FEP REGIMEN (EPIDOXORUBICIN, ETOPOSIDE AND CISPLATIN) IN ADVANCED GASTRIC-CANCER, WITH OR WITHOUT LOW-DOSE GM-CSF - AN ITALIAN TRIAL IN MEDICAL ONCOLOGY (ITMO) STUDY

The new regimens developed over the last few years have led to an impr ovement in the treatment of advanced gastric cancer, and our previous experience confirmed the fact that the combination of etoposide, doxor ubicin and cisplatin (EAP regimen) is an active treatment that leads t o interesting complete remission rates. The primary end point of the p resent multicentre, randomized, parallel-group phase II study was to d etermine the activity of the simplified 2-day EAP schedule in patients with locally advanced or metastatic gastric cancer, and to verify whe ther the addition of low doses of granulocyte-macrophage colony-stimul ating factor (GM-CSF) made it possible to increase dose intensity. Of the 62 enrolled patients, 30 were randomized to receive epirubicin 35 mg m(-2), etoposide 120 mg m(-2) and cisplatin 45 mg m(-2) (FEP) on da ys 1 and 2 every 28 days and 32 to receive the same schedule plus subc utaneous GM-CSF (molgramostin) 150 mu g day(-1) on days 5-14 every 21 days. The patients were stratified by age and the number of disease si tes. The characteristics of the patients were well balanced between th e two groups. The objective response rate of the patients as a whole w as 34% (21 out of 62; 95% confidence interval 22-46), with only one co mplete remission. The median response duration was 4.5 months (range 1 -24 months). The median time to treatment failure was 5 months (range 1-14 months), without any difference between the two groups. The media n survival of the patients as a whole was 9 months. Full doses were ad ministered in 92% and 94% of the cycles in the control and GM-CSF arms respectively. The average dose intensity calculated for all drugs was 0.96% in the control and 1.27% in the GM-CSF group. CTC-NCI grade 3-4 neutropenia was reported in 39% vs 45% of patients, thrombocytopenia in 11% vs 35% (P = 0.020) and anaemia in 7% vs 35% (P = 0.014). The FE P combination is as active (OR: 34%) in the treatment of patients with advanced gastric cancer as the EAP regimen, although it leads to fewe r complete remissions. The patients randomized to receive low-dose GM- CSF achieved a significantly higher dose intensity than controls (P = 0.0001).