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

Abstract

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.

S-1 in combination with docetaxel and oxaliplatin in patients with advanced gastro-esophageal adenocarcinoma: two parallel phase 1/2a studies

“…Non-hematological toxicities were very infrequent at the RD levels (3A and 2B). The RD of S-1 is in line with the S-1 dose commonly recommended for Caucasian patients [5,23,24], but lower than doses used in East Asian patients; which we believe is due to more effective bioactivation of tegafur to 5-FU caused by higher activity of CYP2A6 in Caucasian patients [25].…”

Safe administration of S-1 after 5-fluorouracil-induced cardiotoxicity in a patient with colorectal cancer

“…For the time being, S-1 in Europe has been only approved for gastric cancer therapy. With respect to CRC, the experience with S-1 is limited to promising retrospective data in older Caucasian patients 4. However, prospective randomised survival data from a Dutch cohort are expected to be published soon 10.…”

Do we make progress in elderly patients with metastatic colorectal cancer?

“…A completed randomised Nordic study (Nordic 9), including 156 eligible Caucasian patients, revealed higher response rates, longer PFS, less severe toxicity with dose reduced combination chemotherapy (oxaliplatin and S1 compared with full dose monotherapy (S1) as 1st-line treatment in elderly (older than 70 years) patients not candidates for full dose combination chemotherapy [31]. S1 was prior to the Nordic 9 study favourably tested in a phase II study [32]. Further, S1 did in a Dutch randomised phase II study in Caucasian patients show similar activity to capecitabine, but with a significantly lower incidence of hand-foot syndrome [33].…”