Phase II study of UFT and oxaliplatin in first-line treatment of advanced colorectal cancer.
The purpose of this study was to evaluate the efficacy, assessed as response rate, and toxicity of UFT (Tegafur-Uracil) in combination with oxaliplatin as first-line treatment of advanced colorectal cancer (CRC). In all, 84 patients with recurrent or metastatic CRC with measurable disease were included. Treatment consisted of oxaliplatin 85 mg m(-2) in 120-min intravenous (i.v.) infusion on days 1 and 15; i.v. l,leucovorin (l,LV) 250 mg m(-2) given in 2 h on day 1, followed by oral UFT 390 mg m(-2) on days 1-14, and oral l,LV 7.5 mg/12 h on days 2-14. Cycles were repeated every 28 days. A total of 492 cycles of chemotherapy were delivered with a median of six per patient (range 1-12). There was one complete response (1%) and 28 partial responses (34%) for an overall response rate of 35% (95% confidence interval (CI): 24-46%). A total of 36 patients (44%) had stable disease, whereas 17 (21%) had a progression. The median time to progression was 7.3 months and the median overall survival was 16.8 months. A prescheduled preliminary analysis was performed after inclusion of 16 patients who detected a high gastrointestinal toxicity, which led to a reduction of the UFT dose to 300 mg m(-2). With this new dosage, grade 3-4 diarrhoea and grade 3-4 nausea/vomiting dropped to 21 and 14% of patients, respectively. Other grade 3-4 toxicities were stomatitis in one (1%), anaemia in three (5%), neutropenia in two (3%), thrombocytopenia in one(1%), fatigue in six (9%), peripheral sensory neuropathy in nine (14%) and laryngopharyngeal dysesthesia in two patients (2%). The combination of oxaliplatin and UFT-l,LV is an active, easy-to-administer regimen with moderate toxicity. Hence, this regimen is worthy of further investigation.
Feliu
J
J
Medical Oncology Service, Hospital La Paz de Madrid, Po de la Castellana, Madrid 261-28046, Spain. jfeliu.hulp@salud.madrid.org
Vicent
J M
JM
García-Girón
C
C
Constela
M
M
Fonseca
E
E
Aparicio
J
J
Lomas
M
M
Antón-Aparicio
L
L
Dorta
F J
FJ
Gonzalez-Baron
M
M
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D003967:Diarrhea / Q000139:chemically induced; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D000077150:Oxaliplatin; D013280:Stomatitis / Q000139:chemically induced; D016019:Survival Analysis; D005641:Tegafur / Q000008:administration & dosage* / Q000009:adverse effects; D014498:Uracil / Q000008:administration & dosage* / Q000009:adverse effects; D014839:Vomiting / Q000139:chemically induced
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D005641:Tegafur; D014498:Uracil