Toxicity profile of the immunomodulatory thalidomide analogue, lenalidomide : Phase I clinical trial of three dosing schedules in patients with solid malignancies

Sharma, R. A., Steward, W. P., Daines, C. A., Knight, R. D., O'Byrne, Kenneth J., & Dalgleish, A. G. (2006) Toxicity profile of the immunomodulatory thalidomide analogue, lenalidomide : Phase I clinical trial of three dosing schedules in patients with solid malignancies. European Journal of Cancer, 42(14), pp. 2318-2325.

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Thalidomide is an anti-angiogenic agent currently used to treat patients with malignant cachexia or multiple myeloma. Lenalidomide (CC-5013) is an immunomodulatory thalidomide analogue licensed in the United States of America (USA) for the treatment of a subtype of myelodysplastic syndrome. This two-centre, open-label phase I study evaluated dose-limiting toxicities in 55 patients with malignant solid tumours refractory to standard chemotherapies. Lenalidomide capsules were consumed once daily for 12 weeks according to one of the following three schedules: (I) 25 mg daily for the first 7 d, the daily dose increased by 25 mg each week up to a maximum daily dose of 150 mg; (II) 25 mg daily for 21 d followed by a 7-d rest period, the 4-week cycle repeated for 3 cycles; (III) 10 mg daily continuously. Twenty-six patients completed the study period. Two patients experienced a grade 3 hypersensitivity rash. Four patients in cohort I and 4 patients in cohort II suffered grade 3 or 4 neutropaenia. In 2 patients with predisposing medical factors, grade 3 cardiac dysrhythmia was recorded. Grade 1 neurotoxicity was detected in 6 patients. One complete and two partial radiological responses were measured by computed tomography scanning; 8 patients had stable disease after 12 weeks of treatment. Fifteen patients remained on treatment as named patients; 1 with metastatic melanoma remains in clinical remission 3.5 years from trial entry. This study indicates the tolerability and potential clinical efficacy of lenalidomide in patients with advanced solid tumours who have previously received multi-modality treatment. Depending on the extent of myelosuppressive pre-treatment, dose schedules (II) or (III) are advocated for large-scale trials of long-term administration. © 2006 Elsevier Ltd. All rights reserved.

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ID Code: 65686
Item Type: Journal Article
Refereed: Yes
Additional URLs:
Keywords: Chemotherapy, Cytokine, Immunotherapy, T-cell activation, thalidomide, adult, aged, anemia, article, cancer chemotherapy, clinical trial, cohort analysis, computer assisted tomography, controlled clinical trial, controlled study, drug efficacy, drug tolerability, dyspnea, evaluation, female, gastrointestinal toxicity, heart arrhythmia, human, hypersensitivity reaction, major clinical study, male, multicenter study, neurotoxicity, neutropenia, phase 1 clinical trial, priority journal, respiratory tract disease, solid tumor, standardization, thorax disease, Antineoplastic Agents, Cohort Studies, Dose-Response Relationship, Drug, Humans, Immunologic Factors, Middle Aged, Neoplasms
DOI: 10.1016/j.ejca.2006.05.018
ISSN: 0959-8049
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2006 Pergamon
Deposited On: 06 Jan 2014 05:25
Last Modified: 31 Jan 2014 05:20

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