Lionel D Lewis, MD, MA, MB-BCH
Professor of Medicine
Director, The Darmouth Clinical Trials Office
Co-DIrector of the NCCC Early Phase Clinical Trials Oncology Group
Vice chair Alliance Pharmacogenetics and Population Pharmacology Committee
Trinity College, Univ of Cambridge, BA 1974
Trinity College, Univ of Cambridge, MA 1978
Univ. of Wales College of Medicine, MB BCh 1977
Univ. of Cambridge MB BChir., 1979
Univ. of Wales College of Medicine, MD 1988
Norris Cotton Cancer Center
Program in Experimental and Molecular Medicine
Section of Clinical Pharmacology
322 West Borwell Building
Dartmouth-Hitchcock Medical Center
Lebanon NH 03756
The clinical pharmacology of antineoplastic agents, particularly the relationship between the pharmacokinetics and pharmacodynamics of these agents in early drug development and proof of principle studies.
Mechanisms of toxicity of nucleoside analogues and antineoplastic agents to the mitochondrion.
Dr. Lewis' work has focused on two areas of research at Dartmouth. He is interested in the Phase I development of antineoplastic agents and established the Phase I Oncology Group at Dartmouth where he has studied a number of anti-cancer agents in early clinical development and defined their pharmacokinetics (PK) and pharmacodynamics (PD) and the PK-PD relationships.
Dr. Lewis has an ongoing interest in drugs which are toxic to the mitochondrion e.g. anti-HIV nucleosides (AZT, ddC and ddI ). Using some of his background in this area he has developed a unique cell line derived from MOLT-4 cells and which are depleted of mtDNA and have impaired mitochondrial function compared to the wild type cell and are useful in elucidating whether the mitochondrion is a target site for xenobiotic toxicity and that the mtDNA depleted MOLT-4 cells (rh0 cells) can be converted to individualized cybrid cells containing mtDNA from humans with abnormalities in mtDNA and studied as a model system for the individual patient.
Rotations and Thesis Projects:
Prior Clinical Pharmacology Fellows in Training have studies drugs causing autophagy in vivo, phase I drug development of an Angiopoietin II inhibitor and a hedgehog pathway inhibitor (smo-antagonist), probe drug studies of CYP450 and effects of novel anti-cancer agents on CYP450 drug metabolism
Co-Investigator Norris Cotton Cancer Center CCSG.
Co-Investigator SYNERGY Dartmouth CTSA (U54)
Geisel II Medical Pharmacology
Geisel IV Medicine/Pharmacology - Clinical Pharmacology & Therapeutics
Dr. Lewis received his B.A. degree from Cambridge University, England in 1974 and received his MB BCh degree from The Welsh National School of Medicine, Cardiff, Wales in 1977. He performed his internship and residency in internal medicine at the University Hospital of Wales at Cardiff and its affiliated hospitals. He then completed his internal medicine training and went on to become an Instructor in Clinical Pharmacology at Guy's Hospital, London from 1982 - 1987. During this time he completed his doctoral thesis (MD, Wales) on the clinical pharmacokinetics of ifosfamide. From 1987-89 he undertook further training and became an accredited specialist in general internal medicine, clinical pharmacology and pulmonology. From 1989-91 he completed a two-year clinical/research fellowship in clinical pharmacology at The Johns Hopkins University Hospital. He then returned to the UK to further obtain experience in Phase I drug studies at the Guys' Drug Research Unit. In 1993 he joined the faculty at Dartmouth Medical School and joined Dr. Nierenberg as the second member of the section of Clinical Pharmacology. This section is active in the areas of basic and translational clinical research, clinical care and consultations, and establishing educational programs for medical students, residents and faculty.
Jennifer A. Kintner, BS, MS
Andrew P Beelen RPh, MD
Anthony Olszanski RPh, MD
Nandi J. Reddy MB. BS
Uday Dandamudi MB.BS
Shodeinde A Coker, MS, MB.BS
Armand R, Channon JY, Kintner J, White KA, Miselis KA, Perez RP, Lewis LD. The effects of ethidium bromide induced loss of mitochondrial DNA on mitochondrial phenotype and ultrastructure in a human leukemia T-cell line (MOLT-4 cells). Toxicol Appl Pharmacol. 2004 Apr;196:68-79. (view details in PubMed)
Yeo T, Kintner J, Armand R, Perez R, Lewis L. Sublethal concentrations of gemcitabine (2',2'-difluorodeoxycytidine) alter mitochondrial ultrastructure and function without reducing mitochondrial DNA content in BxPC-3 human pancreatic carcinoma cells. Hum Exp Toxicol. 2007 Dec;26:911-21. (view details in PubMed)
Curbo S, Johansson M, Balzarini J, Lewis LD, Karlsson A. Acute cytotoxicity of arabinofuranosyl nucleoside analogs is not dependent on mitochondrial DNA. Exp Cell Res. 2009 Sep;315:2539-43. (view details in PubMed)
Lewis NL, Lewis LD, Eder JP, Reddy NJ, Guo F, Pierce KJ, Olszanski AJ, Cohen RB. Phase I study of the safety, tolerability, and pharmacokinetics of oral CP-868,596, a highly specific platelet-derived growth factor receptor tyrosine kinase inhibitor in patients with advanced cancers. J Clin Oncol. 2009 Nov;27:5262-9. (view details in PubMed)
Miller AA, Murry DJ, Owzar K, Hollis DR, Kennedy EB, Abou-Alfa G, Desai A, Hwang J, Villalona-Calero MA, Dees EC, Lewis LD, Fakih MG, Edelman MJ, Millard F, Frank RC, Hohl RJ, Ratain MJ. Phase I and pharmacokinetic study of sorafenib in patients with hepatic or renal dysfunction: CALGB 60301. J Clin Oncol. 2009 Apr;27:1800-5. (view details in PubMed)
Goh BC, Reddy NJ, Dandamudi UB, Laubscher KH, Peckham T, Hodge JP, Suttle AB, Arumugham T, Xu Y, Xu CF, Lager J, Dar MM, Lewis LD. An evaluation of the drug interaction potential of pazopanib, an oral vascular endothelial growth factor receptor tyrosine kinase inhibitor, using a modified Cooperstown 5+1 cocktail in patients with advanced solid tumors. Clin Pharmacol Ther. 2010 Nov;88:652-9. (view details in PubMed)
McGowan MM, Eisenberg BL, Lewis LD, Froehlich HM, Wells WA, Eastman A, Kuemmerle NB, Rosenkrantz KM, Barth RJ, Schwartz GN, Li Z, Tosteson TD, Beaulieu BB, Kinlaw WB. A proof of principle clinical trial to determine whether conjugated linoleic acid modulates the lipogenic pathway in human breast cancer tissue. Breast Cancer Res Treat. 2013 Feb;138:175-83. (view details in PubMed)
Waite A, Balkman C, Bailey D, Kiselow M, Flory A, Beaulieu BB, Lewis LD, McEntee M. Phase II study of oral docetaxel and cyclosporine in canine epithelial cancer. Vet Comp Oncol. 2014 Jun;12:160-8 (view details in PubMed)
Beumer JH, Owzar K, Lewis LD, Jiang C, Holleran JL, Christner SM, Blum W, Devine S, Kolitz JE, Linker C, Vij R, Alyea EP, Larson RA, Ratain MJ, Egorin MJ. Effect of age on the pharmacokinetics of busulfan in patients undergoing hematopoietic cell transplantation; an alliance study (CALGB 10503, 19808, and 100103). Cancer Chemother Pharmacol. 2014 Aug. (view details in PubMed)