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 Etoposide Phosphate

etoposide phosphate is a phosphate salt of a semisynthetic derivative of podophyllotoxin. Etoposide binds to the enzyme topoisomerase II, inducing double-strand DNA breaks, inhibiting DNA repair, and resulting in decreased DNA synthesis and tumor cell proliferation. Cells in the S and G2 phases of the cell cycle are most sensitive to this agent. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus)

According to http://en.wikipedia.org/wiki/Etoposide, Etoposide phosphate (brand names: Eposin, Etopophos, Vepesid, VP-16) is a cancer drug. It inhibits the enzyme topoisomerase II, which unwinds DNA, and by doing so causes DNA strands to break. Cancer cells are less able to repair this damage than healthy cells. It is used as a form of chemotherapy for cancers such as Ewing's sarcoma, lung cancer, testicular cancer, lymphoma, non-lymphocytic leukemia, and glioblastoma multiforme. It is often given in combination with other drugs. It is also sometimes used in a conditioning regimen prior to a bone marrow or blood stem cell transplant. Its chemical make-up derives from podophyllotoxin, a toxin found in the American Mayapple. The name "VP-16"likely comes from a compounding of the last name of the chemists who performed early work on the drug (von Wartburg and von Kuhn) and podophyllotoxin[1]. Another chemist who was integral in the development of podophyllotoxin-based chemotherapeutics was Hartmann F. Stähelin.

DRUG DESCRIPTION

ETOPOPHOS (etoposide phosphate) for Injection is an antineoplastic agent which is available for intravenous infusion as a sterile lyophile in single-dose vials containing etoposide phosphate equivalent to 100 mg etoposide, 32.7 mg sodium citrate USP, and 300 mg dextran 40. Etoposide phosphate is a water soluble ester of etoposide (commonly known as VP-16), a semi-synthetic derivative of podophyllotoxin. The water solubility of etoposide phosphate lessens the potential for precipitation following dilution and during intravenous administration.

  1: Guillaume DJ, Doolittle ND, Gahramanov S, Hedrick NA, Delashaw JB, Neuwelt EA. Intra-arterial chemotherapy with osmotic blood-brain barrier disruption for aggressive oligodendroglial tumors: results of a phase I study. Neurosurgery. 2010 Jan;66(1):48-58; discussion 58. PubMed PMID: 20023537; PubMed Central PMCID: PMC2806091.

2: Lata H, Mizuno CS, Moraes RM. The role of biotechnology in the production of the anticancer compound podophyllotoxin. Methods Mol Biol. 2009;547:387-402. PubMed PMID: 19521861.

3: Xu H, Lv M, Tian X. A review on hemisynthesis, biosynthesis, biological activities, mode of action, and structure-activity relationship of podophyllotoxins: 2003-2007. Curr Med Chem. 2009;16(3):327-49. Review. PubMed PMID: 19149581.

4: Macnealy MW, Newton HB, McGregor JM, Bell SD, Ray Chaudhury A, Slone HW, Bourekas EC. Primary meningeal CNS lymphoma treated with intra-arterial chemotherapy and blood-brain barrier disruption. J Neurooncol. 2008 Dec;90(3):329-33. Epub 2008 Aug 30. PubMed PMID: 18758913.

5: Lamblin F, Hano C, Fliniaux O, Mesnard F, Fliniaux MA, Lainé E. [Interest of lignans in prevention and treatment of cancers]. Med Sci (Paris). 2008 May;24(5):511-9. Review. French. PubMed PMID: 18466729.

6: Collier K, Schink C, Young AM, How K, Seckl M, Savage P. Successful treatment

with etoposide phosphate in patients with previous etoposide hypersensitivity. J

Oncol Pharm Pract. 2008 Mar;14(1):51-5. PubMed PMID: 18337441.

7: Polycarpou-Schwarz M, Müller K, Denger S, Riddell A, Lewis J, Gannon F, Reid G. Thanatop: a novel 5-nitrofuran that is a highly active, cell-permeable inhibitor of topoisomerase II. Cancer Res. 2007 May 1;67(9):4451-8. PubMed PMID:

17483360.

