Antitumor activity of a monoclonal antibody directed against gastrin-releasing peptide in patients with small cell lung cancer

Chest. 1997 Jul;112(1):256-61. doi: 10.1378/chest.112.1.256.


Background: Small cell lung cancer (SCLC) cells express and secrete gastrin-releasing peptide (GRP) which binds to receptors and stimulates growth of these cells. A murine monoclonal antibody, 2A11, which binds GRP with high affinity, decreased growth of SCLC cells in vitro and in athymic nude mice. A phase 1 trial and pharmacokinetic modeling in patients with lung cancer has defined the phase 2 dose of 2A11 but the antitumor activity in patients is unknown.

Methods: Thirteen patients with previously treated SCLC received 2A11 at 250 mg/m2 over 1 h three times per week for 4 weeks. Serum GRP, urine GRP, serum levels of 2A11, and human antimouse antibodies (HAMA) were determined.

Results: One of 12 (8%; 95% confidence interval, 0 to 38%) evaluable patients had complete resolution of radiographically detectable tumor lasting 4 months. Four patients (33%) had stable disease. No toxic reactions were observed. The pretreatment serum GRP level of the responding patient was 3.1 fmol/mL and the median of nine nonresponding patients was 7.3 fmol/mL (range, <1.0 to 29.0). The mean trough serum 2A11 level was 49+/-18 microg/mL in the responding patient and 32 to 487 mg/mL (median, 117) in 10 nonresponding patients. HAMA did not increase during 2A11 administration in any patient.

Conclusions: Interruption of the GRP autocrine growth factor loop with 2A11 results in clinical antitumor activity in a minority of patients with previously treated SCLC. Further evaluation of the antitumor effects of 2A11 is warranted to define characteristics associated with response to 2A11.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / pharmacokinetics
  • Antibodies, Monoclonal / therapeutic use*
  • Bombesin / immunology*
  • Carcinoma, Small Cell / therapy*
  • Female
  • Gastrin-Releasing Peptide
  • Humans
  • Lung Neoplasms / therapy*
  • Male
  • Mice
  • Mice, Nude
  • Middle Aged
  • Peptides / immunology*


  • Antibodies, Monoclonal
  • Peptides
  • Gastrin-Releasing Peptide
  • Bombesin