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Drug Profile

Elacytarabine: lipid vector technology under investigation in acute myeloid leukemia

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Pages 9-24 | Published online: 10 Jan 2014

References

  • Galmarini CM, Mackey JR, Dumontet C. Nucleoside analogues: mechanisms of drug resistance and reversal strategies. Leukemia 15(6), 875–890 (2001).
  • Brueckner B, Rius M, Markelova MR et al. Delivery of 5-azacytidine to human cancer cells by elaidic acid esterification increases therapeutic drug efficacy. Mol. Cancer Ther. 9(5), 1256–1264 (2010).
  • Galmarini CM, Myhren F, Sandvold ML. CP-4055 and CP-4126 are active in ara-C and gemcitabine-resistant lymphoma cell lines. Br. J. Haematol. 144(2), 273–275 (2009).
  • Bergman AM, Kuiper CM, Myhren F, Sandvold ML, Hendriks HR, Peters GJ. Antiproliferative activity and mechanism of action of fatty acid derivatives of arabinosylcytosine (ara-C) in leukemia and solid tumor cell lines. Nucleosides Nucleotides Nucleic Acids 23(8–9), 1523–1526 (2004).
  • Brueckner B, Rius M, Markelova MR et al.. Modulation of cellular uptake and increased therapeutic efficacy of the azacytidine-elaidic acid ester CP-4200 in vitro and in vivo. Cancer Res. 71(8 Suppl.), Abstract 2013 (2011).
  • Bergman AM, Adema AD, Balzarini J et al. Antiproliferative activity, mechanism of action and oral antitumor activity of CP-4126, a fatty acid derivative of gemcitabine, in in vitro and in vivo tumor models. Invest. New Drugs 29(3), 456–466 (2011).
  • Breistøl K, Balzarini J, Sandvold ML et al. Antitumor activity of P-4055 (elaidic acid-cytarabine) compared to cytarabine in metastatic and s.c. human tumor xenograft models. Cancer Res. 59(12), 2944–2949 (1999).
  • Adema A, Smid K, Losekoot N, Myhren F, Sandvold M, Peters G. Fatty acid derivatives of cytarabine and gemcitabine, CP-4055 and CP-4126, show a prolonged cellular retention compared to the parent drug. AACR Annual Meeting. San Diego, CA, USA, 12–16 April 2008 (Abstract 5740).
  • Nilsson B, Hendlisz A, Castella M et al. First-in-human study of a novel nucleoside analogue, CP-4126, in patients with advanced solid tumors. ASCO Meeting Abstracts 27(15S), Abstract 2577 (2009).
  • Adema AD, Smid K, Losekoot N et al. Metabolism and accumulation of the lipophilic deoxynucleoside analogs elacytarabine and CP-4126. Invest. New Drugs 30(5), 1908–1916 (2012).
  • Sandvold ML, Galmarini C, Myhren F, Peters G. The activity of the lipophilic nucleoside derivatives elacytarabine and CP-4126 in a panel of tumor cell lines resistant to nucleoside analogues. Nucleosides Nucleotides Nucleic Acids 29(4-6), 386–393 (2010).
  • Estey EH. General approach to, and perspectives on clinical research in, older patients with newly diagnosed acute myeloid leukemia. Semin. Hematol. 43(2), 89–95 (2006).
  • Thomas X, Dombret H. Timed-sequential chemotherapy as induction and/or consolidation regimen for younger adults with acute myelogenous leukemia. Hematology 12(1), 15–28 (2007).
  • Tsurumi H, Kanemura N, Hara T et al. Therapeutic strategy of untreated de novo acute myeloid leukemia in the elderly: the efficacy of continuous drip infusion with low dose cytarabine and etoposide. J. Cancer Res. Clin. Oncol. 133(8), 547–553 (2007).
  • Cros E, Jordheim L, Dumontet C, Galmarini CM. Problems related to resistance to cytarabine in acute myeloid leukemia. Leuk. Lymphoma 45(6), 1123–1132 (2004).
  • Kufe D, Spriggs D, Egan EM, Munroe D. Relationships among Ara-CTP pools, formation of (Ara-C)DNA, and cytotoxicity of human leukemic cells. Blood 64(1), 54–58 (1984).
  • Estey E, Plunkett W, Dixon D, Keating M, McCredie K, Freireich EJ. Variables predicting response to high dose cytosine arabinoside therapy in patients with refractory acute leukemia. Leukemia 1(8), 580–583 (1987).
  • Cai J, Damaraju VL, Groulx N et al. Two distinct molecular mechanisms underlying cytarabine resistance in human leukemic cells. Cancer Res. 68(7), 2349–2357 (2008).
  • Pastor-Anglada M, Cano-Soldado P, Molina-Arcas M et al. Cell entry and export of nucleoside analogues. Virus Res. 107(2), 151–164 (2005).