8: Leger DY, Liagre B, Beneytout JL. Low dose leflunomide activates PI3K/Akt signalling in erythroleukemia cells and reduces apoptosis induced by anticancer agents. Apoptosis. 2006 Oct;11(10):1747-60. PubMed PMID: 16927021.

9: Reck M, von Pawel J, Macha HN, Kaukel E, Deppermann KM, Bonnet R, Ulm K, Hessler S, Gatzemeier U. Efficient palliation in patients with small-cell lung cancer by a combination of paclitaxel, etoposide and carboplatin: quality of life and 6-years'-follow-up results from a randomised phase III trial. Lung Cancer. 2006 Jul;53(1):67-75. Epub 2006 May 19. PubMed PMID: 16713013.

10: Hartmann JT, Lipp HP. Camptothecin and podophyllotoxin derivatives: inhibitors of topoisomerase I and II - mechanisms of action, pharmacokinetics and toxicity profile. Drug Saf. 2006;29(3):209-30. Review. PubMed PMID: 16524321.

11: Demirci H, Shields CL, Meadows AT, Shields JA. Long-term visual outcome following chemoreduction for retinoblastoma. Arch Ophthalmol. 2005 Nov;123(11):1525-30. PubMed PMID: 16286614.

12: Greco FA, Thompson DS, Morrissey LH, Erland JB, Burris HA 3rd, Spigel DR, Joseph G, Corso SW, Spremulli E, Hainsworth JD. Paclitaxel/carboplatin/etoposide

versus paclitaxel/topotecan for extensive-stage small cell lung cancer: a Minnie

Pearl Cancer Research Network randomized, prospective phase II trial. Oncologist. 2005 Oct;10(9):728-33. PubMed PMID: 16249353.

13: Abel E, Ekman T, Warnhammar E, Hultborn R, Jennische E, Lange S. Early disturbance of microvascular function precedes chemotherapy-induced intestinal injury. Dig Dis Sci. 2005 Sep;50(9):1729-33. PubMed PMID: 16133980.

14: Papadopoulos KP, Noguera-Irizarry W, Wiebe L, Hesdorffer CS, Garvin J, Nichols GL, Vahdat LH, Lo KM, Skerrett D, Bernstein D, Sharpe E, Savage DG. Pilot study of tandem high-dose chemotherapy and autologous stem cell transplantation with a novel combination of regimens in patients with poor risk lymphoma. Bone Marrow Transplant. 2005 Sep;36(6):491-7. PubMed PMID: 16044139.

15: Levitt NC, Propper DJ, Madhusudan S, Braybrooke JP, Echeta C, Te Poele R, Davies SL, Flanagan E, Hickson ID, Joel S, Ganesan TS. Pharmacokinetically guided phase I trial of topotecan and etoposide phosphate in recurrent ovarian cancer. Br J Cancer. 2005 Jul 11;93(1):60-9. PubMed PMID: 15956976; PubMed Central PMCID: PMC2361471.

16: You Y. Podophyllotoxin derivatives: current synthetic approaches for new anticancer agents. Curr Pharm Des. 2005;11(13):1695-717. Review. PubMed PMID: 15892669.

17: Belinsky MG, Dawson PA, Shchaveleva I, Bain LJ, Wang R, Ling V, Chen ZS, Grinberg A, Westphal H, Klein-Szanto A, Lerro A, Kruh GD. Analysis of the in vivo functions of Mrp3. Mol Pharmacol. 2005 Jul;68(1):160-8. Epub 2005 Apr 6. PubMed PMID: 15814571.

18: Marigny K, Aubin F, Burgot G, Le Gall E, Gandemer V. Particular cutaneous side effects with etoposide-containing courses: is VP16 or etoposide phosphate responsible? Cancer Chemother Pharmacol. 2005 Mar;55(3):244-50. Epub 2004 Nov 4.

PubMed PMID: 15526203.

