Targeted TherapiesÔ

Timely Information for Practicing Hematologists and Oncologists

www.tgt-therapies.com

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 Memorial Sloan-Kettering Cancer Center to identify colorectal cancer patients whose pathology report indicated an EGFR-negative tumor by IHC and who had failed prior irinotecan-based chemotherapy and had received cetuximab. In total, 16 patients were identified who fulfilled these criteria. Pathology slides were reviewed by a reference pathologist to confirm EGFR negativity, and computed tomography scans were reviewed by a reference radiologist to confirm responses. Of the 16 patients, 14 patients received cetuximab plus irinotecan, and 2 patients received single-agent cetuximab. Among these 16 patients, 4 patients (25%) achieved an objective tumor response (95% CI: 4–46%). These findings suggest that EGFR analysis by current IHC techniques does not predict for response to cetuximab therapy.  (Chung KY, et al. J Clin Oncol. 2005;23:1803–1810)

 

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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