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Targeted Therapies Timely
Information for Practicing Hematologists and Oncologists www.tgt-therapies.com |
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MARCH 2006 IMATINIB Imatinib plus chemotherapy
in BCR-ABL–positive acute lymphoblastic leukemia (ALL). Imatinib, a selective inhibitor of BCR-ABL
protein kinase, has induced responses in a large proportion of Ph+ chronic phase chronic
myeloid leukemia (CML). Iacobucci and others from the Italian Cooperative Study Group
on CML retrospectively reviewed clinical data obtained from 284 patients
with late chronic phase Ph+ CML who had been treated with imatinib 400
mg/day after the failure of interferon-alpha. They found that after
3 to 4 years of treatment the molecular response of late cytogenetic
responders (patients for whom a complete cytogenetic response was achieved
after 12 months of therapy) was similar to that of early cytogenetic
responders (patients for whom a complete cytogenetic response was achieved
within 12 months of therapy). Moreover, similar estimated rates were
observed for 4-year progression (88% and 100%) and overall survival
(92% and 100%) in early and late responders, respectively. In a second
study, Jabbour and coworkers from the THALIDOMIDE Thalidomide plus dexamethasone
in newly diagnosed multiple myeloma. Rajkumar and associates from the Eastern
Cooperative Oncology Group (ECOG) conducted a phase III study in which
207 patients with newly diagnosed multiple myeloma were randomized to
receive oral thalidomide 200 mg/day plus oral high-dose dexamethasone
40 mg on days 1 through 4, 9 through 12, and 17 through 20 every 4 weeks,
or dexamethasone alone. Patients were expected to discontinue the study
after four cycles to undergo autologous stem cell transplantation, but
treatment beyond four cycles was permitted at the discretion of the
treating physician. The response rate in the thalidomide plus dexamethasone
arm was greater than that observed in the dexamethasone-alone arm (63%
vs 41%). Deep vein thrombosis (DVT) occurred more frequently in patients
treated with combination therapy than in patients treated with dexamethasone
alone (17% vs 3%). The incidence of DVT of grade 3 or above, neuropathy,
rash, bradycardia, and any grade 4 to 5 toxicity was higher in the combination
therapy group than in the dexamethasone-alone group (45% vs 21%). These
data show that the higher response rate achieved with thalidomide plus
dexamethasone compared with dexamethasone alone in newly diagnosed patients
with multiple myeloma must be weighed against the greater toxicity associated
with the combination. (Rajkumar SV, et al. J Clin Oncol. 2006;24:431–436.) CHRONIC LYMPHOCYTIC LEUKEMIA
(CLL) High-risk genetic features
predict poor outcomes. Byrd and others examined the impact of new prognostic factors
on outcomes of 88 symptomatic, previously untreated CLL patients who
received fludarabine and rituximab in a randomized phase II study. The
new prognostic factors predicting rapid CLL disease progression included
unmutated IgVH, OVARIAN CANCER Yttrium-90-labeled HMFG1
murine monoclonal antibody therapy. A preliminary study of yttrium-90-labeled murine HMFG1 administered
once intraperitoneally (IP) showed prolonged disease-free survival in
CR patients with epithelial ovarian cancer (EOC) after surgical debulking
and chemotherapy. Verheijen and colleagues conducted a phase III trial
in which 447 patients with EOC but no evidence of macroscopic disease
following surgery and chemotherapy were randomized to receive IP yttrium-90-labeled
murine HMFG1 monoclonal antibody or standard care. At a median follow-up
of 3.5 years, no differences in time to relapse or survival were noted
between treatment arms. This study showed that consolidation therapy
with yttrium-90-labeled murine HMFG1 monoclonal antibody in EOC patients
after surgically defined CR was not effective. (Verheijen RH, et al.
J Clin Oncol. 2006;24:571–578.) |
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