Scholars@Duke
David John Adams

David John Adams

Adjunct Associate Professor in the Department of Medicine
Medicine, Medical Oncology
adams041@mc.duke.edu
1700 Ferrell Road, Chapel Hill, NC 27517
1700 Ferrell Road, Chapel Hill, NC 27517

Selected Publications

Phase I Study of the Combination of Bendamustine, Rituximab, and Pixantrone in Patients With Relapsed/Refractory B-cell Non-Hodgkin Lymphoma.

Journal Article Clin Lymphoma Myeloma Leuk · October 2018 BACKGROUND: For patients with aggressive lymphomas who relapse after initial therapy, a durable response is rarely achieved with standard salvage therapies. Significant efforts have focused on the development of novel treatments with reduced toxicity. We c ... Full text Link to item Cite

Dasatinib (BMS-35482) interacts synergistically with docetaxel, gemcitabine, topotecan, and doxorubicin in ovarian cancer cells with high SRC pathway activation and protein expression.

Journal Article Int J Gynecol Cancer · February 2014 PURPOSE: This study aimed to explore the activity of dasatinib in combination with docetaxel, gemcitabine, topotecan, and doxorubicin in ovarian cancer cells. METHODS: Cells with previously determined SRC pathway and protein expression (SRC pathway/SRC pro ... Full text Link to item Cite

Dasatinib (BMS-35482) potentiates the activity of gemcitabine and docetaxel in uterine leiomyosarcoma cell lines.

Journal Article Gynecol Oncol Res Pract · 2014 BACKGROUND: To explore the activity of dasatinib alone and in combination with gemcitabine and docetaxel in uterine leiomyosarcoma (uLMS) cell lines, and determine if dasatinib inhibits the SRC pathway. METHODS: SK-UT-1 and SK-UT-1B uLMS cells were treated ... Full text Open Access Link to item Cite

Abstract 4479: Preclinical toxicology and pharmacology for BACPTDP, a camptothecin that targets hypoxic/acidic tumors.

Conference Cancer Research · April 15, 2013 AbstractBACPTDP is a dipeptide prodrug of the 7-butyl-10-amino analog of camptothecin (BACPT) that is nearing clinical development. BACPTDP was selected based on its ability to exploit the tumor pH gradient ... Full text Cite

The Valley of Death in anticancer drug development: a reassessment.

Journal Article Trends Pharmacol Sci · April 2012 Featured Publication The past decade has seen an explosion in our understanding of cancer biology and with it many new potential disease targets. Nonetheless, our ability to translate these advances into therapies is poor, with a failure rate approaching 90%. Much discussion h ... Full text Link to item Cite

Dasatinib (BMS-35482) has synergistic activity with paclitaxel and carboplatin in ovarian cancer cells.

Journal Article Gynecol Oncol · April 2011 Featured Publication PURPOSE: To explore the activity of dasatinib alone and in combination with paclitaxel and carboplatin in ovarian cancer cells and to determine if dasatinib activity can be predicted based on evaluation of the SRC pathway. EXPERIMENTAL DESIGN: Microarray a ... Full text Link to item Cite

BACPTDP: a water-soluble camptothecin pro-drug with enhanced activity in hypoxic/acidic tumors.

Journal Article Cancer Chemother Pharmacol · April 2011 Featured Publication UNLABELLED: Hypoxia is a common feature of solid tumors. Up-regulation of hypoxia-inducing factor-1 (HIF-1) occurs in the majority of primary malignant tumors and in two-thirds of metastases, while most normal tissues are negative. HIF-1 induces the glycol ... Full text Link to item Cite

Tumor physiology and charge dynamics of anticancer drugs: implications for camptothecin-based drug development.

Journal Article Curr Med Chem · 2011 Featured Publication Charge is an important characteristic of drug molecules, since ionization sites determine the pKa at a particular pH. The pKa in turn can affect many parameters, including solubility, dissolution rate, reaction kinetics, formulation, cell permeability, tis ... Full text Link to item Cite

Phase I evaluation of gemcitabine, mitoxantrone, and their effect on plasma disposition of fludarabine in patients with relapsed or refractory acute myeloid leukemia.

