Pharmacokinetically guided dosing for intravenous melphalan: a pilot study in patients with advanced ovarian...

Pharmacokinetically guided administration of melphalan was investigated during a pilot study in patients with advanced ovarian adenocarcinoma. The schedule involved a fixed dose on day 1 (7.9 mg) followed by a second dose on day 2, calculated on the basis of pharmacokinetic data to achieve a target area under the concentration-time curve (AUC). 20 courses of intravenous melphalan were administered to 7 patients. AUC, standardised to 1 mg/m2, ranged between 4.3 and 8.9 (mg/l) min. In 12 fully evaluable courses, less than 15% deviation from the target AUC was found, showing that AUC monitoring was possible by means of the test dose. Pharmacodynamic effects showed a positive correlation with melphalan AUC. Myelosuppression appeared at 47 (mg/l) min and grade 3 or 4 haematological toxicities were observed in 4 cycles, associated with AUC values ranging between 86 and 112 (mg/l) min. Relative leucocyte decreases were well correlated with AUC values.