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Clinical Pharmacology of Melphalan and Its Implications for Clinical Resistance to Anticancer Agents

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Clinically Relevant Resistance in Cancer Chemotherapy

Part of the book series: Cancer Treatment and Research ((CTAR,volume 112))

Abstract

Melphalan (L-phenylalanine mustard, Alkeran®) was one of the first bifunctional alkylating agents developed for anticancer use. The initial synthesis was reported by Bergel and Stock1. Its design was an outgrowth of studies performed during and following World War II on the mechanisms of mustard gas effects on biological systems. A summary of these early studies by Philips Philips2 is of historical interest; it also serves as a model description of cancer drug development based upon evaluation of molecules observed to have antitumor effects as a result of empiric observation and congener synthesis

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References

  1. Bergel F, Stock JA. Cyto-active amino acid and peptide derivatives: part I: substituted phenylalanines. J Chem Soc, 76:2409–2412, 1954.

    Article  Google Scholar 

  2. Philips FS. Recent contributions to the pharmacology of bis (2-haloethyl) amines and sulfides. Phannacol Rev, 2:281–323, 1950.

    Google Scholar 

  3. Pinguet F, Martel P, Rouanet Pet al.Effect of sodium chloride concentration and temperature on melphalan stability during storage and use. Amer J Hosp Pharm, 51:2701–2704, 1994.

    CAS  Google Scholar 

  4. Pinguet F, Culine S, Bressolle Fet al.A phase I and pharmacokinetic study of melphalan using a 24 hr continuous infusion in patients with advanced malignancies. Clin Cancer Res, 6:57–63, 2000.

    PubMed  CAS  Google Scholar 

  5. Chang SY, Alberts DS, Farquhar D, etal.Hydrolysis and protein binding of melphalan. J Pharmaceut Sci, 67:682–684, 1978.

    Article  CAS  Google Scholar 

  6. Colvin M, Chabner BA. Alkylating agents. In: Cancer Chemotherapy, Principles and Practice, BA Chabner, J Collins (eds.), JB Lippincott, Philadelphia, PA, 276–313, 1990.

    Google Scholar 

  7. Reece PA, Hill HS, Green RMet al.Renal clearance and protein binding of melphalan in patients with cancer. Cancer Chemother Pharmacol, 22:348–352, 1988.

    Article  PubMed  CAS  Google Scholar 

  8. Gera S, Musch E, Osterheld HKOet al.Relevance of the hydrolysis and protein binding of melphalan to the treatment of multiple myeloma. Cancer Chemother Pharmacol, 22:348–352. 1999.

    Google Scholar 

  9. Yu X, Wu Z, Fenselau C. Covalent sequestration of melphalan by metallothionein and selective alkylation of cysteines. Biochem, 34:3377–3385, 1995.

    Article  CAS  Google Scholar 

  10. Ahmed AE, Hsu T-F. Quantitative analysis of melphalan and its major hydrolysate in patients and animals by reversed-phase high-performance liquid chromatography. J Chromatogr, 222:453–460, 1981.

    Article  PubMed  CAS  Google Scholar 

  11. Dulik DM, Fenselau C. Conversion of melphalan to 4-(glutathionyl)phenylalanine. Drug Metab Dispos, 15:195–199, 1987.

    PubMed  CAS  Google Scholar 

  12. Vahrmeijer AL, Snel CAW, Steenvoorden DPTet al.Lack of glutathione conjugation of melphalan in the isolated in situ liver perfusion in humans. Cancer Res, 56:4709–4714, 1996.

    PubMed  CAS  Google Scholar 

  13. Kergueris MF, Milpied N, Moreau Peta/. Pharmacokinetics of high-dose melphalan in adults: influence of renal function. Anticancer Res, 14:2379–2382, 1994.

    PubMed  CAS  Google Scholar 

  14. Tricot G, Alberts DS, Johnson Cet al.Safety of autotransplants with high-dose melphalan in renal failure: a pharmacokinetic and toxicity study. Clin Cancer Res, 2:947–952, 1996.

    PubMed  CAS  Google Scholar 

  15. Alberts DS, Chang SY, Chen HSGet al.Systemic availability of oral melphalan. Cancer Treat Rev, 6:51–55, 1979.

    Article  Google Scholar 

  16. Bosanquet AG, Gilby ED. Comparison of fed and fasted states on the absorption of melphalan in multiple myeloma. Cancer Chemother Pharmacol, 12:183–186, 1984.

