Autocrine growth factors and neuroendocrine markers in the development of small-cell lung cancer.

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 micrograms/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.

Duke Scholars

Author Michael John Kelley Medicine, Medical Oncology