  • Weinstein HJ, Griffin TW, Feeney J, Cohen HJ, Propper RD, Sallan SE. Pharmacokinetics of continuous intravenous and subcutaneous infusions of cytosine arabinoside. Blood 59(6), 1351–1353 (1982).
  • Ho DH, Frei E 3rd. Clinical pharmacology of 1-beta-d-arabinofuranosyl cytosine. Clin. Pharmacol. Ther. 12(6), 944–954 (1971).
  • Capizzi RL, Yang JL, Cheng E et al. Alteration of the pharmacokinetics of high-dose ara-C by its metabolite, high ara-U in patients with acute leukemia. J. Clin. Oncol. 1(12), 763–771 (1983).
  • Löwenberg B, Pabst T, Vellenga E et al.; Dutch-Belgian Cooperative Trial Group for Hemato–Oncology (HOVON) and Swiss Group for Clinical Cancer Research (SAKK) Collaborative Group. Cytarabine dose for acute myeloid leukemia. N. Engl. J. Med. 364(11), 1027–1036 (2011).
  • Mayer RJ, Davis RB, Schiffer CA et al. Intensive postremission chemotherapy in adults with acute myeloid leukemia. Cancer and Leukemia Group B. N. Engl. J. Med. 331(14), 896–903 (1994).
  • Bishop JF, Matthews JP, Young GA et al. A randomized study of high-dose cytarabine in induction in acute myeloid leukemia. Blood 87(5), 1710–1717 (1996).
  • Hubeek I, Peters GJ, Broekhuizen R et al. In vitro sensitivity and cross-resistance to deoxynucleoside analogs in childhood acute leukemia. Haematologica 91(1), 17–23 (2006).
  • Lamba JK. Genetic factors influencing cytarabine therapy. Pharmacogenomics 10(10), 1657–1674 (2009).
  • Kufe DW, Major PP, Egan EM, Beardsley GP. Correlation of cytotoxicity with incorporation of ara-C into DNA. J. Biol. Chem. 255(19), 8997–8900 (1980).
  • Grant S. Ara-C: cellular and molecular pharmacology. Adv. Cancer Res. 72, 197–233 (1998).
  • Baker WJ, Royer GL Jr, Weiss RB. Cytarabine and neurologic toxicity. J. Clin. Oncol. 9(4), 679–693 (1991).
  • Mitra AK, Crews KR, Pounds S et al. Genetic variants in cytosolic 5′-nucleotidase II are associated with its expression and cytarabine sensitivity in HapMap cell lines and in patients with acute myeloid leukemia. J. Pharmacol. Exp. Ther. 339(1), 9–23 (2011).
  • Clarke ML, Mackey JR, Baldwin SA, Young JD, Cass CE. The role of membrane transporters in cellular resistance to anticancer nucleoside drugs. Cancer Treat. Res. 112, 27–47 (2002).
  • Takagaki K, Katsuma S, Kaminishi Y et al. Gene-expression profiling reveals down-regulation of equilibrative nucleoside transporter 1 (ENT1) in Ara-C-resistant CCRF-CEM-derived cells. J. Biochem. 136(5), 733–740 (2004).
  • Hubeek I, Stam RW, Peters GJ et al. The human equilibrative nucleoside transporter 1 mediates in vitro cytarabine sensitivity in childhood acute myeloid leukaemia. Br. J. Cancer 93(12), 1388–1394 (2005).
  • Galmarini CM, Thomas X, Calvo F et al. In vivo mechanisms of resistance to cytarabine in acute myeloid leukaemia. Br. J. Haematol. 117(4), 860–868 (2002).
  • Galmarini CM, Thomas X, Calvo F et al. Potential mechanisms of resistance to cytarabine in AML patients. Leuk. Res. 26(7), 621–629 (2002).
  • Gati WP, Paterson AR, Belch AR et al. Es nucleoside transporter content of acute leukemia cells: role in cell sensitivity to cytarabine (araC). Leuk. Lymphoma 32(1–2), 45–54 (1998).
  • Jin G, Matsushita H, Asai S et al. FLT3-ITD induces ara-C resistance in myeloid leukemic cells through the repression of the ENT1 expression. Biochem. Biophys. Res. Commun. 390(3), 1001–1006 (2009).
  • Verhoef V, Sarup J, Fridland A. Identification of the mechanism of activation of 9-β-d-arabinofuranosyladenine in human lymphoid cells using mutants deficient in nucleoside kinases. Cancer Res. 41(11 Pt 1), 4478–4483 (1981).
  • Bhalla K, Nayak R, Grant S. Isolation and characterization of a deoxycytidine kinase-deficient human promyelocytic leukemic cell line highly resistant to 1-β-d-arabinofuranosylcytosine. Cancer Res. 44(11), 5029–5037 (1984).
