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Targeted Therapies Formerly BioOncology
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SEPTEMBER 2005 NON-SMALL-CELL LUNG CANCER (NSCLC) Erlotinib; clinical and molecular
results. Two reports
from the National Cancer Institute of Canada (NCIC) detail the clinical
results (Shepherd and colleagues) and molecular results (Tsao
and colleagues) of a randomized, double-blind trial comparing the epidermal
growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib with
placebo. The study population consisted of 731 patients with advanced NSCLC
who had received one or two prior chemotherapy regimens (platinum-based in
93% of patients). An objective response was achieved in 8.9% of
erlotinib-treated patients compared with <1% of placebo patients (P <0.001). The median duration of
response to erlotinib was 7.9 months, and progression-free survival was 2.2
months in the erlotinib group and 1.8 months in the placebo group (P <0.001). Median overall survival
was greater in patients treated with erlotinib than in patients who received
placebo (6.7 vs 4.7 months; P <0.001).
Multivariate analysis showed that adenocarcinoma, lack of a smoking history,
and expression of EGFR were associated with tumor response but not overall
survival. Rash and diarrhea were the most frequent causes of erlotinib dose
reductions (reported in 19% of patients), but only 5% of patients permanently
discontinued erlotinib due to adverse events. These results demonstrate that
erlotinib can prolong survival in patients with previously treated NSCLC. (Shepherd
FA, et al. N Engl J Med.
2005;353:123–132 and Tsao M-S, et al. N Engl J Med. 2005;353:133–144.) BREAST CANCER Trastuzumab plus docetaxel. Marty and associates conducted a
multicenter study in which 186 patients with previously untreated HER-2–positive
metastatic breast cancer were randomized to receive six cycles of docetaxel
(100 mg/m2 every 3 weeks) plus trastuzumab (4 mg/kg loading dose
followed by 2 mg/kg weekly until disease progression) or six cycles of
docetaxel alone. Combination therapy yielded a response rate of 61% compared with
34% with docetaxel alone. Median duration of response (11.7 vs 5.7 months),
time to progression (11.7 vs 6.1 months), and overall survival time (31.2 vs
22.7 months) were greater in patients treated with trastuzumab plus docetaxel
compared with docetaxel alone. Grade NON-HODGKIN'S LYMPHOMA Phase I/II study of galiximab. Galiximab is a monoclonal antibody
directed against CD80, a membrane bound co-stimulatory
molecule constitutively expressed on a variety of lymphomas. Czuczman and coworkers performed a multicenter,
dose-finding study of galiximab in 37 patients with relapsed or refractory
follicular lymphoma. Four weekly infusions of galiximab 125, 250, 375, or 500
mg/m2 were administered. The overall response rate was 11% (two
complete and two partial responses), and 12 patients maintained stable
disease. Two responders had not developed disease progression at 22 and 24.4
months of follow-up, respectively. The most common adverse events associated
with galiximab were grade 1 or 2 fatigue, nausea, and headache. The
development of anti-galiximab antibodies was not observed. These data
demonstrate that galiximab has a favorable safety profile and is active
against follicular lymphoma. (Czuczman MS, et al. J Clin Oncol. 2005;23:4390–4398.) HODGKIN'S DISEASE Treatment with radioimmunotherapy.
CD30, a
lymphocyte activation marker, is expressed in high numbers on the malignant
cells of Hodgkin's disease. This finding led Schnell
and others to develop a radioimmunoconjugate consisting of a murine anti-CD30
monoclonal antibody (Ki-4) labeled with iodine-131 (131I). Twenty-two
patients with relapsed or refractory CD30-positive Hodgkin's disease were
treated with 131I-Ki-4. A preinfusion of
native Ki-4 5 mg was found to be sufficient to bind soluble CD30. The
therapeutic dose of 131I-Ki-4 was given 1 week after the infusion
of unlabeled Ki-4. Whole-body scintigraphy demonstrated uptake of the
radioimmunoconjugate in four patients with tumor masses >5 cm and one patient
with a thoracic mass of 2.5 cm. Tumor visualization was difficult due to the
limited resolution of the gamma camera, the modest uptake of 131I-Ki-4,
and the adjacent blood pool activity. Six patients achieved an objective
response and three patients had minor responses. Seven patients experienced
grade 4 neutropenia or thrombocytopenia 4 to 8 weeks after treatment. These
results indicate 131I-Ki-4 is a potentially effective treatment
against relapsed or refractory Hodgkin's disease. (Schnell
R, et al. J Clin
Oncol. 2005;23:4669–4678.) Post-transplantation imatinib
therapy. The
detection of minimal residual disease (MRD) following stem cell transplantation
(SCT) in patients with Ph+ ALL is associated
with a relapse risk of >90%. Wassman and colleagues
treated 27 patients who had Ph+ ALL with
imatinib upon detection of MRD after SCT. The starting dose of imatinib was
400 mg/d, and dose escalation to 800 mg/d was permitted for patients who
remained bcr-abl–positive. Bcr-abl
transcripts became negative by polymerase chain reaction (PCR) assay in 14
patients (52%) after a median of 1.5 months (0.9 to 3.7 months) of imatinib
therapy. The disease-free and overall survival rates were 91% ± 9% and 100%,
respectively, at 1 year for patients who became MRD-negative with imatinib
treatment compared with 8% ± 7% and 23% ± 13%, respectively, at 13 months in
patients who remained MRD-positive. These data demonstrate that an early
complete molecular remission induced by imatinib in MRD-positive patients
with Ph+ ALL following SCT is associated
with improved clinical outcomes. Patients in whom bcr-abl
transcripts continue to be detected after approximately 3 months of imatinib
therapy require additional/alternative antileukemic treatment. (Wassman B, et al. Blood.
2005;106:458–463.) |
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