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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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