19: Gordaliza M, García PA, del Corral JM, Castro MA, Gómez-Zurita MA. Podophyllotoxin: distribution, sources, applications and new cytotoxic derivatives. Toxicon. 2004 Sep 15;44(4):441-59. Review. PubMed PMID: 15302526.

20: Ragozina NY, Pütz M, Heissler S, Faubel W, Pyell U. Quantification of etoposide and etoposide phosphate in human plasma by micellar electrokinetic chromatography and near-field thermal lens detection. Anal Chem. 2004 Jul 1;76(13):3804-9. PubMed PMID: 15228358.

21: Kruczynski A, Barret JM, Van Hille B, Chansard N, Astruc J, Menon Y, Duchier

C, Créancier L, Hill BT. Decreased nucleotide excision repair activity and alterations of topoisomerase IIalpha are associated with the in vivo resistance of a P388 leukemia subline to F11782, a novel catalytic inhibitor of topoisomerases I and II. Clin Cancer Res. 2004 May 1;10(9):3156-68. PubMed PMID:

15131057.

22: Neuwelt EA, Pagel MA, Kraemer DF, Peterson DR, Muldoon LL. Bone marrow chemoprotection without compromise of chemotherapy efficacy in a rat brain tumor

model. J Pharmacol Exp Ther. 2004 May;309(2):594-9. Epub 2004 Jan 29. PubMed PMID: 14752063.

23: Braybrooke JP, Levitt NC, Joel S, Davis T, Madhusudan S, Turley H, Wilner S,

Harris AL, Talbot DC. Pharmacokinetic study of cisplatin and infusional etoposide phosphate in advanced breast cancer with correlation of response to topoisomerase IIalpha expression. Clin Cancer Res. 2003 Oct 15;9(13):4682-8. PubMed PMID: 14581337.

24: Kim KY, Cho YJ, Jeon GA, Ryu PD, Myeong JN. Membrane-bound alkaline phosphatase gene induces antitumor effect by G2/M arrest in etoposide phosphate-treated cancer cells. Mol Cell Biochem. 2003 Oct;252(1-2):213-21. PubMed PMID: 14577595.

25: Demirci H, Eagle RC Jr, Shields CL, Shields JA. Histopathologic findings in eyes with retinoblastoma treated only with chemoreduction. Arch Ophthalmol. 2003

Aug;121(8):1125-31. PubMed PMID: 12912690.

26: Tyson RM, Siegal T, Doolittle ND, Lacy C, Kraemer DF, Neutwelt EA. Current status and future of relapsed primary central nervous system lymphoma (PCNSL). Leuk Lymphoma. 2003 Apr;44(4):627-33. PubMed PMID: 12769339.

27: Dorr RT, Briggs A, Kintzel P, Meyers R, Chow HH, List A. Comparative pharmacokinetic study of high-dose etoposide and etoposide phosphate in patients

with lymphoid malignancy receiving autologous stem cell transplantation. Bone Marrow Transplant. 2003 Apr;31(8):643-9. PubMed PMID: 12692603.

28: Demperio VL. Determination of etoposide phosphate intermediates by gradient liquid chromatography using postcolumn derivatization with cuprammonium hydroxide. J Chromatogr A. 2002 Apr 5;952(1-2):283-7. PubMed PMID: 12064540.

29: Hayes GM, Carpenito C, Davis PD, Dougherty ST, Dirks JF, Dougherty GJ. Alternative splicing as a novel of means of regulating the expression of therapeutic genes. Cancer Gene Ther. 2002 Feb;9(2):133-41. PubMed PMID: 11857030.

30: Siderov J, Prasad P, De Boer R, Desai J. Safe administration of etoposide phosphate after hypersensitivity reaction to intravenous etoposide. Br J Cancer.

2002 Jan 7;86(1):12-3. PubMed PMID: 11857004; PubMed Central PMCID: PMC2746527.

31: Neuwelt EA, Pagel MA, Hasler BP, Deloughery TG, Muldoon LL. Therapeutic efficacy of aortic administration of N-acetylcysteine as a chemoprotectant against bone marrow toxicity after intracarotid administration of alkylators, with or without glutathione depletion in a rat model. Cancer Res. 2001 Nov 1;61(21):7868-74. PubMed PMID: 11691805.

