Epidoxorubicin and Double Biochemical 5-Fluorouracil Modulation with Folinic Acid and Human Lymphoblastoid Interferon in Advanced Gastric Carcinoma: A Multicentric Phase II Study of the Southern Italy Oncology Group (GOIM)

Abstract

In our previous randomized trial of advanced gastric cancer patients, the addition of epirubicin (EPI) to 5-fluorouracil (FU) with folinic acid (FA) resulted in an improved response rate and survival in the responder patients. Preclinical studies also showed an enhancement of FU and anthracyclines with interferon. To evaluate the possibility of human lymphoblastoid interferon (IFN) to enhance the therapeutic activity of the FA-FU + EPI combination regimen, 39 advanced gastric cancer patients received: FU at 375 mg/m² i.v. immediately after FA (l-isomer form) at 100 mg/m² i.v. for 5 consecutive days; EPI at 60 mg/m² i.v. on day 1, and IFN 3 MU s.c. for 7 consecutive days, starting 2 days before the FA-FU administration. Thirty-seven patients were evaluable for response and toxicity. Twelve partial responses were observed with an overall response rate of 32% (95% CI, 17–48%). The median response duration was 6 months, and the median survival time was 8 months. Toxicity was mild and no grade 4 side effects or treatment-related deaths were observed. However, the addition of IFN to the FA-FU + EPI regimen did not improve response, duration of response or survival.

Treatment of patients with advanced gastric carcinoma with a 5-fluorouracil-based or a cisplatin-based regimen

“…It achieves a 21% response rate in collected studies28; a higher response rate, although still unconfirmed, also has been reported in small Phase II studies using continuous infusion of 5‐FU or LV biomodulation, although the best schedule of such modulation has not yet been defined 7‐9, 29. More complex modulations of 5‐FU, involving interferon, do not add any advantages to LV modulation 30. 5‐FU also is a common component in many widely used regimens of combination chemotherapy.…”

“…Combination chemotherapy, with or without 5‐FU, often has shown response rates of ≥ 30%, but also has generally produced greater toxic effects. In spite of this, median patient survival remains between 8‐12 months 4, 10‐16, 30‐37. Moreover, the same drug combination frequently showed a lower response rate in confirmatory Phase II or in Phase III studies.…”