    Article  PubMed  CAS  Google Scholar 

  17. Reece PA, Kotasek D, Morris RG, et a/. The effect of food on oral melphalan absorption. Cancer Chemother Pharmacol, 16:194–197, 1986.

    Article  PubMed  CAS  Google Scholar 

  18. Woodhouse KW, Hamilton P, Lennard Aet al.The pharmacokinetics of melphalan in patients with multiple myeloma: an intravenous/oral study using a conventional dose regimen. Eur J Clin Pharmacol, 24:283–285, 1983.

    Article  PubMed  CAS  Google Scholar 

  19. Pallante SL, Fenselau G, Mennel RGet al.Quantitation by gas chromatography-chemical ionization-mass spectrometry of phenylalanine mustard in plasma of patients. Cancer Res, 40:2268–2272, 1980.

    PubMed  CAS  Google Scholar 

  20. Taha ARK, Ahmad RA, Gray Het al.Plasma melphalan and prednisolone concentrations during oral therapy for multiple myeloma. Cancer Chemother Pharmacol, 9:57–60, 2000.

    Article  Google Scholar 

  21. Adair CG, Elnay JC. The effect of dietary amino acids on the gastrointestinal absorption of melphalan and chlorambucil. Cancer Chemother Pharmacol, 19:343–346, 1987.

    Article  PubMed  CAS  Google Scholar 

  22. Reece PA, Dale BM, Morris RGet al.Effect of L-leucine on oral melphalan kinetics in patients. Cancer Chemother Pharmacol, 20:256–258, 1987.

    Article  PubMed  CAS  Google Scholar 

  23. Sviland L, Robinson A, Procter SJet al.Interaction of cimetidine with oral melphalan. A pharmacokinetic study. Cancer Chemother Pharmacol, 20:173–175, 1987.

    Article  PubMed  CAS  Google Scholar 

  24. Choi KE, Ratain MJ, Williams SFet al.Plasma pharmacokinetics of high-dose oral melphalan in patients treated with trialkylator chemotherapy and autologous bone marrow reinfusion. Cancer Res, 49:1318–1321, 1989.

    PubMed  CAS  Google Scholar 

  25. Boros L, Peng YM, Alberts DSet al. Pharmacokinetics of very high-dose oral melphalan in cancer patients. Amer J Clin Oncol, 13:19–22, 1990.

    Article  CAS  Google Scholar 

  26. Alberts DS, Chang SY, Chen H-SGet al.Kinetics of intravenous melphalan. Clin Pharmacol Ther, 26:73–80, 1979.

    PubMed  CAS  Google Scholar 

  27. Gouyette A, Hartmann O, Pico J-L. Pharmacokinetics of high-dose melphalan in children and adults. Cancer Chemother Pharmacol, 16:184–189, 1986.

    Article  PubMed  CAS  Google Scholar 

  28. Ardiet C, Tranchand B, Biron Pet al.Pharmacokinetics of high-dose intravenous melphalan in children and adults with forced diuresis. Cancer Chemother Pharmacol, 16:300–305, 1986.

    Article  PubMed  CAS  Google Scholar 

  29. Peters W, Stuart A, Klotman Met al.High dose combination cyclophosphamide, cisplatin, and melphalan with ABMS: a clinical and pharmacologic study. Cancer Chemother Pharmacol, 23:377–383, 1989.

    Article  PubMed  CAS  Google Scholar 

  30. Moreau P, Kergueris MF, Milpied Net al.A pilot study of 220 mgm2melphalan followed by autologous stem cell transplantation in patients with advanced haematological malignancies: pharmacokinetics and toxicity. Br J Haematol, 95:527–530, 1996.

    Article  PubMed  CAS  Google Scholar 

  31. Pinguet F, Martel P, Fabbro Met al.Pharmacokinetics of high-dose intravenous melphalan in patients undergoing peripheral blood hematopoietic progenitor-cell transplantation. Anticancer Res, 17:605–612, 1997.

