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01.03.2009 | Clinical Trial Report

Intensive anti-inflammatory therapy with dexamethasone in patients with non-small cell lung cancer: effect on chemotherapy toxicity and efficacy

verfasst von: Markos Leggas, Kuei-Ling Kuo, Francisco Robert, Gretchen Cloud, Mollie deShazo, Ruiwen Zhang, Mao Li, Hui Wang, Steve Davidson, John Rinehart

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 4/2009

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Abstract

Background

Our preclinical and clinical data suggest that pretreatment with dexamethasone 4 days prior to chemotherapy increased the efficacy and decreased the toxicity of carboplatin and gemcitabine. To translate these findings to patients, we have undertaken a Phase 1/2 clinical trial.

Methods

Thirty patients with advanced non-small cell lung cancer (NSCLC) received gemcitabine, 1,000 mg/m² on days 1 and 8, and carboplatin, AUC 5.5 on day 1. Patients were randomized (1:2:2) to receive, no dexamethasone (cohort 1), or oral dexamethasone at 8 mg (cohort 2) or 16 mg (cohort 3) twice per day, 4 days before and of the day of chemotherapy. Dexamethasone was administered to patients in cohorts 2 and 3 during courses 2–4.

Results

In cohorts 1, 2, and 3, patients completing four planned courses of therapy were: 1/6, 6/12, 9/12. Partial responses (RECIST) were: 2/6, 6/12, and 7/12. Overall, dexamethasone significantly improved AGC and platelet nadirs and recovery times. There were no significant differences in non-hematologic toxicities between cohorts and no significant differences in pharmacokinetic parameters between course 1 and 2 in any cohort.

Conclusions

These data support our previous preclinical and clinical observations that dexamethasone pre-treatment decreases hematopoietic toxicity and improves efficacy of this chemotherapeutic regimen in patients with metastatic non-small cell lung cancer and suggests that further randomized trials should be undertaken.

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Titel: Intensive anti-inflammatory therapy with dexamethasone in patients with non-small cell lung cancer: effect on chemotherapy toxicity and efficacy
verfasst von: Markos Leggas
Kuei-Ling Kuo
Francisco Robert
Gretchen Cloud
Mollie deShazo
Ruiwen Zhang
Mao Li
Hui Wang
Steve Davidson
John Rinehart
Publikationsdatum: 01.03.2009
Verlag: Springer-Verlag
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 4/2009
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-008-0767-x

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Intensive anti-inflammatory therapy with dexamethasone in patients with non-small cell lung cancer: effect on chemotherapy toxicity and efficacy