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Targeted TherapiesÔ Timely
Information for Practicing Hematologists and Oncologists www.tgt-therapies.com |
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MAY 2005 MONOCLONAL ANTIBODY THERAPIES Cetuximab activity against
epidermal growth factor receptor (EGFR)–negative colorectal cancer. Previous studies that enrolled patients whose tumors expressed
EGFR by immunohistochemistry (IHC) have demonstrated cetuximab activity
against metastatic colorectal cancer. In the current study, Ki Young Chung
and colleagues retrospectively reviewed medical records at Rituximab therapy of gastric
extranodal marginal zone (MALT) non-Hodgkin's lymphoma (NHL). Gastric MALT lymphomas are associated with Helicobacter
pylori (HP) infection, for which specific antibiotic therapy results in
complete remission in 60% to 70% of cases. However, 5% to 10% of primary
gastric lymphomas are not associated with HP infection, and approximately 30%
of HP-infected patients develop resistance to antibiotic therapy and/or tumor
relapse. The t(11;18)(q21;q21) translocation has
been shown to confer resistance to antibiotic therapy. In the current study, Giovanni Martinelli and
coworkers used rituximab to treat 27 gastric MALT NHL patients who had
relapsed/refractory disease or were not suitable for anti-HP treatments. Of
26 evaluable patients, 20 (77%) achieved a response (12 complete and 8
partial responses). Only 2 patients relapsed after a median follow-up of 33
months. Cytogenetic findings were not found to correlate with either response
or relapse. Thus, rituximab is active against gastric MALT NHL that is
resistant to antibiotic therapy or presents without HP infection. (Martinelli G, et al. J
Clin Oncol
2005;23:1979–1983) Rituximab plus CHOP chemotherapy
of mantle-cell lymphoma (MCL). George Lenz and others from the
German Low Grade Lymphoma Study Group studied 122 patients with previously
untreated advanced-stage MCL who were randomized to receive rituximab plus
CHOP (R-CHOP) or CHOP chemotherapy alone. Following the achievement of a partial
or complete remission, patients ≤65 years of age underwent a second
randomization to receive myeloablative radiochemotherapy/autologous stem cell
transplantation or interferon alfa maintenance, and patients >65 years of
age received interferon alfa maintenance therapy. No major differences in the safety profiles
of the 2 treatment groups were observed.
R-CHOP was associated with a greater overall response rate (94% vs
75%), complete response rate (34% vs 7%), and median time to treatment
failure (TTF) (21 vs 14 months).
However, no difference was detected for progression-free survival
(PFS) between the 2 groups. These data show that, while R-CHOP improves
response rates and median TTF compared with CHOP alone in patients with MCL,
PFS is not altered. Novel strategies for the treatment of MCL patients in
remission are needed. (Lenz G, et al. J Clin Oncol. 2005;23:1984–1992) Bevacizumab plus erlotinib for
non-small cell lung cancer (NSCLC). Roy Herbst and associates
evaluated the combination of bevacizumab (Avastin®; Genentech) and
erlotinib (Tarcevaä; OSI Pharmaceuticals) in a phase
I/II study of patients with non-squamous stage IIIB/IV NSCLC who had received
at least one prior chemotherapy regimen. No dose-limiting toxicities were
observed, and oral erlotinib 150 mg/day plus bevacizumab 15 mg/kg
intravenously every 21 days was established as the phase II dose. Among 40
patients, 8 patients (20%) achieved a partial response, and 26 patients (65%)
had stable disease as their best response. The median progression-free and
overall survival times were 6.2 and 12.6 months, respectively. The most
common adverse events were mild-to-moderate rash, diarrhea, and proteinuria.
These encouraging findings warrant further investigation of this novel
combination for patients with advanced NSCLC.
(Herbst RS, et al. J Clin Oncol
.2005;23:2544–2555) RADIOIMMUNOTHERAPY Iodine-131–labeled chimeric tumor
necrosis treatment (131I-chTNT). Shaoling Chen and others conducted a
multicenter study in China in which 107 patients with previously treated
advanced lung cancer were treated with intravenously (0.8 mCi/kg) or
intratumorally (0.8 mCi/cm3 tumor volume) injected 131I-chTNT. All
patients received 2 doses of 131I-chTNT administered 2 to 4 weeks apart. Four patients (3.7%) achieved a complete
response, and 33 patients (30.8%) had a partial response. Reversible bone marrow suppression was the
most common toxicity reported. These
results show that 131I-chTNT is active against lung cancer and is well
tolerated. (Chen S, et al. J Clin Oncol.
2005;23:1538–1547) TYROSINE KINASE INHIBITOR Gefitinib in malignant
mesothelioma. Ramaswamy Govindan et al used oral
gefitinib 500 mg/day to treat 43 patients with unresectable pleural or
peritoneal mesothelioma in a CALGB phase II study. Gefitinib was not active
against malignant meso-thelioma, and EGFR expression did not correlate with
failure-free survival. (Govindan R, et al. Clin Cancer Res. 2005;11:2300–2304) REVIEW The editorial board recommends to
readers a recent review of the current state of Targeted Therapy by Mark Pegram et al that appears in the March 10 issue of the Journal
of Clinical Oncology. (Pegram MD, et al. J
Clin Oncol.
2005;23:1776–1781) |
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