Phase II feasibility study of high dose epirubicin plus etoposide and cisplatin (HDEEC) regimen in small cell lung cancer

Abstract

Seventeen patients with small cell lung cancer entered a phase II trial testing the feasibility of adding high dose epirubicin (100-120 mg/m2, day 1) in combination with etoposide (60-80 mg/m2, days 1-5) and cisplatin (70 mg/m2, day 1) courses repeated every three weeks. Complete responders received thoracic (40 Gy) and prophylactic cranial (30 Gy) irradiation. Sixteen patients were evaluable for response and toxicity. Myelosuppression was the dose-limiting side effect. Neutropenic fever was observed in eight patients (53%) and stomatitis in six (40%). No patient had a greater than 14% decline in the cardiac ejection fraction. Strict adherence to the dose-schedule designed was impossible as doses were trimmed and delayed in 30% of instances. The overall objective response rate was 81% (95% confidence limits, 62% to 100%), in limited disease there were complete remissions in 57%. With a 16 months median follow-up, overall median survival was 13 months. This study was unable to prove the feasibility of epirubicin escalation when added to etoposide-cisplatin combination, hampering the dose-intensification Norton-Simon model test.

Outpatient treatment with epirubicin and oral etoposide in patients with small-cell lung cancer

“…The overall median survival was 42 weeks, which is very similar to our own results. Higher doses of epirubicin (100-120 mg m-2) given on day 1 with cisplatin (70 mg m-2) and etoposide (60-80 mg m-2) for days 1-5 had a higher response rate at 81% and median survival of 13 months (Rosell et al, 1992). However, this was at the expense of increased toxicity with 53% neutropenic fever and 40% stomatitis compared with 15% grade 3 and 4 infection and 3% stomatitis in the ifosfamide-containing combination.…”

“…The combination of epirubicin and etoposide has been tested in several phase II trials but always in addition to other drugs, such as cyclophosphamide (Macchiarini et al, 1990b), cisplatin (Rosell et al, 1992), ifosfamide (Sculier et al, 1995) or in four drug regimens (Bamberga et al, 1992).…”