Cetuximab治疗非小细胞肺癌的进展

表皮生长因子受体(EGFR)在非小细胞肺癌(NSCLC)患者中存在过表达.Cetuxumab(C225,erbitux)是一种单克隆抗体,可竞争性结合EGFR细胞外配体区,抑制肿瘤生长,与放化疗有协同作用.本文综述cetuxumab联合放化疗治疗晚期NSCLC的临床前和临床资料,显示出cetuxumab具有良好耐受性.     

Combined treatment of nonsmall cell lung cancer NSCLC stage III with intensity-modulated RT radiotherapy and cetuximab: the NEAR trial

BACKGROUND:

The aim of this study was to evaluate efficacy and toxicity of radioimmunotherapy with intensity‐modulated radiation (IMRT) and cetuximab in stage III nonsmall cell lung cancer (NSCLC).

METHODS:

NEAR was a prospective, monocentric phase II trial including patients unfit for chemoradiation regimen; treatment consisted of IMRT and weekly cetuximab followed by a 13‐week maintenance period. Primary endpoints were toxicity and feasibility; secondary endpoints were remission rates at completion of the planned treatment according to Response Evaluation Criteria In Solid Tumor (RECIST), local/distant progression‐free survival, and overall survival.

RESULTS:

Thirty patients (median age, 71 years) were treated within the protocol. Overall response rate was 63% (partial remission: 19 of 30) patients. Median locoregional, distant, overall progression‐free survival was 20.5, 10.9, and 8.5 months. Median overall survival was 19.5 months, with an estimated 1‐ and 2‐year survival of 66.7% and 34.9% respectively. Stage (IIIA vs IIIB) and histologic subtype did not have a significant impact on survival rates in our patients. Treatment was tolerated well with only mild toxicity (°3 pneumonitis: 3.3%, any °3 acute toxicity: 36.7%).

CONCLUSIONS:

Combined radioimmunotherapy with cetuximab was safe and feasible, especially in elderly patients with multiple comorbidities. A more intensified regimen warranted investigation. Cancer 2011. © 2011 American Cancer Society.     

Clinical impact of anti-epidermal growth factor receptor monoclonal antibodies in first-line treatment of metastatic colorectal cancer: meta-analytical estimation and implications for therapeutic strategies

BACKGROUND:

Antiepidermal growth factor receptor (anti‐EGFR) monoclonal antibodies (MoAbs) are indicated for the treatment of metastatic colorectal cancer patients, but some scientific issues concerning their efficacy are currently unsolved.

METHODS:

A literature‐based meta‐analysis was conducted. Hazard ratios (HRs) were extracted from randomized trials for progression‐free survival (PFS) and overall survival (OS); the event‐based risk ratio was derived for response. Sensitivity analyses to look for interactions according to KRAS status and chemotherapy association regimens were performed.

RESULTS:

Eight trials (6609 patients) were identified. A significant interaction according to KRAS status was found for PFS (wild type vs mutant, P = .001) and response rate (wild type vs mutant, P < .0001). The addition of an anti‐EGFR MoAb to first‐line chemotherapy increased PFS in the KRAS wild‐type population (HR, 0.91; 95% confidence interval [CI], 0.84‐0.99; P = .03), and had a detrimental effect in the KRAS mutant population (HR, 1.13; 95% CI, 1.03‐1.25; P = .013). A significant increase in the probability of achieving a response was evident in KRAS wild‐type patients (relative risk, 1.17; 95% CI, 1.04‐1.33; P = .011). In this population, the interaction in response rate according to adopted chemotherapy favored irinotecan‐containing regimens (P = .01), and at meta‐regression analysis the relative increase in response rate was significantly related to PFS (P = .00001) and OS (P = .00193) benefit.

CONCLUSIONS:

The addition of an anti‐EGFR MoAb to first‐line chemotherapy produces a clear benefit in response rate. This advantage is restricted to KRAS wild‐type patients and translates into a small benefit in PFS. At present, irinotecan‐based backbone chemotherapy could be a preferable option. The correlation between activity and survival parameters corroborates the hypothesis that anti‐EGFR MoAbs might be more suitable for patients needing tumoral shrinkage. Cancer 2011;. © 2011 American Cancer Society.     

Psoriasis induced by cetuximab: a paradoxical adverse effect

Cetuximab, an epidermal growth factor receptor inhibitor, is a chemotherapeutical agent featuring well-known adverse dermatological effects related to tumour-response prognosis. In psoriasis, the epidermal growth factor receptor is overexpressed; hence, the expectation would be that an epidermal growth factor receptor inhibitor could improve psoriatic lesions. We report a case of psoriasis induced by cetuximab, which was a surprising adverse effect.     

Cetuximab in metastatic colorectal cancer

Management of metastatic colorectal cancer has evolved in the last 10 years, with the availability of targeted therapies resulting in improvement in quality of life and overall survival. Cetuximab is a chimeric monoclonal antibody that binds to the EGF receptor, and the net effects are inhibition of tumor growth, invasion, angiogenesis and metastasis. Cetuximab binding to the EGF receptor is also known to augment the effects of chemotherapy and radiotherapy. Only tumors expressing wild-type KRAS respond to cetuximab and improvements in progression-free survival and overall survival are seen, whereas patients with mutant KRAS are considered to be resistant. Cetuximab is currently available worldwide for use as monotherapy or in combination with chemotherapy in first-, second- or third-line settings in metastatic colorectal cancer patients with wild-type KRAS.     

Systemic treatment strategies and therapeutic monitoring for advanced nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is endemic in Asia and is etiologically associated with the Epstein–Barr virus. Although radiotherapy can cure most patients with early-stage disease, those with advanced disease often develop recurrences following radiotherapy. The past decade has witnessed significant advances in the systemic treatment of advanced NPC. This article reviews the latest literature regarding: combined modality therapy for locoregionally advanced NPC; clinical trials of novel biologic and cytotoxic therapies for metastatic NPC; and disease monitoring with the plasma Epstein–Barr virus DNA assay.     

Contradictory KRAS mutation test results in a patient with metastatic colon cancer: A clinical dilemma in the era of personalized medicine

The KRAS oncogene is mutated in 40‒50% of colorectal cancers and confers resistance to EGFR-targeted therapy. In the clinic, agents such as cetuximab or panitumumab target the EGFR receptor for therapeutic benefit. Cetuximab was approved by the FDA in 2012 as first-line therapy for KRAS mutation-negative (wild-type), EGFR-expressing metastatic colorectal cancer, in combination with FOLFIRI (5-fluorouracil, irinotecan, leucovorin). Herein we report a case of metastatic colon cancer with conflicting testing results for the KRAS oncogene from two different reference laboratories. The discordant reports complicated the decision-making process regarding the administration of targeted anti-EGFR personalized therapy. As the second test result was wild-type from the same original pathological specimen, the patient was treated with cetuximab-containing combination chemotherapy and appeared to have a response after prior disease progression. It is unclear whether the observed response was fully due to regression of wild-type KRAS-containing tumor or any component of antibody-dependent cellular cytotoxicity to a heterogeneous tumor in this patient.