Haematologica 2003 - Supplements

325
Low Dose Thalidomide plus Dexamethasone Schedules
Produce Equivalent Results with Less Toxicity than
Higher Doses in both Frontline and Relapse Myeloma
Brian G.M. Durie, Eli Gabayan, Daniel E. Stepan
Cedars-Sinai Comprehensive Cancer Center, Los Angeles, CA
90048
Starting in October 1998, low dose thalidomide (50-100mg q.d.
H.S.) was used for myeloma treatment with evaluation of
response, time to progression, tolerance and overall survival. 83
patients are available for analysis. 36 relapse patients initially
received low dose thalidomide alone, then had dexamethasone
added; 47 patients received low dose thalidomide/
dexamethasone: 21 as frontline and 26 at relapse. In the first 36
patients starting with thalidomide alone, there was dose
escalation of thalidomide (50, 100, 150, 200). In the subsequent
patients and in the dexamethasone combinations, the dosage was
50 or 100mg.
Eleven of 36 patients started on thalidomide monotherapy had
dexamethasone added. 6/11 (55%) responded (> 50% regression)
with added dexamethasone. 13/21 frontline patients (62%)
responded: 2 patients had < 50% regression; 3 had to stop
therapy; 2 are too early to evaluate, and 1 developed progressive
amyloidosis. No patients had significant coagulation/thrombotic
problems. Of the 26 relapsed/refractory patients, 14 had > 50%
regression (54%). A total of 13 patients had daily Biaxin
(Clarithromycin) added either to improve partial or incomplete
response and/or avert relapse. 9/13 (69%) had added benefit with
induction of no detectable residual disease in 3 patients.
However, because of enhanced steroid toxicity, the
dexamethasone was switched to a 1 day per week schedule, also
used as maintenance for other patients. The limiting toxicity for
all patients was progressive peripheral neuropathy requiring
thalidomide dose reduction or discontinuation of drug, despite
Vitamin B6, alpha lipoic acid and other measures. One patient
developed severe erythroderma after 2 years of thalidomide
maintenance (50mg q.o.d.).
Currently, 22% of the original low dose thalidomide
monotherapy responding patients are alive at > 4 years from start
of therapy. It is too early to assess median time to first
progression with low dose thalidomide/dexamethasone, but it will
exceed 1 year.
Low dose thalidomide combination therapy is very effective and
well tolerated. Durable remissions and long term survival are
achievable.. Further comparisons with higher dose schedules,
with regard to response, toxicity and survival, are required.
326
ThaCyDex in relapsed/refractory multiple myeloma.
Gonzalez-Porras, JR; Garcia-Sanz, R; Polo-Zarzuela, M;
Sureda, A; Barrenetxea, M; Alegre-Amor, A; Grande-
García, C; Pérez R; Gutierrez-Perez, O; Vargas-Pabón, M;
Del Campo, M; Hernandez, J; San Miguel; JF.
Hematology Departament. University Hospital of Salamanca.
Group GEMM. Spain
Introduction: The association of Thalidomide, Cyclophosphamide
and Dexamethasone (ThaCyDex) has been shown to be effective
in a short series of relapsed/refractory multiple myeloma (MM).
However, its real efficacy in large series of patients. has not been
analysed moreover in some of these schemes cyclophosphamide
was used i.v. and toxicity was rather high. In the present work we
have evaluated the efficacy and the tolerability of ThaCyDex in
oral formulations in a series of 59 patients.
Material and methods: The protocol included the administration
of thalidomide at escalating doses (200 to 800 mg/day) according
to its tolerability, daily oral cyclophosphamide (50 mg/day) and
pulsed dexamethasone (40 mg/day, four days every three weeks).
Results: With a median follow-up of 2 years, fifty-four patients
were valuable for response, 5 patients were not valid to evaluate
the response due to early rejection of therapy in two cases, two
cases of thalidomide toxicity and one main protocol violation. At
three months of therapy 47 patients (87%) responded to the
therapy, including 29 cases (57%) with a >50% M-component
reduction (two of them with a complete remission). Only 15
patients have progressed so far, giving a projected progression fee
survival of 65% at 3 years, resulting in a projected overall
survival of 55% at 3 years. Causes of dead were disease
progression (n=10), infection (n=3), sudden death (n=2) and
unknown (n=1). Event free survival was 61%. Adverse effects
were moderate and generally well tolerated. Infection were
recorded in six patients, five patients requiring hospitalisation for
intravenous antibiotic therapy. No cases of thrombocytopenia
grade >2 were noted. Other effects included grades 50 months revealed cytologic evidence of
MDS/sAML two to four months after study entry on bone
marrow specimens obtained for prolonged refractory cytopenia
after chemotherapy. Three of four patients had been pretreated
S234