S-1 plus oxaliplatin on par with existing regimen for colorectal cancer treatment

Treatment with S-1, an oral fluoropyrimidine formulation similar to capecitabine, plus oxaliplatin (SOX) results in substantial improvements in overall response rate relative to capecitabine plus oxaliplatin (CapeOx) in patients with metastatic colorectal cancer, according to a Philippines study presented at the recent ESMO GI 2023.

“This suggests SOX as a possible first-line chemotherapy for metastatic colorectal cancer alternative to CapeOX,” said researchers J Lalusis and J Pandy from St Luke’s Medical Center, Quezon City, Philippines.

Lalusis and Pandy performed a systematic search of English-language articles on PubMed, Cochrane, and Google Scholar to identify randomized controlled trials (RCTs) that compared SOX with CapeOx in the treatment of metastatic colorectal cancer.

RCTs published from 2008 to February 2023 were included in the analysis. The Revised Cochrane risk-of-bias tool was used to assess the quality of studies. Finally, the researchers used inverse variance as the statistical method with random effects as the analysis model in the production of the Forest plot and calculation of risk ratio (RR) at 95 percent confidence intervals (CIs).

Four RCTs, including a total of 796 participants, met the eligibility criteria, all of which were carried out in Asia. Assessment of study quality revealed a low risk of bias. No heterogeneity was found (I², 0 percent; p=0.87), suggesting no significant between-group difference. [ESMO GI 2023, abstract P-220]

Notably, pooled results of the eligible RCTs showed a statistically significant improvement in overall response rate in patients treated with SOX regimen compared with those on CapeOx (RR, 1.41, 95 percent CI, 1.19‒1.66; p<0.0001).

S-1, also known as TS-1, consists of three components: tegafur, 5- chloro-2,4-dihydroxypyridine (gimeracil or CDHP), and oteracil potassium. Compared with capecitabine, S-1 demonstrates similar efficacy and a lower risk of hand-food syndrome.

“Several trials have shown the feasibility and efficacy of SOX as an upfront chemotherapy for metastatic colorectal cancer,” the researchers said. “There have also been several studies comparing SOX with CapeOx, a well-established first-line chemotherapy combination for metastatic colon cancer.”

Not inferior

In an earlier study conducted in China, SOX regimen for advanced or recurrent colorectal cancer treatment showed comparable efficacy with that of the combination of Xeloda and oxaliplatin (XelOx) and resulted in no additional toxicity. [J Cancer Res Ther 2015;11:331-335]

Specifically, the response rates were 54.3 percent with SOX and 42.9 percent with XelOX, while the disease control rates were 80.0 percent and 74.3 percent, respectively. The 1- and 2-year survival rates were 73.6 percent and 39.1 percent with SOX, respectively, compared with 73.8 percent and 37.8 percent with XelOx. Other parameters, including toxicity, did not differ significantly between the two treatment groups (p>0.05). [J Cancer Res Ther 2015;11:331-335]

“Therefore, S-1 could be used to substitute Xeloda in combined chemotherapy with oxaliplatin for the treatment of advanced or recurrent colorectal cancer,” the authors said.