Journal Article Leuk Lymphoma · August 2008 Featured Publication Our aim was to estimate the duration of maximum tolerated dose (MTD) duration for gemcitabine given as a continuous infusion in combination with fludarabine and mitoxantrone and to evaluate potential pharmacokinetic (PK) interactions in 17 patients with re ... Full text Link to item Cite

Anti proliferative activity of ELACY (CP-4055) in combination with cloretazine (VNP40101M), idarubicin, gemcitabine, irinotecan and topotecan in human leukemia and lymphoma cells.

Journal Article Leuk Lymphoma · April 2008 Featured Publication This study evaluated combination drug partners for CP-4055, the C18:1(Delta9,trans) unsaturated fatty acid ester of cytarabine in HL-60 and U937 cells. Growth inhibition was assessed by ATP assay and drug interaction by the combination index and three dime ... Full text Link to item Cite

Antiproliferative Activity of ELACYT™ (CP-4055) in Combination with Cloretazine (VNP40101M), Idarubicin or Gemcitabine in HL-60 Human Myeloid Leukemia Cells.

Conference Blood · November 16, 2006 AbstractCP-4055 (ara-C-5′-elaidic acid ester; ELACYT™) is the C18:1Δ9,trans unsaturated fatty acid ester of cytarabine, a deoxycytidine analog used clinically in the treatment of acute myeloid and lymphoblas ... Full text Cite

Camptothecin analogs with enhanced activity against human breast cancer cells. I. Correlation of potency with lipophilicity and persistence in the cleavage complex.

Journal Article Cancer Chemother Pharmacol · January 2006 Featured Publication The effect of 7-alkyl substitutions on growth inhibition in seven Camptothecin (CPT) ring systems with various groups at the ten position was evaluated in three human breast cancer cell lines that model (1) hormone-sensitive (MCF-7/wt), (2) hormone insensi ... Full text Link to item Cite

Camptothecin analogs with enhanced activity against human breast cancer cells. II. Impact of the tumor pH gradient.

Journal Article Cancer Chemother Pharmacol · January 2006 Featured Publication Human breast tumors often exist in an acidic and hypoxic microenvironment, which can promote resistance to radiation and chemotherapies. A tumor-selective pH gradient arises in these tumors which favors uptake and retention of drugs like camptothecin that ... Full text Link to item Cite

Fixing NIH peer review [3]

Journal Article Scientist · October 10, 2005 Cite

Preclinical evaluation of gemcitabine combination regimens for application in acute myeloid leukemia.

Journal Article Clin Cancer Res · June 1, 2005 The DNA antimetabolite gemcitabine is an anticancer agent with shown preclinical and clinical utility and a low toxicity profile. In this study, we sought to identify and optimize drug partners for binary and tertiary combinations with gemcitabine for use ... Full text Link to item Cite

The impact of tumor physiology on camptothecin-based drug development.

Journal Article Curr Med Chem Anticancer Agents · January 2005 Featured Publication The genomic era has shifted anticancer drug development from its traditional mode concentrated on natural product cytotoxic agents to mechanism-based drug design focused on signal transduction pathways. Yet traditional cytotoxic chemotherapies continue to ... Full text Link to item Cite

The activity of camptothecin analogues is enhanced in histocultures of human tumors and human tumor xenografts by modulation of extracellular pH.

Journal Article Cancer Chemother Pharmacol · September 2003 Featured Publication BACKGROUND: Most solid human tumors exist in an acidic microenvironment, due in part to inefficient vasculature and a higher intrinsic rate of glycolysis. This leads to a tumor-selective pH gradient, which can be exploited therapeutically with antitumor ag ... Full text Link to item Cite

4-hydroperoxycyclophosphamide--purged peripheral blood stem cells for autologous transplantation in patients with acute myeloid leukemia.

Journal Article Biol Blood Marrow Transplant · March 2003 We have performed a phase I dose escalation of 4-Hydroperoxycyclophosphamide (4HC) purging of autologous peripheral blood progenitor cells (PBPCs) to improve the outcome of autologous transplantation for patients with myeloid leukemia. Peripheral blood ste ... Full text Link to item Cite

Phase I evaluation of prolonged-infusion gemcitabine with fludarabine for relapsed or refractory acute myelogenous leukemia.

