EORTC Early Clinical Studies Group early phase II trial of S-1 in patients with advanced or metastatic colorectal cancer

Abstract

Cancer of the colon and rectum is one of the most frequent malignancies both in the US and Europe. Standard palliative therapy is based on 5-fluorouracil/folinic acid combinations, with or without oxaliplatin or irinotecan, given intravenously. Oral medication has the advantage of greater patient convenience and acceptance and potential cost savings. S-1 is a new oral fluorinated pyrimidine derivative. In a nonrandomised phase II study, patients with advanced/metastatic colorectal cancer were treated with S-1 at 40 mg m À2 b.i.d. for 28 consecutive days, repeated every 5 weeks, but by amendment the dose was reduced to 35 mg m À2 during the study because of a higher than expected number of severe adverse drug reactions. In total 47 patients with colorectal cancer were included. In the 37 evaluable patients there were nine partial responses (24%), 17 stable diseases (46%) and 11 patients had progressive disease (30%). Diarrhoea occurred frequently and was often severe: in the 40 and 35 mg m À2 group, respectively, 38 and 35% of the patients experienced grade 3 -4 diarrhoea. The other toxicities were limited and manageable. S-1 is active in advanced colorectal cancer, but in order to establish a safer dose the drug should be subject to further investigations.

Phase I/II study of S-1 combined with cisplatin in patients with advanced gastric cancer

“…S-1 was approved in Japan for AGC under an accelerated approval regulation system in 1999, and for head and neck cancer in 2001, and clinical trials against colorectal (Ohtsu et al, 2000), breast (Sano et al, 2000), and lung cancer (Kawahara et al, 2001) are now ongoing and high responses have been reported. The phase II studies of S-1 against gastric (Chollet et al, 2003) and colorectal cancer (den Brande et al, 2003) in Europe by EORTC-Early Clinical Study Group also revealed high efficacy. Therefore, S-1 can be anticipated to be one of the key drugs for AGC.…”

Phase II study of oral S‐1 for treatment of metastatic colorectal carcinoma

“…Thus, the findings of the current study indicate that S-1 is a promising agent that has the potential to become a valuable oral treatment option, along with capecitabine and UFT ϩ LV, for patients with colorectal carcinoma. Clinical studies of S-1 in the treatment of metastatic colorectal and gastric malignancies 33,34 also suggest that S-1 possesses superior therapeutic activity compared with other regimens.…”

Dosage Escalation Study of S-1 and Irinotecan in Metronomic Chemotherapy against Advanced Colorectal Cancer

“…In phase II trials of S-1 as a single agent, response rates ranging from 19 to 39% were obtained in patients with advanced colorectal cancer [11][12][13]. These studies demonstrated that S-1 had a high response rate and good compliance in patients with advanced colorectal cancer treated on an outpatient basis.…”