Leukemia patients were recommended daily dose of 5 mg/m2day of semisynthetic homoharringtonine

10-17-2006

The recommended daily dose of subcutaneous (s.c.) semisynthetic homoharringtonine (SsHHT) on the 9-day schedule is 5 mg/m2day for patients with advanced acute myeloid leukemia.

According to researchers from France, "To determine the maximum-tolerated dose (MTD), dose-limiting toxicities and pharmacokinetic of ssHHT, given as a twice daily subcutaneous s.c. injections for 9 days, in patients with advanced acute leukaemia, 18 patients with advanced acute myeloid leukaemia were included in this sequential Bayesian phase 1 dose-finding trial. A starting dose of 0.5 mg/m2/day was explored with subsequent dose escalations of 1, 3, 5 and 6 mg/m2/day."

"Myelosuppression was constant," explained V. Levy and colleagues, Hopital St. Louis. "The MTD was estimated as the dose level of 5 mg/m2day for 9 consecutive days by s.c. route. Dose-limiting toxicities were hyperglycaemia with hyperosmolar coma at 3 mg/m2, and (i) 1 anasarque and haematemesis, (ii) 1 life-threatening pulmonary aspergillosis, (iii) 1 skin rash and (iv) 1 scalp pain at dose level of 5 mg/m2day.

"The mean half-life of ssHHT was 11.0+/-173.4 h, the volume of distribution at steady state was 2+/-1.41 kg-1 and the plasma clearance was 11.6+/-10.41 h-1. Eleven of the 12 patients with circulating leukaemic cells had blood blast clearance, 2 achieved complete remission and 1 with blast crisis of CMML returned in chronic phase."

The researchers concluded, "The recommended daily dose of ssHHT on the 9-day schedule is 5 mg/m2day."

Levy and colleagues published their study in British Journal of Cancer (A phase I dose-finding and pharmacokinetic study of subcutaneous semisynthetic homoharringtonine (SsHHT) in patients with advanced acute myeloid leukaemia. Br J Cancer, 2006;95(3):253-259).

For additional information, contact V. Levy, Hopital St. Louis, APHP, INSERM, CIC9504, Center Invest Clinic, 1 Avenue Claude Vellefaux, F-75475 Paris, France.

Publisher contact information for the British Journal of Cancer is: Nature Publishing Group, Macmillan Building, 4 Crinan St., London N1 9XW, England.

Keywords: Paris, France, Aspergillosis, Continual Reassessment Method, Homoharringtonine, Hyperglycemia, Leukemia, Oncology, Pharmacokinetic, Pharmacology, Phase I, Stopping Rules.

This article was prepared by Clinical Oncology Week editors from staff and other reports. Copyright 2006, Clinical Oncology Week via NewsRx.com.