    PubMed  CAS  Google Scholar 

  32. Ploin DY, Tranchand B, Guastalla JPet al.Pharmacokinetically guided dosing for intravenous melphalan: a pilot study in patients with advanced ovarian adenocarcinoma. Eur J Cancer, 28A:1311–1315, 1992.

    Article  PubMed  CAS  Google Scholar 

  33. Tranchand B, Ploin DY, Minuit M-Pet al.High-dose melphalan dosage adjustment: possibility of using a test dose. Cancer Chemother Pharmacol, 23:95–100, 1989.

    Article  PubMed  CAS  Google Scholar 

  34. Howell SB, Pfeifle CE, Olshen RA. Intraperitoneal chemotherapy with melphalan. Ann Int Med, 101:14–18, 1984.

    PubMed  CAS  Google Scholar 

  35. Rauschecker HF, Foth F, Michaelis HCet al.Kinetics of melphalan leakage during hyperthermic isolation perfusion in melanoma of the limb. Cancer Chemother Pharmacol, 27:379–384, 2000.

    Article  Google Scholar 

  36. Tranchand B, Ardiet C, Bouffet Eet al.Effect of carboplatin on the pharmacokinetics of melphalan administered intravenously. Bull Cancer (Paris), 81:43–46, 1994.

    CAS  Google Scholar 

  37. Begleiter A, Lam H-YP, Grover Jet al.Evidence for active transport of melphalan by two amino acid carriers in L5178Y lymphoblasts in vitro. Cancer Res, 39:353–359, 1979.

    PubMed  CAS  Google Scholar 

  38. Vistica DT, Toal JN, Rabinowitz M. Amino-acid conferred protection against melphalan: characteristics of melphalan transport and correlation of uptake with cytotoxicity in cultured L1210 leukemia cells. Biochem Pharmacol, 27:2865–2870, 1978.

    Article  PubMed  CAS  Google Scholar 

  39. Goldenberg GJ, Froese EK. Antagonism of the cytocidal activity and uptake of melphalan by tamoxifen in human breast cancer cells in vitro. Biochem Pharmacol, 34:763–770, 1985.

    Article  PubMed  CAS  Google Scholar 

  40. Skipper HE, Aabo K, Bennett LL, Langham WH. Overall tracer studies with 14C-labeled nitrogen mustard in normal and leukemic mice. Cancer, 4:1025–1027, 1951.

    Article  PubMed  CAS  Google Scholar 

  41. Brookes P, Lawley PD. Molecular mechanisms of cytotoxic action of difunctional alkylating agents and resistance to its action. Nature, 206:480–483, 1965.

    Article  PubMed  Google Scholar 

  42. Hoes I, Lemiere F, Van Dongen W, et a/. Analysis of melphalan adducts of 2’- deoxynucleotides in calf thymus DNA hydrolysates by capillary high-performance liquid chromatography-electrospray tandem mass spectrometry. J Chromatogr B Biomed Sci Appl, 736:43–59, 1999.

    Article  PubMed  CAS  Google Scholar 

  43. Povirk LF, Shuker DE. DNA damage and mutagenesis induced by nitrogen mustards. Mutat Res, 318:205–226, 1994.

    Article  PubMed  CAS  Google Scholar 

  44. Ross WE, Ewig RAG, Kohn KW. Differences between melphalan and nitrogen mustard in the formation and removal of DNA crosslinks. Cancer Res, 38:1052–1056, 1978.

    Google Scholar 

  45. Dulik DM, Fenselau C, Hilton J. Characterization of melphalan-glutathione adducts whose formation is catalyzed by glutathione transferases. Biochem Pharmacol, 35:3405–3409,1986.

    Article  PubMed  CAS  Google Scholar 

  46. Dulik DM, Fenselau C. Conversion of melphalan to 4-(glutathionyl)phenylalanine. A novel mechanism for conjugation by glutathione S-transferases. Drug Metab Dispos, 15:195–199, 1987.

    PubMed  CAS  Google Scholar 

  47. Hall AG, Matheson E, Hickson IDet al.Purification of an alpha class glutathione Stransferase from melphalan-resistant Chinese hamster ovary cells and demonstration of its ability to catalyze melphalan-glutathione adduct formation. Cancer Res, 54:3369–3372, 1994.

