Autocrine Growth Factors and Neuroendocrine Markers in the Development of Small-Cell Lung Cancer

ABSTRACT: Two different clinical trials using biological agents directed against an autocrine growth factor and a surface marker of neuroendocrine differentiation have been used for patients with relapsed small-cell lung cancer. In a phase II trial, an antibody (2A11) directed against the autocrine growth factor gastrin-releasing peptide has been used to treat patients with relapsed small-cell lung cancer. One of 12 evaluable patients treated with 2A11 250 mg/m² three times weekly for 4 weeks achieved a complete response. An antibody directed against the neural cell adhesion molecule has been linked to a modified ricin molecule. This immunotoxin, N901-bR, has undergone phase I testing, and a recommended phase II dose of 30 mg/kg/day for 7 days by continuous infusion has been determined. In the phase I trial, one of 21 patients with relapsed or refractory small-cell lung cancer had a partial response to this treatment. Therefore, it appears that an antibody directed against an autocrine growth factor and an immunotoxin directed against a surface marker of neuroendocrine differentiation can inhibit the growth of small-cell lung cancer in vitro and in vivo; both produced some evidence of antitumor activity in patients. Further studies with agents directed against autocrine growth factors and surface markers of neuroendocrine differentiation appear warranted. [ONCOLOGY 12(Suppl 2):11-14, 1998]

Human lung cancers are divided both clinically and biologically into small-cell lung cancer and non-small-cell lung cancer, each having distinctive histologic, clinical, and biologic features.[1] One distinguishing feature is that small-cell lung cancer more commonly has markers of neuroendocrine differentiation than are seen with non-small-cell lung cancer. These markers may include enzymatic activity, such as L-dopa decarboxylase and neuron-specific enolase, peptide hormones, including arginine vasopressin and gastrin-releasing peptide, and surface markers, such as the neural cell adhesion molecule. These autocrine growth factors and markers of neuroendocrine differentiation in small-cell lung cancer provide distinguishing biologic characteristics for the development of novel therapies. Presented here are data from two clinical trials[2,3] in which patients with small-cell lung cancer were treated using biologic agents directed against an autocrine growth factor or a surface marker of neuroendocrine differentiation.

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