32: Shields CL, Meadows AT, Shields JA, Carvalho C, Smith AF. Chemoreduction for

retinoblastoma may prevent intracranial neuroblastic malignancy (trilateral retinoblastoma). Arch Ophthalmol. 2001 Sep;119(9):1269-72. PubMed PMID: 11545631.

33: Reif S, Kingreen D, Kloft C, Grimm J, Siegert W, Schunack W, Jaehde U. Bioequivalence investigation of high-dose etoposide and etoposide phosphate in lymphoma patients. Cancer Chemother Pharmacol. 2001 Aug;48(2):134-40. PubMed PMID: 11561779.

34: Quoix E, Breton JL, Daniel C, Jacoulet P, Debieuvre D, Paillot N, Kessler R,

Moreau L, Coëtmeur D, Lemarié E, Milleron B. Etoposide phosphate with carboplatin in the treatment of elderly patients with small-cell lung cancer: a phase II study. Ann Oncol. 2001 Jul;12(7):957-62. PubMed PMID: 11521802.

35: Kingreen D, Beyer J, Kleiner S, Reif S, Huhn D, Siegert W. ICE--an efficient

drug combination for stem cell mobilization and high-dose treatment of malignant

lymphoma. Eur J Haematol Suppl. 2001 Jul;64:46-50. PubMed PMID: 11486402.

36: Soetebeer UB, Schierenberg MO, Schulz H, Hempel G, Andresen P, Blaschke G. Simultaneous quantification of etoposide and etoposide phosphate in human plasma

by capillary electrophoresis using laser-induced native fluorescence detection. Anal Chem. 2001 May 15;73(10):2178-82. PubMed PMID: 11393838.

37: Osztie E, Várallyay P, Doolittle ND, Lacy C, Jones G, Nickolson HS, Neuwelt EA. Combined intraarterial carboplatin, intraarterial etoposide phosphate, and IV Cytoxan chemotherapy for progressive optic-hypothalamic gliomas in young children. AJNR Am J Neuroradiol. 2001 May;22(5):818-23. PubMed PMID: 11337321.

38: Yuan P, Grimes GJ, Shankman SE, Daniels CE, Goldspiel BR, Potti GK. Compatibility and stability of vincristine sulfate, doxorubicin hydrochloride, and etoposide phosphate in 0.9% sodium chloride injection. Am J Health Syst Pharm. 2001 Apr 1;58(7):594-8. PubMed PMID: 11296609.

39: Junghanss C, Leithäuser M, Wilhelm S, Kleine HD, Knopp A, Decker S, Alscher A, Casper J, Köhne CH, Freund M. High-dose etoposide phosphate and G-CSF mobilizes peripheral blood stem cells in patients that previously failed to mobilize. Ann Hematol. 2001 Feb;80(2):96-102. PubMed PMID: 11261332.

40: Fortin D, McCormick CI, Remsen LG, Nixon R, Neuwelt EA. Unexpected neurotoxicity of etoposide phosphate administered in combination with other chemotherapeutic agents after blood-brain barrier modification to enhance delivery, using propofol for general anesthesia, in a rat model. Neurosurgery. 2000 Jul;47(1):199-207. PubMed PMID: 10917363.

41: Canel C, Moraes RM, Dayan FE, Ferreira D. Podophyllotoxin. Phytochemistry. 2000 May;54(2):115-20. Review. PubMed PMID: 10872202.

42: Benz MS, Scott IU, Murray TG, Kramer D, Toledano S. Complications of systemic chemotherapy as treatment of retinoblastoma. Arch Ophthalmol. 2000 Apr;118(4):577-8. PubMed PMID: 10766148.

