|
|
BioOncology Watch Timely Information for Practicing
Physicians |
|
|
december 2003 ERYTHROPOIETIN Treatment of anemia
in patients with head and neck cancer.
Michael Henke et al reported a
randomized, double-blind, placebo-controlled trial to determine if
erythropoietin could improve cancer control and survival in 351 patients irradiated for head and neck
cancer. Eligible radiotherapy patients
(blood hemoglobin concentrations <120 g/L for women and <130 g/L for
men) were randomized to receive either epoetin b 300
IU/kg (n = 180) or placebo (n = 171) 3 times weekly beginning 10-14 days
before and continuing throughout radiotherapy. Patients were stratified by tumor resection
status: stratum 1, completely resected; stratum 2, incompletely resected; stratum 3,
unresectable. Locoregional
progression-free survival was poorer in epoetin b-treated
patients than in placebo-treated patients. Analysis by stratum revealed that
locoregional
progression-free survival was similar between the treatment groups for
stratum 1 patients, but stratum-2 and -3 patients fared worse when given epoetin
b than when given placebo. Overall survival decreased in the epoetin b treatment group compared to the placebo group. These findings demonstrated that while
anemia was corrected by epoetin b
therapy, disease control was impaired in epoetin b-treated
patients with head and neck cancer undergoing irradiation. These findings are consistent with recent
observations of the BEST Investigators and Study Group (Leyland-Jones. Lancet Oncology 2003;4:459-460 [letter]). An Independent Data Monitoring Committee
terminated this trial early because metastatic breast cancer patients given
erythropoietin plus first-line chemotherapy were found to have lower 12-month
survival rates than patients receiving placebo plus first-line
chemotherapy. (Henke M, et al. Lancet 2003;262:1255-1260) RITUXIMAB Mechanism of
action. Wen-Kai Weng and Ronald Levy performed in vitro
antibody-dependent cellular cytotoxicity (ADCC) assays on pretreatment tumor
cells from 87 patients with follicular lymphoma subsequently treated with rituximab
between 1993 and 2003. No
difference in susceptibility of tumor cells to rituximab-mediated ADCC was
found between patients who did or did not respond to rituximab therapy. However, subgroup analyses showed that both
the FcgRIIIa 158 valine/valine and FcgRIIa 131 histidine/histidine genotypes were independently associated with
clinical responses to rituximab and increased progression-free survival. This
study supports the notion that ADCC plays an important role in the clinical
effect of rituximab. Analysis of Fc
receptor polymorphisms in future trials of rituximab therapy is needed. (Weng W-K and Levy R. J Clin Oncol 2003; 21:3940-3947) Downmodulation of
CD20 in chronic lymphocytic leukemia (CLL) patients. Iman Jiliani and colleagues analyzed peripheral blood samples from 65
patients with CLL treated with rituximab and demonstrated that rituximab was
detectable on the lymphocytes of only 3 patients despite the fact that most
patients had become CD20-negative.
However, rituximab binding to the CD20 antigen on the surface of CLL
cells was detectable when CLL cells were mixed with rituximab. Rituximab subsequently became undetectable
when plasma was added due to a down-modulation of the expression of both CD20
antigen and mRNA. The CLL cells regained CD20 expression after 24 hours in
culture. These experiments indicated
that rituximab did not mask expression of CD20 on CLL cells. Instead, rituximab therapy, in the presence
of plasma, was observed to cause a transient down-modulation of CD20 expression
on CLL cells. Further studies are needed to elucidate the importance of this
finding. Extrapolation of these
results to other lymphomas cannot be done at this time due to a lack of data. (Jiliani I, et al. Blood 2003;102:3514-3520) TRASTUZUMAB Every 3 weeks
administration in combination with paclitaxel. Brian Leyland-Jones et al evaluated the pharmacokinetics and safety of
trastuzumab plus paclitaxel given every 3 weeks to 32 women with
HER-2-overexpressing metastatic breast cancer. Patients received paclitaxel 175 mg/m2
i.v. on Day 0 and a loading dose of 8 mg/kg of trastuzumab on Day 1.
Thereafter, trastuzumab 6 mg/kg and paclitaxel 175 mg/m2 were
administered i.v. every 3 weeks for up to 7 cycles. Trastuzumab-related
adverse events included infusion reactions and cardiac dysfunction, and ≥
15% decreases in ejection fraction occurred in 10 patients. Objective
responses were achieved in 59% of patients and 22% had stable disease.
Median duration of response was 10.5 months; median time to
progression was 12.2 months. Thus, administration of trastuzumab every 3
weeks in combination with paclitaxel resulted in clinical response rates that
compared favorably with those of standard weekly trastuzumab plus
chemotherapy. Further study of
higher-dose 3-week trastuzumab regimens is warranted. (Leyland-Jones B, et
al. J Clin Oncol 2003;21:3965-3971) IMATINIB MESYLATE Risk and prognosis
of central nervous system (CNS) leukemia.
Heike Pfeifer et al analyzed 107
patients with relapsed or refractory |
||
|
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 |
||