    PubMed  CAS  Google Scholar 

  48. Vahrmeijer AL, Snel CAW, Steenvoorden DPTet al.Lack of glutathione conjugation of melphalan in the isolated in situ liver perfusion in humans. Cancer Res, 56:4709–4714, 1996.

    PubMed  CAS  Google Scholar 

  49. Hogarth L, English M, Price Let al.The effect of treatment with high dose melphalan, cisplatin or carboplatin on levels of glutathione in plasma, erythrocytes, mononuclear cells and urine. Cancer Chemother Pharmacol, 37:479–485, 1996.

    Article  PubMed  CAS  Google Scholar 

  50. Sarosy G, Leyland-Jones B, Soochan P, Cheson BD. The systemic administration of intravenous melphalan. J Clin Oncol, 6:1768–1782, 1988.

    PubMed  CAS  Google Scholar 

  51. Barlogie B, Jagannath S. Autotransplants in myeloma. Bone Marrow Transplant, 10 Suppl 1:37–44, 1992.

    Google Scholar 

  52. Vesole DH, Barlogie B, Jagannath Set al.High-dose therapy for refractory multiple myeloma: improved prognosis with better supportive care and double transplants. Blood, 84:950–956, 1994.

    PubMed  CAS  Google Scholar 

  53. Pritchard J, McElwain TJ, Graham-Pole J. High-dose melphalan with autologous marrow for treatment of advanced neuroblastoma. Br J Cancer, 45:86–94, 1982.

    Article  PubMed  CAS  Google Scholar 

  54. Maraninchi D, Pico JL, Hartmann Oet al. High-dose melphalan with or without marrow transplantation: a study of dose-effect in patients with refractory and/or relapsed acute leukemias. Cancer Treat Rep, 70:445–448, 1986.

    PubMed  CAS  Google Scholar 

  55. Michel G, Maraninchi D, Demiocq Fet al.Repeated courses of high-dose melphalan and unpurged autologous bone marrow transplantation in children with acutenonlymphoblastic leukemia in first complete remission. Bone Marrow Transpl, 3:105–111, 1988.

    CAS  Google Scholar 

  56. Mills W, Chopra R, McMillan Aet al.BEAM chemotherapy and autologous bone marrow transplantation for patients with relapsed or refractory non-Hodgkin’s lymphoma. J Clin Oncol, 13:588–595, 1995.

    PubMed  CAS  Google Scholar 

  57. Mulder PO, Willemse B, Aalders JGet al.High-dose chemotherapy with autologous bone marrow transplantation in patients with refractory ovarian cancer. Eur J Cancer Clin Oncol, 25, 645–649. 1989.

    Article  PubMed  CAS  Google Scholar 

  58. Stoppa A, Maraninchi D, Viens Pet al.High doses of melphalan and autologous marrow rescue in advanced common epithelial ovarian carcinomas: A retrospective analysis in 35 patients. In: Autologous Bone Marrow Transplantation: Proceedings of the Fourth International Symposium, K Dicke, G Spitzer, A Zander (eds.), 509–515, 1989.

    Google Scholar 

  59. Ayash U, Elias A, Wheeler Cet al.Double dose-intensive chemotherapy with autologous marrow and peripheral progenitor cell support for metastatic breast cancer: a feasibility study. J Clin Oncol, 12:37–44, 1994.

    PubMed  CAS  Google Scholar 

  60. Bitran JD, Samuels B, Klein Let al.Tandem high-dose chemotherapy supported by hematopoietic progenitor cells yields prolonged survival in stage IV breast cancer. Bone Marrow Transplant, 17:157–162, 1996.

    CAS  Google Scholar 

  61. Nieto Y, Xu X, Cagnoni PJet al.Non-predictable pharmacokinetic behavior of cyclophosphamide when combined with high doses of cisplatin and BCNU. Clin Cancer Res, 5:747–751, 1999.

    PubMed  CAS  Google Scholar 

  62. Phillips GL, Hale GA, Howard DSet al.Amifostine (AMJ) cytoprotection (CP) of escalating doses of melphalan (MEL) and autologous hematopoietic stem cell transplantation (AHSCT): a phase I-II study. Proc Amer Soc Clin Oncol, 19:49a, 2000.