43: Fortin D, McAllister LD, Nesbit G, Doolittle ND, Miner M, Hanson EJ, Neuwelt

EA. Unusual cervical spinal cord toxicity associated with intra-arterial carboplatin, intra-arterial or intravenous etoposide phosphate, and intravenous cyclophosphamide in conjunction with osmotic blood brain-barrier disruption in the vertebral artery. AJNR Am J Neuroradiol. 1999 Nov-Dec;20(10):1794-802. PubMed PMID: 10588099.

44: Morlet N, Stayt J, Vaegan, Salonikas C, Naidoo D, Crouch R, Graham G, Coroneo M. Etoposide as a virocidal anticytomegalovirus therapy: intravitreal toxicology

and pharmacology in rabbits. Aust N Z J Ophthalmol. 1999 Oct;27(5):342-9. PubMed

PMID: 10571395.

45: Bernstein BJ, Troner MB. Successful rechallenge with etoposide phosphate after an acute hypersensitivity reaction to etoposide. Pharmacotherapy. 1999 Aug;19(8):989-91. PubMed PMID: 10453971.

46: Etoposide phosphate: new preparation. Makes outpatient therapy easier. Prescrire Int. 1998 Jun;7(35):75-6. PubMed PMID: 10342922.

47: Zhang Y, Trissel LA. Physical and chemical stability of etoposide phosphate solutions. J Am Pharm Assoc (Wash). 1999 Mar-Apr;39(2):146-50. PubMed PMID: 10079650.

48: Trissel LA, Martinez JF, Simmons M. Compatibility of etoposide phosphate with selected drugs during simulated Y-site injection. J Am Pharm Assoc (Wash). 1999 Mar-Apr;39(2):141-5. PubMed PMID: 10079649.

49: Lauer AK, Wobig JL, Shults WT, Neuwelt EA, Wilson MW. Severe ocular and orbital toxicity after intracarotid etoposide phosphate and carboplatin therapy.

Am J Ophthalmol. 1999 Feb;127(2):230-3. PubMed PMID: 10030580.

50: Hande KR. Etoposide: four decades of development of a topoisomerase II inhibitor. Eur J Cancer. 1998 Sep;34(10):1514-21. Review. PubMed PMID: 9893622.

51: Mrestani Y, Neubert R. Separation of etoposide phosphate and methotrexate by

capillary zone electrophoresis using UV detection with a high sensitivity cell. Electrophoresis. 1998 Nov;19(16-17):3022-5. PubMed PMID: 9870407.

52: Joel S, O'Byrne K, Penson R, Papamichael D, Higgins A, Robertshaw H, Rudd R,

Talbot D, Slevin M. A randomised, concentration-controlled, comparison of standard (5-day) vs. prolonged (15-day) infusions of etoposide phosphate in small-cell lung cancer. Ann Oncol. 1998 Nov;9(11):1205-11. PubMed PMID: 9862051.

53: Wijnholds J, Scheffer GL, van der Valk M, van der Valk P, Beijnen JH, Scheper RJ, Borst P. Multidrug resistance protein 1 protects the oropharyngeal mucosal layer and the testicular tubules against drug-induced damage. J Exp Med. 1998 Sep 7;188(5):797-808. PubMed PMID: 9730882; PubMed Central PMCID: PMC2213389.

54: Kleta R, Wagner A, Jürgens H. Recurrence of SIADH after a high-dose regimen of thiotepa, carboplatin, and etoposide phosphate. Med Pediatr Oncol. 1998 Aug;31(2):129. PubMed PMID: 9680945.

55: Gündüz K, Shields JA, Eagle RC Jr, Shields CL, De Potter P, Klombers L. Malignant rhabdoid tumor of the orbit. Arch Ophthalmol. 1998 Feb;116(2):243-6. Review. PubMed PMID: 9488282.

56: Kerr DE, Wu GY, Wu CH, Senter PD. Listeriolysin O potentiates immunotoxin and bleomycin cytotoxicity. Bioconjug Chem. 1997 Nov-Dec;8(6):781-4. PubMed PMID: 9404648.

57: Lorico A, Rappa G, Finch RA, Yang D, Flavell RA, Sartorelli AC. Disruption of the murine MRP (multidrug resistance protein) gene leads to increased sensitivity to etoposide (VP-16) and increased levels of glutathione. Cancer Res. 1997 Dec 1;57(23):5238-42. PubMed PMID: 9393741.

