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.
Johnson
B E
BE
Division of Clinical Sciences, National Naval Medical Center, USA.
Kelley
M J
MJ
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018288:Carcinoma, Small Cell / Q000000981:diagnostic imaging / Q000628:therapy*; D005260:Female; D019886:Gastrin-Releasing Peptide / Q000276:immunology*; D006801:Humans; D018796:Immunoconjugates; D000922:Immunotoxins / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000628:therapy*; D008297:Male; D019006:Neural Cell Adhesion Molecules / Q000276:immunology*; D011859:Radiography; D012276:Ricin / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D018796:Immunoconjugates; D000922:Immunotoxins; C080540:N901 MoAb-blocked ricin conjugate; D019006:Neural Cell Adhesion Molecules; D019886:Gastrin-Releasing Peptide; D012276:Ricin