Journal Article Clin Cancer Res · February 2003 Featured Publication PURPOSE: The purpose of this study was to determine the maximum tolerated duration of infusion of gemcitabine at 10 mg/m(2)/min in combination with fludarabine at 25 mg/m(2) daily for 5 days in the treatment of relapsed or refractory acute myelogenous leuk ... Link to item Cite

IL-4 and interferon gamma regulate expression of inducible nitric oxide synthase in chronic lymphocytic leukemia cells.

Journal Article Leukemia · February 2003 Featured Publication Chronic lymphocytic leukemia (B-CLL) is characterized by the accumulation of long-lived non-dividing CD5(+) B cells. Nitric oxide (NO) is an important regulator of apoptosis, and the viability of cultured B-CLL cells may be dependent on the autocrine produ ... Full text Link to item Cite

Phase I evaluation of prolonged-infusion gemcitabine with irinotecan for relapsed or refractory leukemia or lymphoma.

Journal Article J Clin Oncol · July 1, 2002 Featured Publication PURPOSE: To estimate the maximum-tolerated duration of infusion of gemcitabine at 10 mg/m(2)/min in combination with irinotecan at 40 mg/m(2) daily for 3 days in the treatment of relapsed or refractory acute leukemia or lymphoma. PATIENTS AND METHODS: Pati ... Full text Link to item Cite

Phase I evaluation of prolonged-infusion gemcitabine with mitoxantrone for relapsed or refractory acute leukemia.

Journal Article J Clin Oncol · February 1, 2002 Featured Publication PURPOSE: To ascertain the maximum tolerated duration of infusion of gemcitabine at 10 mg/m(2)/min in combination with mitoxantrone at 12 mg/m(2) daily for 3 days in the treatment of acute leukemia. PATIENTS AND METHODS: Thirty-four patients were enrolled. ... Full text Link to item Cite

Nitric oxide enhancement of fludarabine cytotoxicity for B-CLL lymphocytes.

Journal Article Leukemia · December 2001 Featured Publication Fludarabine is active but not curative in the treatment of chronic lymphocytic leukemia (B-CLL). Nitric oxide (NO) supplied from exogenous, NO-donating pro-drugs can also induce apoptosis and death of acute leukemia cells. This study investigated combinati ... Full text Link to item Cite

Dual role of glutathione in modulating camptothecin activity: depletion potentiates activity, but conjugation enhances the stability of the topoisomerase I-DNA cleavage complex.

Journal Article Mol Cancer Ther · November 2001 Featured Publication Depletion of glutathione (GSH) in MCF-7 and MDA-MB-231 cell lines by pretreatment with the GSH synthesis inhibitor buthionine sulfoximine potentiated the activity of 10,11-methylenedioxy-20(S)-camptothecin, SN-38 [7-ethyl-10-hydroxy-20(S)-camptothecin], to ... Link to item Cite

Cytokine regulation of inducffile nitric oxide synthase (nos2) and nos2 inhibitor-induced apoptosis and death in chronic lymphocytic leukemia cells

Journal Article Blood · December 1, 2000 Chronic lymphocytic leukemia (B-CLL) is a malignancy of a mantle zone-based subpopulation of anergic, self-reactive, activated CD5+ B lymphocytes devoted to the production of polyreactive natural autoantibodies. B-CLL is characterized by the accumulation o ... Cite

Camptothecin analogues with enhanced antitumor activity at acidic pH.

Journal Article Cancer Chemother Pharmacol · 2000 Featured Publication BACKGROUND: Camptothecin (CPT) is a specific inhibitor of the nuclear enzyme topoisomerase I, which is involved in cellular DNA replication and transcription. Topoisomerase I is therefore an attractive target for anticancer drug development, and two analog ... Full text Link to item Cite

Evidence for a role of chloroethylaziridine in the cytotoxicity of cyclophosphamide.

Journal Article Cancer Chemother Pharmacol · 2000 UNLABELLED: A number of investigators have observed that the use of 4-hydroperoxycyclophosphamide (4-HC) in multiwell plate cytotoxicity assays can be associated with toxicity to cells in wells that contain no drug. Previous reports have implicated diffusi ... Full text Link to item Cite

Pre-clinical evaluation of SN-38 and novel camptothecin analogs against human chronic B-cell lymphocytic leukemia lymphocytes.

