A phase I study of nimotuzumab in combination with radiotherapy in stages IIB–IV non-small cell lung cancer unsuitable for radical therapy: Korean results

Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.
Lung cancer (Amsterdam, Netherlands) (Impact Factor: 3.96). 05/2010; 71(1):55-9. DOI: 10.1016/j.lungcan.2010.04.010
Source: PubMed


This study was undertaken to determine safety and tolerability of nimotuzumab, a humanized anti-epidermal growth factor receptor monoclonal antibody, in combination with radiotherapy in stages IIB-IV non-small cell lung cancer (NSCLC) patients who are unsuitable for radical therapy or chemotherapy.
Nimotuzumab (100mg, 200mg and 400mg) was administered weekly from week 1 to week 8 with palliative radiotherapy (30-36 Gy, 3 Gy/day). If tumor control was achieved, nimotuzumab was continued every 2 weeks until unacceptable toxicity or disease progression. Serial skin biopsies were collected for pharmacodynamic assessment.
Fifteen patients were enrolled in the study, with cohorts of five patients assigned in each dose level of nimotuzumab. Patients and disease characteristics included median age 73 years; Eastern Cooperative Oncology Group performance status (PS) 0-1/2 (n=3/12); female sex (n=2); adenocarcinoma (n=5); never-smoker status (n=2); and stages IIB/IIIB/IV (n=1/8/6). All patients were unable to tolerate radical therapy because of old age or multiple comorbidities. The most commonly reported adverse events were lymphopenia and asthenia (grades 1-2 in most patients). No skin rash or allergic toxicities appeared. Dose-limiting toxicity occurred with pneumonia with grade 4 neutropenia at the 200mg dose of nimotuzumab. Objective response rate and disease control rate inside the radiation field were 46.7% and 100.0%, respectively.
Nimotuzumab in combination with radiotherapy is well-tolerated and feasible. Further clinical investigation of nimotuzumab in NSCLC patients is warranted.

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    • "The main advantage of nimotuzumab is that, unlike other EGFR antibodies, it does not cause severe skin toxicity nor does it result in hypomagnesemia or gastrointestinal adverse events.16,19,20 Earlier clinical studies of nimotuzumab plus radiation in patients with stage IIB, IIIB, or IV NSCLC have demonstrated that this combination therapy was well tolerated and feasible for patients unsuitable for radical therapy.21,22 Nimotuzumab combined with gem-citabine and cisplatin was also safe and tolerable in patients with advanced NSCLC.23 "
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    ABSTRACT: Background The purpose of this study was to evaluate the safety and efficacy of nimotuzumab in combination with chemotherapy (docetaxel and carboplatin) versus chemotherapy alone in patients with stage IIIB/IV non-small-cell lung cancer. Methods This multicenter, open-label, Phase II study randomized 110 patients to receive nimotuzumab plus chemotherapy (nimotuzumab group) or chemotherapy alone (control group), and comprised concomitant, maintenance, and follow-up phases. Nimotuzumab 200 mg was administered once weekly for 13 weeks during the first two phases with four cycles of chemotherapy and docetaxel 75 mg/m2 and carboplatin (area under the curve 5 mg/mL*min) every 3 weeks for a maximum of four cycles during the concomitant phase. The primary endpoint was objective response rate (sum of complete response and partial response). Secondary endpoints, ie, overall survival and progression-free survival, were estimated using the Kaplan–Meier method. Efficacy was evaluated on the intent-to-treat and efficacy-evaluable sets. Safety was assessed from adverse event and serious adverse event data. Results The objective response rate was significantly higher in the nimotuzumab group than in the control group in the intent-to-treat population (54% versus 34.5%; P=0.04). A complete response and partial response were achieved in 3.6% and 50% of patients, respectively, in the nimotuzumab group, and in 4% and 30.9% of patients, respectively, in the control group. No significant differences in median progression-free survival and overall survival were observed. Safety profiles were comparable between the two groups. Conclusion Nimotuzumab plus chemotherapy significantly improved the objective response rate as compared with chemotherapy alone. The combination was safe and well tolerated in patients with stage IIIB/IV non-small-cell lung cancer.
    OncoTargets and Therapy 06/2014; 7:1051-60. DOI:10.2147/OTT.S63168 · 2.31 Impact Factor
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    • "These observations have been largely documented in HGG patients, but they are not restricted to brain tumors. Evidence gathered from more than 20,000 patients treated with the antibody in clinical trials and in open populations with advanced tumors, including HNSCC,32,33,72 NSCLC,73,74 and gastrointestinal cancer among others, support the therapeutic efficacy of nimotuzumab.36,75–77 The clinical benefit of nimotuzumab was equivalent or superior to those of other anti-EGFR monoclonal antibodies with a very low incidence of adverse related events (especially skin rash, which accounts for less than 10% of treated patients) making this antibody an appropriate agent that may be efficaciously administered under long-term schedules and in combination with standard cytotoxic therapies.78 "
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    ABSTRACT: Nimotuzumab is a humanized monoclonal antibody that binds specifically to human epidermal growth factor receptor, blocking receptor activation. Evidence of its radiosensitizing capacity has been widely evaluated. This article integrates published research findings regarding the role of nimotuzumab in the treatment of high grade glioma in combination with radiotherapy or radiochemotherapy in adult and pediatric populations. First, the mechanisms of action of nimotuzumab and its current applications in clinical trials containing both radiation and chemoradiation therapies are reviewed. Second, a comprehensive explanation of potential mechanisms driving radiosensitization by nimotuzumab in experimental settings is given. Finally, future directions of epidermal growth factor receptor targeting with nimotuzumab in combination with radiation containing regimens, based on its favorable toxicity profile, are proposed. It is hoped that this review may provide further insight into the rational design of new approaches employing nimotuzumab as a useful alternative for the therapeutic management of high grade glioma.
    OncoTargets and Therapy 07/2013; 6:931-42. DOI:10.2147/OTT.S33532 · 2.31 Impact Factor
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    ABSTRACT: Current non-small cell lung cancer (NSCLC) chemotherapy and radiotherapy regimens, although showing definite survival benefit, still leave patients with a disappointing 15% 5-year overall survival rate. Because of the need to improve traditional outcomes, research has focused on identifying specific tumorigenic pathways that may serve as therapeutic targets. The most successful strategies to date are those aimed at the epidermal growth factor receptor (EGFR), which is found to be upregulated in 40%-80% of NSCLC. Several tyrosine kinase inhibitors and monoclonal antibodies (mAbs) have been developed that inhibit the EGFR receptor and have demonstrated clinical benefit in trials as single agents and in combination regimens. Here we discuss one such agent, the mAb nimotuzumab, the background of its development, its clinical experience in NSCLC thus far, and the rationale for expanding its use to other NSCLC treatment settings.
    Biologics: Targets & Therapy 11/2010; 4:289-98. DOI:10.2147/BTT.S8617
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