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

  • Clinical Trial Report
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Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

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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Acknowledgments

This work was supported by a grant from Eli Lilly and Company (JJR) and by the Buck-Kentucky Lung Cancer Research Chair (JJR). Funding was also provided by the Markey Cancer Center and the Markey Foundation (ML)

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Authors and Affiliations

  1. The Markey Cancer Center, Division of Hematology, Oncology, Blood and Marrow Transplantation and the Experimental Therapeutics Program, University of Kentucky, Lexington, KY, USA

    John Rinehart

  2. The College of Pharmacy, Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY, USA

    Markos Leggas & Kuei-Ling Kuo

  3. The Division of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, AL, USA

    Francisco Robert, Gretchen Cloud & Mollie deShazo

  4. Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL, USA

    Ruiwen Zhang, Mao Li & Hui Wang

  5. The Montgomery Cancer Center, Montgomery, AL, USA

    Steve Davidson

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  1. Markos Leggas
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Correspondence to John Rinehart.

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Leggas, M., Kuo, KL., Robert, F. et al. Intensive anti-inflammatory therapy with dexamethasone in patients with non-small cell lung cancer: effect on chemotherapy toxicity and efficacy. Cancer Chemother Pharmacol 63, 731–743 (2009). https://doi.org/10.1007/s00280-008-0767-x

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