    Google Scholar 

  63. Fermand JP, Chevert S, Ravard Pet al.High-dose chemoradiotherapy and autologous blood stem cell transplantation in multiple myeloma: results of a phase II trial involving 63 patients. Blood, 82:2005–2009, 1993.

    PubMed  CAS  Google Scholar 

  64. Ayash L, Elias A, Reich Eet al.Double dose-intensive chemotherapy with autologous marrow and peripheral blood progenitor cell (PBPC) support for metastatic breast cancer (Meeting abstract). Breast Cancer Treat Res, 27:183–183, 1993.

    Google Scholar 

  65. Codling BW, Chakera TM. Pulmonary fibrosis following therapy with melphalan for multiple myeloma. J Clin Pathol, 25:668–673, 1972.

    Article  PubMed  CAS  Google Scholar 

  66. Hartmann O, Oberlin O, Lemerle Jet al.Acute leukemia in two patients with high-dose melphalan and autologous marrow transplantation for malignant solid tumors. J Clin Oncol, 2:1424–1425, 1984.

    PubMed  CAS  Google Scholar 

  67. Govindarajan R, Jagannath S, Flick JTet al.Preceding standard therapy is the likely cause of MDS after autotransplants for multiple myeloma. Br J Hemat, 95:349–356, 1996.

    Article  CAS  Google Scholar 

  68. Teicher BA, Holden SA, al Achi A, Herman TS. Classification of antineoplastic treatments by their differential toxicity toward putative oxygenated and hypoxic tumor subpopulations in vivo in the FSaIIC murine fibrosarcoma. Cancer Res, 50:3339–3344, 1990.

    PubMed  CAS  Google Scholar 

  69. Skarsgard LD, Skwarchuk MW, Vinczan Aet al.The cytotoxicity of melphalan and its relationship to pH, hypoxia and drug uptake. Anticancer Res, 15:219–223, 1995.

    PubMed  CAS  Google Scholar 

  70. Sheikh MS, Antinore MJ, Huang Y, Pomace Al Jr. Ultraviolet-irradiation-induced apoptosis is mediated via ligand independent activation of tumor necrosis factor receptor 1. Oncogene, 17:2555–2563, 1998.

    Article  PubMed  CAS  Google Scholar 

  71. Hantel A, Ayala S. Mechanisms contributing to melphalan (M) resistance (Mr) in human colon cancer cell lines (Heed). Proc Amer Assoc Cancer Res, 32:A2127, 1991.

    Google Scholar 

  72. Uanivee B, Averiul DA. Melphalan resistance and photoaffinity labelling of Pglycoprotein in multidrug-resistant Chinese hamster ovary cells: reversal of resistance by cyclosporin A and hyperthermia. Biochem Pharmacol, 58:291–302, 1999.

    Article  Google Scholar 

  73. Hansson J, Berhane K, Castro VMet al.Sensitization of human melanoma cells to the cytotoxic effect of melphalan by the glutathione transferase inhibitor ethacrynic acid. Cancer Res, 51:94–98, 1991.

    PubMed  CAS  Google Scholar 

  74. Gupta V, Jani JP, Jacobs Set al.Activity of melphalan in combination with the glutathione transferase inhibitor sulfasalazine. Cancer Chemother Pharmacol, 36:13–19, 1995.

    Article  PubMed  CAS  Google Scholar 

  75. Jungnelius U, Hao XY, Skog Set al.Cell cycle dependent sensitivity of human melanoma cells to melphalan is correlated with the activity and cellular concentration of glutathione transferases. Carcinogenesis, 15:99–103, 1994.

    Article  PubMed  CAS  Google Scholar 

  76. Geleziunas R, McQuillan A, Malapetsa Aet al.Increased DNA synthesis and repair-enzyme expression in lymphocytes from patients with chronic lymphocytic leukemia resistant to nitrogen mustards. J Natl Cancer Inst, 83:557–564, 1991.

    Article  PubMed  CAS  Google Scholar 

  77. Brown JM, Wouters BG. Apoptosis, p53, and tumor cell sensitivity to anticancer agents.Cancer Res, 59:1391–1399, 1999.

    PubMed  CAS  Google Scholar 

  78. Batist G, Torres-Garcia S, Demuys JMet al.Enhanced DNA cross-link removal: the apparent mechanism of resistance in a clinically relevant melphalan-resistant human breast cancer cell line. Mol Pharmacol, 36:224–230, 1989.

