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

Abstract

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.

• Authors: M J Kelley, R I Linnoila, I L Avis, M S Georgiadis, F Cuttitta, J L Mulshine, B E Johnson
• Journal: Chest (Chest) Vol. 112 Issue 1 Pg. 256-61 (Jul 1997) ISSN: 0012-3692 [Print] United States
• PMID: 9228385 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article)

Chemical References

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

Topics

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