  • Stegmann AP, Honders WH, Willemze R, Ruiz van Haperen VW, Landegent JE. Transfection of wild-type deoxycytidine kinase (dck) cDNA into an AraC- and DAC-resistant rat leukemic cell line of clonal origin fully restores drug sensitivity. Blood 85(5), 1188–1194 (1995).
  • Abraham A, Varatharajan S, Jayavelu AK et al. Expression of Ara-C metabolizing enzymes mediates in vitro sensitivity to Ara-C in primary AML cells from patients with denovo AML. ASH Annual Meeting Abstracts 118(21), Abstract 3481 (2011).
  • Dumontet C, Fabianowska-Majewska K, Mantincic D et al. Common resistance mechanisms to deoxynucleoside analogues in variants of the human erythroleukaemic line K562. Br. J. Haematol. 106(1), 78–85 (1999).
  • Yamauchi T, Negoro E, Kishi S et al. Intracellular cytarabine triphosphate production correlates to deoxycytidine kinase/cytosolic 5′-nucleotidase II expression ratio in primary acute myeloid leukemia cells. Biochem. Pharmacol. 77(12), 1780–1786 (2009).
  • Galmarini CM. What does over-expression of cN-II enzyme signify in haematological malignancies? Leuk. Res. 31(10),1325–1326 (2007).
  • Galmarini CM, Cros E, Thomas X, Jordheim L, Dumontet C. The prognostic value of cN-II and cN-III enzymes in adult acute myeloid leukemia. Haematologica 90(12), 1699–1701 (2005).
  • Abraham A, Varatharajan S, Abbas S et al. Cytidine deaminase genetic variants influence RNA expression and cytarabine cytotoxicity in acute myeloid leukemia. Pharmacogenomics 13(3), 269–282 (2012).
  • Tang J, Xie X, Zhang X et al. Long term cultured HL-60 cells are intrinsically resistant to Ara-C through high CDA activity. Front. Biosci. 17, 569–574 (2012).
  • Schröder JK, Kirch C, Seeber S, Schütte J. Structural and functional analysis of the cytidine deaminase gene in patients with acute myeloid leukaemia. Br. J. Haematol. 103(4), 1096–1103 (1998).
  • Peters GJ, Voorn DA, Kuiper CM et al. Cell specific cytotoxicity and structure-activity relationship (SAR) of lipophilic 1-B-d-arabinofuranosylcytosine (ARA-C) derivatives. Nucleosides Nucleotides 18(4–5), 877–878 (1998).
  • Wiley JS, Jones SP, Sawyer WH, Paterson AR. Cytosine arabinoside influx and nucleoside transport sites in acute leukemia. J. Clin. Invest. 69(2), 479–489 (1982).
  • Rizzieri D, Vey N, Gobbi M et al. A randomized Phase III study of elacytarabine versus limited investigator’s choice in patients with refractory acute myeloid leukemia (AML). ASCO Meeting Abstracts 29(15 Suppl.), Abstract TPS206 (2011).
  • Rizzieri DA, Vey N, Schlenk RF et al. A Phase II study of elacytarabine/idarubicin as second course remission-induction in patients with acute myeloid leukemia who failed cytarabine/anthracycline, and evaluation of the impact of the nucleoside transporter hENT1 on response. ASH Annual Meeting Abstracts 118(21), Abstract 1533 (2011).
  • Bergman AM, Kuiper CM, Voorn DA et al. Antiproliferative activity and mechanism of action of fatty acid derivatives of arabinofuranosylcytosine in leukemia and solid tumor cell lines. Biochem. Pharmacol. 67(3), 503–511 (2004).
  • Adema AD, Losekoot N, Smid K et al. Induction of resistance to the lipophilic cytarabine prodrug elacytarabine (CP-4055) in CEM leukemic cells. Nucleosides Nucleotides Nucleic Acids 29(4–6), 394–399 (2010).
  • Noordhuis P, Kazemier KM, Kasperrs GJ, Peters GJ. Modulation of metabolism and cytotoxicity of cytosine arabinoside with N-(phosphon)-acetyl-l-aspartate in human leukemic blast cells and cell lines. Leuk. Res. 20(2), 127–134 (1996).
  • Braess J, Voss S, Jahns-Streubel G et al. The pharmacodynamic basis for the increased antileukaemic efficacy of cytosine arabinoside-based treatment regimens in acute myeloid leukaemia with a high proliferative activity. Br. J. Haematol. 110(1), 170–179 (2000).
  • Braess J, Wegendt C, Jahns-Streubel G et al. Successful modulation of high-dose cytosine arabinoside metabolism in acute myeloid leukaemia by haematopoietic growth factors: no effect of ribonucleotide reductase inhibitors fludarabine and gemcitabine. Br. J. Haematol. 109(2), 388–395 (2000).
