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Clinical Cancer Research Vol. 9, 1077-1082, March 2003
© 2003 American Association for Cancer Research

Molecular Oncology, Markers, Clinical Correlates

{alpha}-1-Acid Glycoprotein As an Independent Predictor for Treatment Effects and a Prognostic Factor of Survival in Patients with Non-small Cell Lung Cancer Treated with Docetaxel1

René Bruno2, Robert Olivares3, Jocelyne Berille, Philip Chaikin4, Nicole Vivier, Luz Hammershaimb5, Gerald R. Rhodes6 and James R. Rigas

Aventis Pharma, Drug Metabolism and Pharmacokinetics [R. B., N. V., G. R. R.], Statistics [R. O.], and Clinical Research Department [J. B., P. C., L. H.], 92165 Antony cedex, France and Collegeville, Pennsylvania, and Comprehensive Thoracic Oncology Program, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire [J. R. R.]

Purpose: To identify predictors of treatment outcome and survival in patients with non-small cell lung cancer (NSCLC) treated with docetaxel.

Experimental design: The data were collected from 180 NSCLC patients enrolled in six docetaxel Phase II studies at a dose of 100 mg/m2. Clinical end points for this study were safety reported as the first course adverse events requiring dose reduction, and efficacy was measured by response rate and survival. The independent variables included docetaxel dose, individual estimates of clearance, area under the plasma concentration time curve, extent of previous treatment, and covariables related to the patient’s demographics, extent of disease, and performance status. The data were analyzed using a logistic regression model for response and severe adverse events and a Cox multivariate regression model for survival.

Results: Docetaxel exposure as measured by the area under the plasma concentration time curve was the only significant predictor (P < 0.0001) of severe toxicity during the first course of therapy. Baseline {alpha}1-acid glycoprotein (AAG) was the only significant predictor of response with an odds ratio of 0.44 for changes in AAG from 1.11 to 1.85 grams/liter (P = 0.0039). Cumulative dose, AAG, and extent of disease were independent predictors of survival (P < 0.005). The median survival varied from 15.6 months for patients with a low AAG (AAG <= 1.11 grams/liter) to 5.5 months for patients with a high AAG (AAG >= 1.85 grams/liter).

Conclusion: AAG appears to be an independent predictor of response and a major objective prognostic factor of survival in patients with NSCLC treated with docetaxel chemotherapy.




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Molecular Cancer Research Cancer Prevention Research
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Copyright © 2003 by the American Association for Cancer Research.