|
|
BioOncology Watch Timely Information for Practicing
Physicians |
|
|
august 2003 MULTIPLE MYELOMA (MM) Bortezomib therapy of
relapsed and refractory MM. Bortezomib (Velcade; Millennium Pharmaceuticals), a
novel proteasome inhibitor that promotes apoptosis through down-regulation of
NF-kB, has demonstrated activity against MM in preclinical and
phase I studies. Paul Richardson et al
report the results of a multicenter, single-arm trial in which 202 patients
with relapsed MM that was also refractory to their most recent salvage
therapy were administered bortezomib 1.3 mg/m2 intravenously twice
weekly for 2 weeks every 3 weeks. Oral
dexamethasone (20 mg on the day of and the day after an infusion of
bortezomib) was added at the time of disease progression or if the patient
had stable disease after the first 4 cycles of single-agent bortezomib
therapy. The median number of prior
antimyeloma therapies was 6 (range, 2-15) and 64% of patients had previously
received a stem cell transplantation.
Among 193 patients with measurable disease, 27% of patients achieved
at least a partial response (a ³50% reduction in myeloma
paraprotein level) including 4% of patients with a complete response. The median time to progression was 7 months
(13 months for responders) and the median duration of response to single-agent
bortezomib was 12 months (range, 1.3 to 16.7+ months). The median overall survival was 16 months
and according to a landmark analysis, responders to single-agent bortezomib
had a longer survival than nonresponders (p = 0.007). Thirteen (18%) of 74 patients receiving
dexamethasone in addition to bortezomib had at least a minimal response (³25%
reduction in myeloma paraprotein level).
Drug-related adverse events led to discontinuation of bortezomib in 36
(18%) patients and 12% of patients required at least one dose reduction. The most common grade 3 and 4 toxicities
included thrombocytopenia, neutropenia, neuropathy, and fatigue. These data demonstrate that bortezomib is
active in relapsed and refractory MM that is refractory to conventional
chemotherapy. ( NON-SMALL CELL LUNG
CARCINOMA (NSCLC) Gefitinib therapy of
recurrent or refractory NSCLC. Gefitinib (Iressa; Astra Zeneca) is a selective
epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that has
shown activity against advanced NSCLC in early clinical trials. The present study is a multicenter,
randomized, double-blind phase II trial conducted by Masahiro Fukuoka and
associates in which 210 patients with advanced NSCLC previously treated with
1 or 2 chemotherapy regimens (at least one containing platinum) received
either 250-mg or 500-mg oral daily doses of gefitinib. Objective tumor responses rates (18.4% [95%
CI: 11.5-27.3%] and 19.0% [95% CI: 12.1-27.9%]), median progression-free
survival times (2.7 and 2.8 months), and median overall survival times (7.6
and 8.0 months) were similar between the 2 treatment groups. Symptom improvements, as measured by the
Lung Cancer Subscale of the Functional Assessment of Cancer Therapy-Lung
(FACT-L) quality-of-life instrument questionnaire, occurred in 69.2% and
85.7% of the 250 mg/day and 500 mg/day treatment groups, respectively. Gefitinib-related toxicities were generally
mild, but were more frequent in the patients treated with 500 mg/day. Study withdrawal due to gefitinib toxicity
was 1.9% and 9.4% for patients receiving gefitinib 250 and 500 mg/day,
respectively. These data showed that
gefitinib therapy was active against NSCLC and provided symptom relief in
patients with previously treated advanced NSCLC. While efficacy between the 2 treatment
groups was similar, the 250 mg/day dose had the more favorable safety
profile. The authors also noted an
observation that warrants further investigation: adenocarcinoma is a
prognostic factor that may be explained by the relatively slow growth of
adenocarcinoma cells, thus potentially making them more sensitive to
gefitinib. ( CHRONIC MYELOID
LEUKEMIA (CML) High-dose imatinib
mesylate after failure of interferon-a. Imatinib mesylate (Gleevec; Novartis
Pharmaceuticals), a potent tyrosine kinase inhibitor with selectivity against
c-abl and bcr/abl, has been shown to be effective against chronic-phase CML
at doses of 400 mg daily. The results
of early clinical trials have suggested that imatinib dose escalation to 800
mg daily may improve results in selected patients. In the current study, Jorge Cortes and
others at the |
||
|
Produced by Market Development Group through an
educational grant from Genentech, Inc. and IDEC
Pharmaceuticals. Comments and inquiries can be e-mailed to webmaster@biooncologywatch.org |
||