Efficacy of S-1 in heavily pretreated patients with metastatic breast cancer: cross-resistance to capecitabine.
BACKGROUND
It is not clear what the optimal treatment of chemotherapy is for patients with heavily treated metastatic breast cancer (MBC). We have retrospectively examined the efficacy and safety of S-1 in patients with MBC who had been previously treated with anthracycline, taxane, and capecitabine.


METHODS
Patients with MBC who had been administered S-1, an oral modulated compound containing a fluoropyrimidine derivative, between November 2001 and June 2003 at the Cancer Institute Hospital were retrospectively reviewed. S-1 at a standard dose of 50 mg/body was administered twice daily for four weeks, followed by a two-week rest period. This was repeated every six weeks until disease progression or unacceptable toxicity.


RESULTS
Thirty-five patients were assessed. The patients were heavily pretreated with anthracycline (100%), taxane (paclitaxel or docetaxel) (100%), capecitabine (100%), vinorelbine (71%), and mitomycin (69%). Median follow-up time of patients was 9.6 months (range, 1.2-26.6). ORR was 3% (95% confidence interval: 0-9%), and CBR was 20% (95% confidence interval: 6-33%). Time to treatment failure was 2.8 months. Overall survival was 21.4 months. Grade 1 or 2 adverse events were observed in 17% and 13%, respectively. Grade 3 events occurred as anorexia (9%), nausea (9%), vomiting (9%), diarrhea (14%), fatigue (3%), and elevation of AST/ALT (3%). No grade 3 was seen as hand-foot syndrome. Neither grade 3 nor 4 was observed in bone marrow suppression.


CONCLUSIONS
S-1 was fairly well tolerated, but demonstrated very limited activity in capecitabine-pretreated patients who had already been exposed to anthracycline and taxane. It was suggested that S-1 clinically exhibited cross-resistance to capecitabine.
Ito
Yoshinori
Y
Department of Medical Oncology, The Cancer Institute of Japanese Foundation for Cancer Research, 3-10-6, Ariake, Koto-ku, Tokyo, 135-8550, Japan. yito@jfcr.or.jp
Osaki
Yohei
Y
Tokudome
Nahomi
N
Sugihara
Tsutomu
T
Takahashi
Shunji
S
Iwase
Takuji
T
Hatake
Kiyohiko
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018943:Anthracyclines / Q000008:administration & dosage; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D001952:Bridged-Ring Compounds / Q000008:administration & dosage; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004338:Drug Combinations; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000188:drug therapy; D009367:Neoplasm Staging; D010094:Oxonic Acid / Q000627:therapeutic use*; D010997:Pleural Neoplasms / Q000188:drug therapy* / Q000556:secondary; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D005641:Tegafur / Q000627:therapeutic use*; D016896:Treatment Outcome
D018943:Anthracyclines; D000964:Antimetabolites, Antineoplastic; D001952:Bridged-Ring Compounds; D004338:Drug Combinations; D043823:Taxoids; D003841:Deoxycytidine; C079198:S 1 (combination); D005641:Tegafur; C080625:taxane; D010094:Oxonic Acid; D000069287:Capecitabine; D005472:Fluorouracil