Eight-hour infusion versus bolus injection of doxorubicin in the EAP regimen in patients with advanced gastric cancer: A prospective randomised trial

Background: Doxorubicin (40 mg/m(2)/cycle), etoposide (360 mg/m(2)/cycle) a nd cisplatin (80 mg/m(2)/cycle) comprise an efficient regimen in patients w ith advanced gastric cancer (AGC). However, its excessive hematological tox icity led doctors to avoid using the combination. Doxorubicin is the main c ause of myelotoxicity in the EAP regimen. The aim of this study was to comp are an eight-hour infusion of doxorubicin (arm A) with intravenous injectio n of doxorubicin (arm B) in the EAP regimen with respect to toxicity, objec tive responses, time to progression (TTP) and survival in patients with AGC . Patients and methods: One-hundred twenty chemotherapy-naive patients with m easurable AGC were randomised between September 1994 and August 1998. Sixty patients in arm A and sixty patients in arm B were considered as fully eva luable. The arms were well balanced for age, sex distribution, previous the rapy, histological grade and performance status. One-hundred eighty cycles were applied in arm A (median 2) and 201 in arm B (median 4). Results: No difference was detected (P = 0.28) in the response rate of arm A 20% (CR 3; PR 9; 95% CI: 10-30) and B 28% (CR 3; PR 14; 95% CI: 17-40). B ut there was a significant difference in PD (P = 0.005) between arm A (51%) and arm B (36%). TTP (P = 0.01) and survival (P = 0.02) analyses detected an advantage for arm B vs. arm A. Grades 3-4 toxicity were as follows (arms A%/B%): anemia 8/10, leukopenia 24/26, thrombocytopenia 6/16 (significance , P = 0.05), nausea/vomiting 5/8, diarrhea 6/2, mucositis 8/5. Apart from t he trombocytopenia, there was no significant difference in toxicity grades 3-4 between the two arms. Four treatment-related deaths occurred, two in ea ch arm. Conclusions: Bolus injection of doxorubicin is superior to eight-hour doxor ubicin infusion in the EAP regimen in terms of survival, TTP and PD without being significantly more toxic.