Multi-center phase II study for combination therapy with paclitaxel/doxifluridine to treat advanced/recurrent gastric cancer showing resistance to S-1 (OGSG 0302).
BACKGROUND
A pre-clinical study demonstrated that paclitaxel induced thymidine phosphorylase in the tumor tissues. The combination of paclitaxel and doxifluridine is expected to exert extra anti-tumor effects. We evaluated the efficacy of this combination in patients with unresectable or recurrent gastric cancer who had been previously treated with S-1.


METHODS
Registration was started to enroll 35 patients with advanced/recurrent gastric cancer, who were selected among those with measurable lesions fitting to response evaluation criteria in solid tumors, and with resistant to S-1 treatment. This regimen is consisted of paclitaxel, 80 mg/m(2), iv on days 1 and 8; and doxifluridine, 600 mg/m(2), po on days 1-14. The treatment was repeated every three weeks. Primary endpoint was response rate (RR); and secondary endpoints were overall survival (OS), progression free survival (PFS) and onset rate of adverse events.


RESULTS
From September 2003 to March 2005, 35 patients were registered: including 28 men; 7 women; median age of 66 years (range, 49-75 years); and performance status (PS) levels were, zero with 21 and one with 14 patients. In 33 eligible patients, except two, clinical usefulness was evaluated resulting in RR of 18.2% (partial response, 6; stable disease, 15; progressive disease, 10; and not evaluable, 2 patients). Median survival time was 321 days and median PFS was 119 days. Severe adverse events were found in three patients to discontinue the present treatment.


CONCLUSIONS
The combination of paclitaxel and doxifluridine might be a treatment of choice as a second line chemotherapy for patient undergone S-1 treatment.
Takiuchi
Hiroya
H
Cancer Chemotherapy Center, Osaka Medical College Hospital, 2-7 Daigakucho, Takatsuki, Osaka, 569-8686 Japan. in2028@poh.osaka-med.ac.jp
Goto
Masahiro
M
Imamura
Hiroshi
H
Furukawa
Hiroshi
H
Imano
Motohiro
M
Imamoto
Haruhiko
H
Kimura
Yutaka
Y
Ishida
Hideyuki
H
Fujitani
Kazumasa
K
Narahara
Hiroyuki
H
Shimokawa
Toshio
T
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D000368:Aged; D000740:Anemia / Q000139:chemically induced; D000855:Anorexia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004338:Drug Combinations; D019008:Drug Resistance, Neoplasm; D005260:Female; D005467:Floxuridine / Q000008:administration & dosage*; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary; D008175:Lung Neoplasms / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009503:Neutropenia / Q000139:chemically induced; D010094:Oxonic Acid / Q000494:pharmacology; D017239:Paclitaxel / Q000008:administration & dosage*; D010534:Peritoneal Neoplasms / Q000556:secondary; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000401:mortality; D015996:Survival Rate; D005641:Tegafur / Q000494:pharmacology; D013921:Thrombocytopenia / Q000139:chemically induced
D004338:Drug Combinations; D005467:Floxuridine; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D017239:Paclitaxel; C025034:doxifluridine