A randomized, multicenter study to determine the safety and efficacy of the immunoconjugate SGN-15 plus docetaxel for the treatment of non-small cell lung carcinoma

Chemotherapy prolongs survival and improves quality of life (QOL) for good performance status (PS) patients with advanced non-small cell lung cancer (NSCLC). Targeted therapies may improve chemotherapy effectiveness without worsening toxicity. SGN-15 is an antibody–drug conjugate (ADC), consisting o...

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Bibliographic Details
Published in:Lung cancer (Amsterdam, Netherlands) Netherlands), 2006-10, Vol.54 (1), p.69-77
Main Authors: Ross, Helen J., Hart, Lowell L., Swanson, Paul M., Rarick, Mark U., Figlin, Robert A., Jacobs, Andrew D., McCune, David E., Rosenberg, Arthur H., Baron, Ari D., Grove, Laurie E., Thorn, Michael D., Miller, Dennis M., Drachman, Jonathan G., Rudin, Charles M.
Format: Article
Language:English
Subjects:
Adult
Aged
Animals
Antibodies, Monoclonal - adverse effects
Antibodies, Monoclonal - pharmacokinetics
Antibodies, Monoclonal - therapeutic use
Antineoplastic Agents, Phytogenic - adverse effects
Antineoplastic Agents, Phytogenic - pharmacokinetics
Antineoplastic Agents, Phytogenic - therapeutic use
Biological and medical sciences
Carcinoma, Non-Small-Cell Lung - drug therapy
Female
Humans
Immunoconjugate
Immunoconjugates - adverse effects
Immunoconjugates - pharmacokinetics
Immunoconjugates - therapeutic use
Lewis Y
Lung Neoplasms - drug therapy
Male
Medical sciences
Mice
Middle Aged
Monoclonal antibody
NSCLC
Pneumology
Quality of Life
SGN-15
Survival Rate
Targeted therapy
Taxoids - adverse effects
Taxoids - pharmacokinetics
Taxoids - therapeutic use
Treatment Outcome
Tumors of the respiratory system and mediastinum
United States
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Summary:Chemotherapy prolongs survival and improves quality of life (QOL) for good performance status (PS) patients with advanced non-small cell lung cancer (NSCLC). Targeted therapies may improve chemotherapy effectiveness without worsening toxicity. SGN-15 is an antibody–drug conjugate (ADC), consisting of a chimeric murine monoclonal antibody recognizing the Lewis Y (Le y) antigen, conjugated to doxorubicin. Le y is an attractive target since it is expressed by most NSCLC. SGN-15 was active against Le y-positive tumors in early phase clinical trials and was synergistic with docetaxel in preclinical experiments. This Phase II, open-label study was conducted to confirm the activity of SGN-15 plus docetaxel in previously treated NSCLC patients. Sixty-two patients with recurrent or metastatic NSCLC expressing Le y, one or two prior chemotherapy regimens, and PS ≤ 2 were randomized 2:1 to receive SGN-15 200 mg/m 2/week with docetaxel 35 mg/m 2/week (Arm A) or docetaxel 35 mg/m 2/week alone (Arm B) for 6 of 8 weeks. Intrapatient dose-escalation of SGN-15 to 350 mg/m 2 was permitted in the second half of the study. Endpoints were survival, safety, efficacy, and quality of life. Forty patients on Arm A and 19 on Arm B received at least one treatment. Patients on Arms A and B had median survivals of 31.4 and 25.3 weeks, 12-month survivals of 29% and 24%, and 18-month survivals of 18% and 8%, respectively. Toxicity was mild in both arms. QOL analyses favored Arm A. SGN-15 plus docetaxel is a well-tolerated and active second and third line treatment for NSCLC patients. Ongoing studies are exploring alternate schedules to maximize synergy between these agents.
ISSN:0169-5002
1872-8332
DOI:10.1016/j.lungcan.2006.05.020