Doxifluridine combined with weekly paclitaxel for second-line treatment in patients with gastric cancer resistant to TS-1.
BACKGROUND
Many patients with gastric cancer respond to TS-1, but some fail to respond or have recurrence. Second-line therapy is needed.


METHODS
We performed a pilot study in patients with advanced gastric cancer who did not respond to TS-1 or who had disease recurrence. The patients received oral doxifluridine (600 mg/day) on days 1 to 21 and an intravenous infusion of paclitaxel (70 mg/m(2)) on days 7, 14, and 21 of a 28-day cycle. The treatment was repeated until disease progression or prohibitive toxicity. Response rate, duration of response, median survival time (MST), effects on pleural effusion, ascites, and other signs, and toxicity were evaluated.


RESULTS
The study group comprised 52 patients. The response rate was 28%. The duration of response was 103 days. The MST after the start of second-line treatment was 175 days (95% confidence interval, 135 to 224 days). Pleural effusion or ascites resolved or decreased in 73% of the patients. Hair loss occurred in 32 patients (62%), and leukopenia developed in 28 (54%, grade 3 in 1 patient and grade 2 or lower in the others). The MST after the start of treatment with TS-1 was about 16 months.


CONCLUSIONS
A combination of doxifluridine and weekly paclitaxel is expected to be an effective second-line treatment for gastric cancer not responding to TS-1, especially in patients with malignant ascites or pleural effusion. However, it remains unclear whether paclitaxel plus doxifluridine results in a better response and survival benefit than paclitaxel alone in this subgroup of patients. Further studies are therefore necessary.
Arai
Wataru
W
Department of Surgery, Jichi Medical University, 3311-1 Shimotsuke, Tochigi 329-0498, Japan. waraitu@v005.vaio.ne.jp
Hosoya
Yoshinori
Y
Hyodo
Masanobu
M
Haruta
Hidenori
H
Kurashina
Kentaro
K
Saito
Shin
S
Hirashima
Yuuki
Y
Yokoyama
Taku
T
Zuiki
Toru
T
Sakuma
Kazuya
K
Yasuda
Yoshikazu
Y
Nagai
Hideo
H
D000008:Abdominal Neoplasms / Q000188:drug therapy / Q000556:secondary; D000310:Adrenal Gland Neoplasms / Q000188:drug therapy / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D005467:Floxuridine / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007564:Japan; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D010865:Pilot Projects; D017640:Silicates / Q000627:therapeutic use*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016019:Survival Analysis; D013997:Time Factors; D014025:Titanium / Q000627:therapeutic use*; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects
D017640:Silicates; D005467:Floxuridine; C103828:titanium silicide; D014025:Titanium; D017239:Paclitaxel; C025034:doxifluridine