58: Soni N, Meropol NJ, Pendyala L, Noel D, Schacter LP, Gunton KE, Creaven PJ. Phase I and pharmacokinetic study of etoposide phosphate by protracted venous infusion in patients with advanced cancer. J Clin Oncol. 1997 Feb;15(2):766-72. PubMed PMID: 9053503.

59: Hainsworth JD, Utley SM, Greco FA. Phase I study of high dose etoposide phosphatase with filgrastim (G-CSF) in the treatment of advanced refractory malignancies. Invest New Drugs. 1997;15(4):325-9. PubMed PMID: 9547675.

60: de Jong RS, Slijfer EA, Uges DR, Mulder NH, de Vries EG. Conversion of the prodrug etoposide phosphate to etoposide in gastric juice and bile. Br J Cancer.

1997;76(11):1480-3. PubMed PMID: 9400945; PubMed Central PMCID: PMC2228182.

61: de Jong RS, Mulder NH, Uges DR, Kaul S, Winograd B, Sleijfer DTh, Groen HJ, Willemse PH, van der Graaf WT, de Vries EG. Randomized comparison of etoposide pharmacokinetics after oral etoposide phosphate and oral etoposide. Br J Cancer.

1997;75(11):1660-6. PubMed PMID: 9184183; PubMed Central PMCID: PMC2223531.

62: Lowis SP, Newell DR. Etoposide for the treatment of paediatric tumours: what

is the best way to give it? Eur J Cancer. 1996 Dec;32A(13):2291-7. Review. PubMed PMID: 9038612.

63: Sarah Cannon Cancer Center Consensus Conference on Novel Developments with Podophyllotoxin Therapy. Semin Oncol. 1996 Dec;23(6 Suppl 13):1-60. Review. PubMed PMID: 9011942.

64: Doyle JJ, Dezii CM, Sadana A. A pharmacoeconomic evaluation of cisplatin in combination with either etoposide or etoposide phosphate in small cell lung cancer. Semin Oncol. 1996 Dec;23(6 Suppl 13):51-60. PubMed PMID: 8996576.

65: Greco FA, Hainsworth JD. Clinical studies with etoposide phosphate. Semin Oncol. 1996 Dec;23(6 Suppl 13):45-50. PubMed PMID: 8996575.

66: Porter D, Boddy A, Thomas H, Lind M, Newell D, Calvert AH, Robson L, Brampton M, Abrahamsen D, Winograd B. Etoposide phosphate infusion with therapeutic drug monitoring in combination with carboplatin dosed by area under the curve: a cancer research campaign phase I/II committee study. Semin Oncol. 1996 Dec;23(6 Suppl 13):34-44. PubMed PMID: 8996574.

67: Brooks DJ, Alberts DS. A phase I study of etoposide phosphate plus paclitaxel. Semin Oncol. 1996 Dec;23(6 Suppl 13):30-3. PubMed PMID: 8996573.

68: Kaul S, Srinivas NR, Mummaneni V, Igwemezie LN, Barbhaiya RH. Effects of gender, age, and race on the pharmacokinetics of etoposide after intravenous administration of etoposide phosphate in cancer patients. Semin Oncol. 1996 Dec;23(6 Suppl 13):23-9. PubMed PMID: 8996572.

69: Kaul S, Srinivas NR, Igwemezie LN, Barbhaiya RH. A pharmacodynamic evaluation of hematologic toxicity observed with etoposide phosphate in the treatment of cancer patients. Semin Oncol. 1996 Dec;23(6 Suppl 13):15-22. PubMed PMID: 8996571.

70: Budman DR. Early studies of etoposide phosphate, a water-soluble prodrug. Semin Oncol. 1996 Dec;23(6 Suppl 13):8-14. Review. PubMed PMID: 8996570.

71: Schacter L. Etoposide phosphate: what, why, where, and how? Semin Oncol. 1996 Dec;23(6 Suppl 13):1-7. Review. PubMed PMID: 8996569.

