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. 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 preceding 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.