  • Plunkett W, Gandhi V. Cellular pharmacodynamics of anticancer drugs. Semin. Oncol. 20(1), 50–63 (1993).
  • Adema AD, Laan AC, Myhren F et al. Cell cycle effects of fatty acid derivatives of cytarabine, CP-4055, and of gemcitabine, CP-4126, as basis for the interaction with oxaliplatin and docetaxel. Int. J. Oncol. 36(1), 285–294 (2010).
  • Giles F, Rizzieri D, Ravandi F, Swords R, Jacobsen TF, O’Brien S. Elacytarabine, a novel 5-elaidic acid derivative of cytarabine, and idarubicin combination is active in refractory acute myeloid leukemia. Leuk. Res. 36(4), e71–e73 (2012).
  • Giles FJ, Vey N, Rizzieri D et al. Phase I and pharmacokinetic study of elacytarabine, a novel 5′-elaidic acid derivative of cytarabine, in adults with refractory hematological malignancies. Leukemia 26(7), 1686–1689 (2012).
  • O’Brien S, Kantarjian H, Ravandi F et al. A Phase I dose finding study with CP-4055 (ELACYT) plus idarubicin in patients with relapsed/refractory AML. AACR Meeting Abstracts. Abstract 4589 (2009).
  • Raymond E, Dueland S, Lind MJ et al. Pharmacokinetics of a nucleoside analogue CP-4055 in two Phase I trials using a daily for 5 days schedule and three intermittent weekly or biweekly schedules. AACR Meeting Abstracts 1, Abstract 936 (2005).
  • O’Brien SM, Vey N, Rizzieri DA et al. A Phase I study with CP-4055 in patients with hematologic malignancies. ASCO Meeting Abstracts 26(15 Suppl.), Abstract 2532 (2008).
  • Adams DJ, Sandvold ML, Myhren F, Jacobsen TF, Giles F, Rizzieri DA. Anti proliferative activity of ELACY (CP-4055) in combination with cloretazine (VNP40101M), idarubicin, gemcitabine, irinotecan and topotecan in human leukemia and lymphoma cells. Leuk. Lymphoma 49(4), 786–797 (2008).
  • Bruheim S, Malandsmo GM, Sandvold ML, Myhren F, Fodstad O. Antitumor activity of CP-4055 is enhanced in combination with bevacizumab, cetuximab, and trastuzumab in human NSCLC xenografts. AACR Meeting Abstracts 3, Abstract B287 (2007).
  • O’Brien S, Rizzieri DA, Vey N et al. Elacytarabine has single-agent activity in patients with advanced acute myeloid leukaemia. Br. J. Haematol. 158(5), 581–588 (2012).
  • Rizzieri D, Krug U, Schlenk RF et al. A Phase II study of elacytarabine plus idarubicin as second course remission-induction therapy in patients with acute myeloid leukemia. ASCO Meeting Abstracts 29(15 Suppl.), Abstract TPS207 (2011).
  • Döhner H, Estey EH, Amadori S et al.; European LeukemiaNet. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood 115(3), 453–474 (2010).
  • Roboz GJ. Novel approaches to the treatment of acute myeloid leukemia. Hematology Am. Soc. Hematol. Educ. Program 2011, 43–50 (2011).
  • Yee KW, Keating A. Older patients with acute myeloid leukemia. Expert Rev. Hematol. 3(6), 755–774 (2010).
  • Juliusson G, Antunovic P, Derolf A et al. Age and acute myeloid leukemia: real world data on decision to treat and outcomes from the Swedish Acute Leukemia Registry. Blood 113(18), 4179–4187 (2009).
  • Baz R, Rodriguez C, Fu AZ et al. Impact of remission induction chemotherapy on survival in older adults with acute myeloid leukemia. Cancer 110(8), 1752–1759 (2007).
  • Odenike O, Thirman MJ, Artz AS, Godley LA, Larson RA, Stock W. Gene mutations, epigenetic dysregulation, and personalized therapy in myeloid neoplasia: are we there yet? Semin. Oncol. 38(2), 196–214 (2011).
  • LoRusso PM, Schnipper LE, Stewart DJ, Boerner SA, Averbuch SD, Wolf W. Translating clinical trials into meaningful outcomes. Clin. Cancer Res. 16(24), 5951–5955 (2010).
  • Fojo T, Parkinson DR. Biologically targeted cancer therapy and marginal benefits: are we making too much of too little or are we achieving too little by giving too much? Clin. Cancer Res. 16(24), 5972–5980 (2010).
  • Adema AD, Bijnsdorp IV, Sandvold ML, Verheul HM, Peters GJ. Innovations and opportunities to improve conventional (deoxy)nucleoside and fluoropyrimidine analogs in cancer. Curr. Med. Chem. 16(35), 4632–4643 (2009).

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