72: Fields SZ, Budman DR, Young RR, Kreis W, Ingram R, Schulman P, Cherny RC, Wright J, Behr J, Snow C, Schacter LP. Phase I study of high-dose etoposide phosphate in man. Bone Marrow Transplant. 1996 Nov;18(5):851-6. PubMed PMID: 8932836.

73: Witterland AH, Koks CH, Beijnen JH. Etoposide phosphate, the water soluble prodrug of etoposide. Pharm World Sci. 1996 Oct;18(5):163-70. Review. PubMed PMID: 8933576.

74: Mummaneni V, Kaul S, Igwemezie LN, Newell DR, Porter D, Thomas H, Calvert AH, Winograd B, Barbhaiya RH. Bioequivalence assessment of etoposide phosphate and etoposide using pharmacodynamic and traditional pharmacokinetic parameters. J Pharmacokinet Biopharm. 1996 Aug;24(4):313-25. PubMed PMID: 9044163.

75: Politino M, Brown J, Usher JJ. Purification and characterization of an extracellular alkaline phosphatase from Penicillium chrysogenum. Prep Biochem Biotechnol. 1996 Aug-Nov;26(3-4):171-81. PubMed PMID: 8958566.

76: Chabot GG, Armand JP, Terret C, de Forni M, Abigerges D, Winograd B, Igwemezie L, Schacter L, Kaul S, Ropers J, Bonnay M. Etoposide bioavailability after oral administration of the prodrug etoposide phosphate in cancer patients during a phase I study. J Clin Oncol. 1996 Jul;14(7):2020-30. PubMed PMID: 8683232.

77: Kreis W, Budman DR, Vinciguerra V, Hock K, Baer J, Ingram R, Schacter LP, Fields SZ. Pharmacokinetic evaluation of high-dose etoposide phosphate after a 2-hour infusion in patients with solid tumors. Cancer Chemother Pharmacol. 1996;38(4):378-84. PubMed PMID: 8674162.

78: Millward MJ, Newell DR, Mummaneni V, Igwemezie LN, Balmanno K, Charlton CJ, Gumbrell L, Lind MJ, Chapman F, Proctor M, et al. Phase I and pharmacokinetic study of a water-soluble etoposide prodrug, etoposide phosphate (BMY-40481). Eur

J Cancer. 1995 Dec;31A(13-14):2409-11. PubMed PMID: 8652278.

79: Kaul S, Igwemezie LN, Stewart DJ, Fields SZ, Kosty M, Levithan N, Bukowski R, Gandara D, Goss G, O'Dwyer P, et al. Pharmacokinetics and bioequivalence of etoposide following intravenous administration of etoposide phosphate and etoposide in patients with solid tumors. J Clin Oncol. 1995 Nov;13(11):2835-41. PubMed PMID: 7595746.

80: Brooks DJ, Srinivas NR, Alberts DS, Thomas T, Igwemzie LM, McKinney LM, Randolph J, Schacter L, Kaul S, Barbhaiya RH. Phase I and pharmacokinetic study of etoposide phosphate. Anticancer Drugs. 1995 Oct;6(5):637-44. PubMed PMID: 8845473.

81: Hainsworth JD, Levitan N, Wampler GL, Belani CP, Seyedsadr MS, Randolph J, Schacter LP, Greco FA. Phase II randomized study of cisplatin plus etoposide phosphate or etoposide in the treatment of small-cell lung cancer. J Clin Oncol.

1995 Jun;13(6):1436-42. PubMed PMID: 7751890.

82: Greco FA, Hainsworth JD. Etoposide phosphate or etoposide with cisplatin in the treatment of small cell lung cancer: randomized phase II trial. Lung Cancer.

1995 Jun;12 Suppl 3:S85-95. PubMed PMID: 7551961.

83: Thompson DS, Greco A, Miller AA, Srinivas NR, Igwenezue KB, Hainsworth JD, Schacter LP, Kaul S, Barbhaiya RH, Garrow C, et al. A phase I study of etoposide

phosphate administered as a daily 30-minute infusion for 5 days. Clin Pharmacol Ther. 1995 May;57(5):499-507. PubMed PMID: 7768072.