    PubMed  CAS  Google Scholar 

  79. Teicher BA, Ara G, Keyes SRet al.Acute in vivo resistance in high-dose therapy. Clin Cancer Res, 4:483–491, 1998.

    CAS  Google Scholar 

  80. Holden SA, Teicher BA, Ayash Uet al.A preclinical model for sequential high-dose chemotherapy. Cancer Chemother Pharmacol, 36:61–64, 1995.

    Article  PubMed  CAS  Google Scholar 

  81. Bubley GJ, Ogata GK, Dupuis NP, Teicher BA. Detection of sequence-specific antitumor alkylating agent DNA damage from cells treated in culture and from a patient. Cancer Res, 54:6325–6329, 1994.

    PubMed  CAS  Google Scholar 

  82. Frei E III, Ara G, Teicher Bet al.Double high-dose chemotherapy with stem cell rescue (HD-SCR) in patients with breast cancer - effect of sequence. Cancer Chemother Pharmacol, 45:239–246, 2000.

    Article  PubMed  CAS  Google Scholar 

  83. Fisher B, Anderson S, Wickerham DLet a/. Increased intensification and total dose of cyclophosphamide in a doxorubicin-cyclophosphamide regimen for the treatment of primary breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-22. J Clin Oncol, 15:1858–1869, 1997.

    PubMed  CAS  Google Scholar 

  84. Fisher B, Anderson S, DeCillis Aet al.Further evaluation of intensified and increased total dose of cyclophosphamide for the treatment of primary breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-25. J Clin Oncol, 17:3374–3388, 1999.

    PubMed  CAS  Google Scholar 

  85. Zuazu I, Brunet S, Fernandez MT, Domingo-Albos A. Hepatic veno-occlusive disease in a patient undergoing bone marrow autotransplant after busulfan and melphalan conditioning (letter). Med Clin (Bare), 94:119, 1990.

    Google Scholar 

  86. Phillips GU, Shepherd JD, Barnett MJet al.Busulfan, cyclophosphamide, and melphalan conditioning for autologous bone marrow transplantation in hematologic malignancy. J Clin Oncol, 9:1880–1888, 1991.

    PubMed  CAS  Google Scholar 

  87. Peters W, Stuart A, Klotman Met al.High dose combination cyclophosphamide, cisplatin, and melphalan with ABMS: a clinical and pharmacologic study. Cancer Chemother Pharmacol, 23:377–383, 1989.

    Article  PubMed  CAS  Google Scholar 

  88. Martino R, Badell I, Brunet Set al.High-dose busulfan and melphalan before bone marrow transplantation for acute nonlymphoblastic leukemia. Bone Marrow Transplant, 16:209–212, 1995.

    PubMed  CAS  Google Scholar 

  89. Bensinger WI, Schiffman KS, Holmberg Uet al.High-dose busulfan, melphalan, thiotepa and peripheral blood stem cell infusion for the treatment of metastatic breast cancer. Bone Marrow Transplant, 19:1183–1189, 1997.

    Article  PubMed  CAS  Google Scholar 

  90. Gandola U, Lombardi F, Siena Set al.Total body irradiation and high-dose melphalan with bone marrow transplantation at Istituto Nazionale Tumori, Milan, Italy. Radiother Oncol, 18 Suppl 1:105–109, 1990.

    Article  Google Scholar 

  91. Keating A, Crump M. High dose etoposide, melphalan, total body irradiation and ABMT for acute myeloid leukemia in first remission. Leukemia, 6 Suppl 4:90–91, 1992.

    Google Scholar 

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  1. Bone Marrow Transplant Program, University of Colorado Health Science Center, Denver, Colorado, USA

    Roy B. Jones

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  1. MD Anderson Cancer Center, Houston, Texas, USA

    Borje Andersson M.D., Ph.D

  2. Cross Cancer Institute, Edmonton, Alberta, Canada

    David Murray Ph.D

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Jones, R.B. (2002). Clinical Pharmacology of Melphalan and Its Implications for Clinical Resistance to Anticancer Agents. In: Andersson, B., Murray, D. (eds) Clinically Relevant Resistance in Cancer Chemotherapy. Cancer Treatment and Research, vol 112. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1173-1_15

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