A Randomized Phase II Dose-Finding
Trial of Thalidomide and Prednisone as Maintenance Therapy For Myeloma
Following Autologous Stem Cell Transplant: NCIC Clinical Trials Group, Queen's University, Kingston, ON, Canada.
AK Stewart, C. Chen, K. Howson-Jan, D. White, J. Roy, M. Kovacs, C.
Shustik, A. Sadura, L. Shepherd, K. Ding, RM. Meyer, A. Belch
Purpose: To define the appropriate dose of thalidomide
when combined with alternate day prednisone as maintenance therapy following
autologous stem cell transplantation (ASCT) in multiple myeloma (MM) patients.
Methodology:
Consenting patients undergoing ASCT within 1 year of initial therapy were
eligible for this multi-centre open – label randomized phase II study.
Sixty – 100 days following ASCT, patients were randomized to receive thalidomide
200 mg or 400 mg daily. All patients received prednisone 50 mg on alternate
days. A dose attenuation schedule was utilized for both drugs. The primary
endpoint was the need to dose - reduce or discontinue thalidomide during
the initial six months of therapy. Early stopping rules were implemented
if the primary endpoint was met in 7 of the first 20 patients in either
arm. Results: Between July 2000 and Sept. 2001, 67 patients were
enrolled. Median follow up is 6 months. Twenty-two patients were accrued
to the 400mg arm which was closed early because of intolerability in 12
of the first 20 patients. Median duration of follow-up in the 400 mg arm
was 9 months. The thalidomide 200 mg arm accrued 45 patients (median follow
up 4.1 months). Seven of 16 (44%) patients on thalidomide 200 mg and followed
>6 months have also dose reduced or stopped drug. Dose – limiting toxicities
(> grade 2) include neuropathy 15.9%, constipation 26.9%, dizziness
9.5%, sedation 11.1%, mouth dryness 4.3%, skin rash 12.7%. Infection occurred
in 32% of patients and venous thrombosis has been observed in 7.5% of patients
to date. Summary: When combined with prednisone 50mg on alternate
days, 60% of MM patients post ASCT are unable to tolerate thalidomide maintenance
of 400 mg per day. A substantial number of patients treated with thalidomide
200 mg per day also experience dose-limiting toxicity. A final analysis
will be conducted in April 2002, when all patients have completed 6 months
of therapy. These results have important implications in the design of
phase III trials testing this treatment strategy.