Journal Article Leuk Res · November 1999 Featured Publication The topoisomerase I inhibitor camptothecin and its analogs have potent activity against a wide range of solid tumors and several hematologic malignancies. Previous studies with these compounds using the MTT metabolic inhibition assay have shown significant ... Full text Link to item Cite

Therapeutic efficacy of vinorelbine against pediatric and adult central nervous system tumors.

Journal Article Cancer Chemother Pharmacol · 1998 PURPOSE: The activity of vinorellbine, a new semisynthetic vinca alkaloid, was evaluated against a battery of human tumor xenografts derived from adult and pediatric CNS malignancies. METHODS: Tumors included adult high-grade gliomas (D-54 MG, D-245 MG), c ... Full text Link to item Cite

Impaired proliferation and tumorigenicity induced by CCAAT/enhancer-binding protein.

Journal Article Cancer Res · March 1, 1996 A plasmid containing the CCAAT/enhancer-binding protein (C/EBP alpha) gene transcriptionally controlled by the metallothionein promoter was constructed. The gene was transfected into the human hepatocellular carcinoma cell lines Hep3B and HepG2. When cultu ... Link to item Cite

P-glycoprotein mediated resistance to 5'-nor-anhydro-vinblastine (Navelbine).

Journal Article Invest New Drugs · 1995 Navelbine (NVB, vinorelbine tartrate) is a semisynthetic Vinca alkaloid in which the catharanthine moiety contains an eight-membered ring in place of the nine-membered ring that is present in all naturally occurring members of the vinblastine group. This m ... Full text Link to item Cite

Antineoplastic drug screening.

Journal Article J Natl Cancer Inst · August 19, 1992 Full text Link to item Cite

An efficient multiple-exposure analysis of the toxicity of crisnatol, a DNA intercalator in phase II clinical trials.

Journal Article Invest New Drugs · April 1992 To investigate the toxicity and mechanism of action of crisnatol (CRS), a new DNA intercalator currently in phase II clinical trials, we analyzed cellular and nuclear flow cytometric (FCM) parameters of murine erythroleukemic cells (MELC) exposed to a rang ... Full text Link to item Cite

Polyploidy induction as a consequence of topoisomerase inhibition. A flow cytometric assessment.

Journal Article Biochem Pharmacol · November 6, 1991 Following recovery from a 4-hr exposure to clinically achievable concentrations of the topoisomerase II inhibitors Adriamycin, teniposide, or amsacrine or the putative topoisomerase II inhibitor crisnatol, murine erythroleukemic cells remained viable for u ... Full text Link to item Cite

Evaluation of arylmethylaminopropanediols by a novel in vitro pharmacodynamic assay: correlation with antitumor activity in vivo.

Journal Article Cancer Res · June 15, 1990 Featured Publication The pharmacodynamics of a new series of antitumor DNA intercalators, known as arylmethylaminopropanediols (AMAPs), has been evaluated in vitro against adherent (MCF-7 human breast cancer) and nonadherent (P388 murine leukemia) cell lines. Previous work had ... Link to item Cite

In vitro pharmacodynamic assay for cancer drug development: application to crisnatol, a new DNA intercalator.

Journal Article Cancer Res · December 1, 1989 Featured Publication A microtiter pharmacodynamic assay is described that evaluates antitumor activity in vitro within a matrix of extracellular drug concentrations (C) and exposure times (T). The results were analyzed according to the pharmacodynamic principle: Cn x T = k, wh ... Link to item Cite

An antibody to the receptor for insulin-like growth factor I inhibits the growth of MCF-7 cells in tissue culture.

Journal Article Biochem Biophys Res Commun · November 30, 1987 Alpha IR-3, a monoclonal antibody to the insulin-like growth factor I receptor which blocks insulin-like growth factor I binding and inhibits its activity, inhibits the binding of 125I-insulin-like growth factor I to MCF-7 cells (an estrogen dependent huma ... Full text Link to item Cite