84: Fields SZ, Igwemezie LN, Kaul S, Schacter LP, Schilder RJ, Litam PP, Himpler

BS, McAleer C, Wright J, Barbhaiya RH, et al. Phase I study of etoposide phosphate (etopophos) as a 30-minute infusion on days 1, 3, and 5. Clin Cancer Res. 1995 Jan;1(1):105-11. PubMed PMID: 9815892.

85: Sessa C, Zucchetti M, Cerny T, Pagani O, Cavalli F, De Fusco M, De Jong J, Gentili D, McDaniel C, Prins C, et al. Phase I clinical and pharmacokinetic study of oral etoposide phosphate. J Clin Oncol. 1995 Jan;13(1):200-9. PubMed PMID: 7799021.

86: Igwemezie LN, Kaul S, Barbhaiya RH. Assessment of toxicokinetics and toxicodynamics following intravenous administration of etoposide phosphate in beagle dogs. Pharm Res. 1995 Jan;12(1):117-23. PubMed PMID: 7724471.

87: Budman DR, Igwemezie LN, Kaul S, Behr J, Lichtman S, Schulman P, Vinciguerra

V, Allen SL, Kolitz J, Hock K, et al. Phase I evaluation of a water-soluble etoposide prodrug, etoposide phosphate, given as a 5-minute infusion on days 1, 3, and 5 in patients with solid tumors. J Clin Oncol. 1994 Sep;12(9):1902-9. PubMed PMID: 8083713.

88: Bregman CL, Buroker RA, Hirth RS, Crosswell AR, Durham SK. Etoposide- and BMY-40481-induced sensory neuropathy in mice. Toxicol Pathol. 1994 Sep-Oct;22(5):528-35. PubMed PMID: 7899782.

89: Schacter LP, Igwemezie LN, Seyedsadr M, Morgenthien E, Randolph J, Albert E,

Santabárbara P. Clinical and pharmacokinetic overview of parenteral etoposide phosphate. Cancer Chemother Pharmacol. 1994;34 Suppl:S58-63. PubMed PMID: 8070028.

90: Haisma HJ, Boven E, van Muijen M, De Vries R, Pinedo HM. Analysis of a conjugate between anti-carcinoembryonic antigen monoclonal antibody and alkaline

phosphatase for specific activation of the prodrug etoposide phosphate. Cancer Immunol Immunother. 1992;34(5):343-8. PubMed PMID: 1540981.

91: Doyle TW, Vyas DM. Second generation analogs of etoposide and mitomycin C. Cancer Treat Rev. 1990 Sep;17(2-3):127-31. Review. PubMed PMID: 2125529.

92: Rose WC, Basler GA, Trail PA, Saulnier M, Crosswell AR, Casazza AM. Preclinical antitumor activity of a soluble etoposide analog, BMY-40481-30. Invest New Drugs. 1990;8 Suppl 1:S25-32. PubMed PMID: 2380014.

93: Senter PD. Antitumor effects of antibody enzyme conjugates in combination with prodrugs. Front Radiat Ther Oncol. 1990;24:132-41; discussion 161-5. PubMed

PMID: 2341048.

94: Senter PD, Schreiber GJ, Hirschberg DL, Ashe SA, Hellström KE, Hellström I. Enhancement of the in vitro and in vivo antitumor activities of phosphorylated mitomycin C and etoposide derivatives by monoclonal antibody-alkaline phosphatase conjugates. Cancer Res. 1989 Nov 1;49(21):5789-92. PubMed PMID: 2790791.

95: Senter PD, Saulnier MG, Schreiber GJ, Hirschberg DL, Brown JP, Hellström I, Hellström KE. Anti-tumor effects of antibody-alkaline phosphatase conjugates in combination with etoposide phosphate. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4842-6. PubMed PMID: 3387440; PubMed Central PMCID: PMC280532