17). Furthermore, several trials using SOX regimens have reported RRs of 47-54% and DCRs of 81-90% (6,18,19). In those studies, the median PFS of patients receiving SOX regimens was 6.5-8.5 months, while the median OS was 21.2-27.2 months, highlighting the efficacy and feasibility of SOX as first-line chemotherapy for metastatic colorectal cancer (6,18,19).…”

Section: Discussionmentioning

confidence: 99%

“…S-1 is an oral anticancer drug that combines the prodrug tegafur with two modulators of 5-FU metabolism, gimeracil and oteracil (4). Several phase III clinical trials on metastatic colorectal cancer have demonstrated that oral S-1 may substitute infusional 5-FU (5,6). Furthermore, a phase III trial of first-line treatments in patients with metastatic colorectal cancer (SOFT trial) demonstrated that the combination of S-1 and oxaliplatin with bevacizumab (SOX+bev) was as efficacious as FOLFOX6+bev with respect to progression-free survival (PFS) (7).…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of oxaliplatin, bevacizumab and oral S-1 for advanced recurrent colorectal cancer

Suzuki

Shimazaki

Morishita

et al. 2016

Molecular and Clinical Oncology

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Abstract. The aim of this study was to evaluate the efficacy and safety of co-administration of oral S-1 and oxaliplatin (SOX) in combination with bevacizumab (bev) in patients with advanced recurrent colorectal cancer. A retrospective study of 36 patients with advanced recurrent colorectal cancer was performed, of whom 27 received first-line and 9 received second-line SOX+bev chemotherapy between 2010 and 2013 at the Hachioji Digestive Disease Hospital (Hachioji, Japan). The SOX+bev regimen consisted of administration of intravenous oxaliplatin (85 mg/m 2 ) on days 1 and 14, bevacizumab (5 mg/kg) on day 1, and co-administration of oral S-1 twice daily on days 1-14. The drug regimen was repeated every 4 weeks. SOX+bev treatment was associated with a response rate of 45.2%, a disease control rate of 71%, and a median progression-free survival (PFS) and overall survival (OS) of 9.9 and 21.9 months, respectively. Patients who received first-line chemotherapy benefited from treatment in terms of prolonged PFS (13.8 months) and OS (28.2 months). Grade 3/4 adverse events were infrequent and included anaemia, thrombocytopenia, anorexia, diarrhea, sensory neuropathy, increased aspartate aminotransferase level and skin rash. In conclusion, SOX+bev therapy was found to be feasible and safe for patients with advanced and recurrent colorectal cancer. IntroductionThe combination of leucovorin, 5-fluorouracil (5-FU), and oxaliplatin (FOLFOX) and bevacizumab (bev) has been extensively used as first-line treatment for metastatic colorectal cancer (1,2). However, infusion or injection of 5-FU with leucovorin has certain disadvantages, including increased cost, inconvenience and morbidity associated with the use of a portable infusion pump and central venous catheter (3). The use of oral anticancer drugs has helped to overcome problems associated with continuous infusion, infection and thrombosis. S-1 is an oral anticancer drug that combines the prodrug tegafur with two modulators of 5-FU metabolism, gimeracil and oteracil (4). Several phase III clinical trials on metastatic colorectal cancer have demonstrated that oral S-1 may substitute infusional 5-FU (5,6). Furthermore, a phase III trial of first-line treatments in patients with metastatic colorectal cancer (SOFT trial) demonstrated that the combination of S-1 and oxaliplatin with bevacizumab (SOX+bev) was as efficacious as FOLFOX6+bev with respect to progression-free survival (PFS) (7). Therefore, the aim of the present study was to evaluate the efficacy and safety of SOX+bev for patients with advanced recurrent colorectal cancer. Patients and methods Patients.A total of 36 patients with advanced recurrent colorectal cancer who were administered SOX+bev chemotherapy between January, 2010 and December, 2013 at the Department of Surgery, Hachioji Digestive Disease Hospital (Tokyo, Japan) were included in this retrospective study. All patients provided written informed consent prior to treatment initiation. All the patients had sufficient oral drug intake. The patient inclusion...

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S-1 plus oxaliplatin versus capecitabine plus oxaliplatin for first-line treatment of patients with metastatic colorectal cancer: a randomised, non-inferiority phase 3 trial

Cited by 119 publications

References 31 publications

Experience with S-1 in older Caucasian patients with metastatic colorectal cancer (mCRC): Findings from an observational chart review

Experience with S-1 in older Caucasian patients with metastatic colorectal cancer (mCRC): Findings from an observational chart review

Oral drugs in the treatment of metastatic colorectal cancer

Efficacy and safety of oxaliplatin, bevacizumab and oral S-1 for advanced recurrent colorectal cancer

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