Dose Intensification of Etoposide in the BEAM ABMT Protocol for Malignant Lymphoma

We have previously demonstrated a dose response relationship in Hodgkin's disease for the combination of BCNU, VP16, Ara C and Melphalan, with the superior efficacy of the BEAM regimen requiring haemopoietic support, compared with miniBEAM.^1,2 To further exploit this, we have attempted to escalate the VP16 dose in BEAM. The standard etoposide dose is 200 mg/m² IV for four days. Thirty seven patients with refractory lymphoma received 400 mg/m²/day of etoposide, and 13 patients 600 mg/m²/day, in addition to BCNU, cytarabine, and melphalan. Toxicity and outcome parameters were compared in the preceeding 40 patients, who received 200 mg/m²/day etoposide. The toxic mortality with 400 mg/m²/day of etoposide (3%) was identical to that for the standard BEAM regimen (5%). Two procedure related deaths occurred in the highest VP16 dose group (15%). The morbidity of the lower etoposide dose regimens was comparable, but 600 mg/m²/day induced significantly greater gastrointestinal toxicity. Twelve of the 13 patients receiving this dose suffered grade II-IV mucositis, with stomatitis, dysphagia and prolonged diarrhoea; 5 haemodynamically significant gastrointestinal haemorrhage, and 1 fatal toxic colitis. Granulocyte colony stimulating factor did not influence the nonhaematological toxicity. The three month response rates were similar (91%) in all dose cohorts. The maximum tolerable etoposide dose within the BEAM regimen is thus 400 mg/m² for four days.