Safety, compliance, and predictive parameters for dosage modification in adjuvant S-1 chemotherapy for gastric cancer.
This study was performed to investigate the compliance, safety, dosage modifications (dose reduction and/or schedule change [including permanent S-1 withdrawal]), and clinical parameters that predict S-1 dosage modification in gastric cancer patients receiving adjuvant S-1 chemotherapy. One hundred and forty-nine patients who underwent curative D2 surgery and received adjuvant S-1 chemotherapy were enrolled. S-1 was administered orally (40 mg/m(2) twice daily on days 1-28 every 6 weeks) for 1 year. For patients unable to tolerate S-1, the dosage was reduced or the schedule was changed to a 3-weekly schedule of 2 weeks on treatment followed by 1 week off treatment. The planned 1-year treatment was completed in 73.8% of patients; 69 patients required dosage modification because of toxicity. The most frequent cause of dosage modification was enterocolitis (37 patients; defined as ≥ grade 2 abdominal pain and/or ≥ grade 2 diarrhea). Most dosage modification occurred during the early cycles of treatment (within the first 3 months). Severe toxicities (≥ grade 3) included neutropenia (13.4%), abdominal pain (8.1%) and diarrhea (8.1%). In multivariate analyses, decreased relative dose intensity was related to poor disease-free survival independent of stage, and only low creatinine clearance predicted S-1 dosage modification. In conclusion, although adjuvant S-1 therapy has a high compliance rate, meticulous monitoring of adverse events is required in the early period of treatment. Decreased creatinine clearance was the only factor that predicted dosage modification. In patients with creatinine clearance <50 mL/min, dosage reduction should be considered from the initiation of S-1 treatment.
Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
Su-Jung
SJ
Kim
Yu Jung
YJ
Kim
Jee Hyun
JH
Kim
Do Joong
DJ
Park
Hyung-Ho
HH
Kim
Jong Seok
JS
Lee
Keun-Wook
KW
Lee
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D015331:Cohort Studies; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010349:Patient Compliance; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000601:surgery; D015996:Survival Rate; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid