Treatment of patients with advanced gastric carcinoma with the combination of etoposide plus oral tegafur modulated by uracil and leucovorin. A phase II study of the ONCOPAZ Cooperative Group.
BACKGROUND
Both the biochemical modulation and the continuous administration of 5-fluorouracil (5-FU) have achieved promising results in patients with gastric carcinoma. Conversely, several studies on gastric carcinoma have demonstrated that the combination of etoposide (VP-16), leucovorin (LV), and 5-FU (ELF) is efficacious and moderately toxic. UFT is a combination of uracil and tegafur (ftorafur) in a 4:1 molar ratio. It can be administered orally for several weeks, thus stimulating the effects of a continuous infusion of 5-FU. Its combination with LV increased the efficacy of UFT. We conducted a Phase II study on patients with gastric carcinoma using the combination VP-16-LV-UFT. This combination is administered mainly orally (p.o) and could yield a good response rate and low toxicity.


METHODS
Forty-six patients with bidimensionally measurable disease were entered into the study. Patients received VP-16 100 mg/m2 IV on Day 1 and 200 mg/ m2 p.o. on Days 2 and 3; LV 500 mg/m2 administered intravenously (i.v.) on Day 1, followed by p.o. LV 15 mg every twelve hours on Days 2 to 14. Patients also received UFT p.o. 390 mg/m2/day on Days 1 to 14. Treatment was repeated every 28 days for a minimum of 3 courses per patient. All courses were given on an outpatient basis.


RESULTS
Four patients (9%) had a complete response, and 12 a partial response (26%) for an overall response rate of 35% (95% confidence interval: 22-51%). The median duration of response was 10 months. The median overall survival was 9 months. The main side effects were gastrointestinal. Grade 3 to 4 toxicity was encountered as follows: diarrhea in 17% of the patients, nausea/vomiting in 11%, anemia in 13%, mucositis and leukopenia in 4% each, and thrombocytopenia in 2%. One patient died of sepsis and neutropenia.


CONCLUSIONS
VP-16-LV-UFT has an activity comparable to that of other schemes and a low incidence of side effects. Furthermore, since it is administered mainly orally, hospitalization is avoided, which makes this scheme suitable for patients with advanced gastric carcinoma.
Feliu
J
J
Hospital La Paz, Paseo de la Castellana, Madrid, Spain.
González Barón
M
M
García-Girón
C
C
Espinosa
E
E
García-Alfonso
P
P
Belón
J
J
Blanco
E
E
Garrido
P
P
Ordónez
A
A
Gómez-Navarro
J
J
Zamora
P
P
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000553:Ambulatory Care; D000740:Anemia / Q000139:chemically induced; D000931:Antidotes / Q000008:administration & dosage*; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy*; D003967:Diarrhea / Q000139:chemically induced; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage* / Q000009:adverse effects; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007275:Injections, Intravenous; D002955:Leucovorin / Q000008:administration & dosage*; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D012074:Remission Induction; D013274:Stomach Neoplasms / Q000188:drug therapy*; D015996:Survival Rate; D005641:Tegafur / Q000008:administration & dosage* / Q000009:adverse effects; D014839:Vomiting / Q000139:chemically induced
D000931:Antidotes; D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D005641:Tegafur; D005047:Etoposide; D002955:Leucovorin; D005472:Fluorouracil