A phase II study of S-1 in patients with metastatic breast cancer--a Japanese trial by the S-1 Cooperative Study Group, Breast Cancer Working Group.
BACKGROUND
S-1 is a newly developed novel oral dihydrouracil dehydrogenase inhibiting fluoropyrimidine drug consisting of 1 M tegafur (FT), 0.4 M 5-chloro-2, 4-dihydroxypyrimidine (gimeracil), and 1 M potassium oxonate (oteracil), with efficient antitumor activity and low gastrointestinal toxicity which is widely used in Japan against advanced gastric, head and neck cancers. We investigated its clinical efficacy against metastatic breast cancer.


METHODS
A non-blind phase II study was carried out to evaluate the efficacy and toxicity in metastatic breast cancer patients. Patients with measurable metastasis foci (n=111) were enrolled, and 108 patients were regarded as eligible. S-1 was administered orally at a standard dose of 80 mg/m2/day b.i.d. One course consisted of 28 consecutive days of administration followed by a 14-day rest, and courses were repeated up to six times.


RESULTS
Among the eligible patients, 10 had a complete response and 35 had a partial response, with an overall response rate (CR+PR) of 41.7% (95% confidence interval: CI, 32.3-51.5%). The incidences of toxicity (> or =grade 3) were neutropenia 9.1%, anemia 0.9%, anorexia 3.6%, stomatitis 1.8%, nausea/vomiting 1.8%, diarrhea 0.9%, and fatigue 2.7%, however no treatment-related deaths were observed. The median survival time was 872 days (95% CI, 572-1,110 days). There was no difference in response rate or toxicity between the under 65-year-old group and the older group.


CONCLUSIONS
S-1 was demonstrated to have high efficacy with low gastrointestinal toxicity even in older patients and will be a promising new chemotherapy drug for metastatic breast cancer.
Saek
Toshiaki
T
Department of Clinical Research and Surgery, National Shikoku Cancer Center Hospital, Horinouchi 13, Matsuyama 790-0007, Japan. tsaeki@shikoku-cc.go.jp
Takashima
Shigemitsu
S
Sano
Muneaki
M
Horikoshi
Noboru
N
Miura
Shigeto
S
Shimizu
Satoru
S
Morimoto
Ken
K
Kimura
Morihiko
M
Aoyama
Hideaki
H
Ota
Jun
J
Noguchi
Shinzaburo
S
Taguchi
Tetsuo
T
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010094:Oxonic Acid / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D011725:Pyridines / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D005641:Tegafur / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D011725:Pyridines; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid