Unexpected Side Effects of a High S-1 Dose: Subanalysis of a Phase III Trial Comparing Gemcitabine, S-1 and Combinatorial Treatments for Advanced Pancreatic Cancer.
OBJECTIVE
In this subanalysis of a phase III trial using three categorized doses of S-1, the influence of the actual doses on safety and efficacy was evaluated.


METHODS
We compared the efficacy and safety of the S-1 or gemcitabine plus S-1 combination (GS) arm between the top 10% group and the bottom 10% group according to the initial doses of S-1: ≥77.6 versus ≤65.9 mg/m2/day (n = 28 vs. 28) in the S-1 arm, and ≥65.1 versus ≤53.8 mg/m2/day (n = 27 vs. 28) in the GS arm.


RESULTS
Overall and progression-free survival were not significantly different between these two groups: hazard ratios of 0.818 and 0.761 with p values of 0.498 and 0.330 in the S-1 arm, and hazard ratios of 0.836 and 0.759 with p values of 0.557 and 0.323 in the GS arm, respectively. Incidences of grade 3-4 hematological toxicities were significantly higher in the top 10% group than in the bottom 10% group: 42.9 versus 14.3 and 85.2 versus 57.1%, with p values of 0.037 and 0.037 in the S-1 and the GS combination arm, respectively.


CONCLUSIONS
Higher actual doses of S-1 were associated with a higher incidence of hematological toxicity even in the same dose setting.
Department of Gastroenterology, Hepatobiliary and Pancreatic Medical Oncology Division, Kanagawa Cancer Center, Yokohama City, Japan.
Satoshi
S
Kobayashi
Makoto
M
Ueno
Hiroki
H
Hara
Kuniyasu
K
Irie
Yoshihiro
Y
Goda
Satoshi
S
Moriya
Shun
S
Tezuka
Masao
M
Tanaka
Takuji
T
Okusaka
Shinichi
S
Ohkawa
Manabu
M
Morimoto
D000230:Adenocarcinoma / Q000188:drug therapy*; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D018196:Carcinoma, Adenosquamous / Q000188:drug therapy*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D004338:Drug Combinations; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects*; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D012189:Retrospective Studies; D015996:Survival Rate; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects*; D000093542:Gemcitabine
D004338:Drug Combinations; D003841:Deoxycytidine; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000093542:Gemcitabine