MedKoo product information:

Valspodar

PSC-833 is a non-immunosuppressive cyclosporin derivative that potently and specifically inhibits P-gp.  In vitro experiments indicate that PSC-833 interacts directly with P-gp with high affinity and probably interferes with the ATPase activity of P-gp. Studies in multidrug resistant tumor models confirm P-gp as the in vivo target of PSC-833 and demonstrate the ability of PSC-833 to reverse MDR leukemias and solid tumors in mice. Presently, PSC-833 is being evaluated in the clinic.

According to wikipedia.com. Previous studies in animal models have found it to be effective at preventing cancer cell resistance to chemotherapeutics, but these findings did not translate to clinical success. (http://en.wikipedia.org/wiki/Psc833).

Current developer:    Novartis Pharmaceuticals.

 1: Kolitz JE, George SL, Marcucci G, Vij R, Powell BL, Allen SL, DeAngelo DJ, Shea TC, Stock W, Baer MR, Hars V, Maharry K, Hoke E, Vardiman JW, Bloomfield CD, Larson RA; Cancer and Leukemia Group B. P-glycoprotein inhibition using valspodar (PSC-833) does not improve outcomes for patients younger than age 60 years with newly diagnosed acute myeloid leukemia: Cancer and Leukemia Group B study 19808. Blood. 2010 Sep 2;116(9):1413-21. Epub 2010 Jun 3. PubMed PMID: 20522709; PubMed Central PMCID: PMC2938834.

2: O'Brien MM, Lacayo NJ, Lum BL, Kshirsagar S, Buck S, Ravindranath Y, Bernstein M, Weinstein H, Chang MN, Arceci RJ, Sikic BI, Dahl GV. Phase I study of valspodar (PSC-833) with mitoxantrone and etoposide in refractory and relapsed pediatric acute leukemia: a report from the Children's Oncology Group. Pediatr Blood Cancer. 2010 May;54(5):694-702. PubMed PMID: 20209646; PubMed Central PMCID: PMC2838930.

3: Binkhathlan Z, Hamdy DA, Brocks DR, Lavasanifar A. Pharmacokinetics of PSC 833 (valspodar) in its Cremophor EL formulation in rat. Xenobiotica. 2010 Jan;40(1):55-61. PubMed PMID: 19903013.

4: Binkhathlan Z, Somayaji V, Brocks DR, Lavasanifar A. Development of a liquid chromatography-mass spectrometry (LC/MS) assay method for the quantification of PSC 833 (Valspodar) in rat plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2008 Jun 15;869(1-2):31-7. Epub 2008 May 10. PubMed PMID: 18514043.

5: Lhommé C, Joly F, Walker JL, Lissoni AA, Nicoletto MO, Manikhas GM, Baekelandt MM, Gordon AN, Fracasso PM, Mietlowski WL, Jones GJ, Dugan MH. Phase III study of valspodar (PSC 833) combined with paclitaxel and carboplatin compared with paclitaxel and carboplatin alone in patients with stage IV or suboptimally debulked stage III epithelial ovarian cancer or primary peritoneal cancer. J Clin Oncol. 2008 Jun 1;26(16):2674-82. PubMed PMID: 18509179.

6: Pein F, Pinkerton R, Berthaud P, Pritchard-Jones K, Dick G, Vassal G. Dose finding study of oral PSC 833 combined with weekly intravenous etoposide in children with relapsed or refractory solid tumours. Eur J Cancer. 2007 Sep;43(14):2074-81. Epub 2007 Aug 22. PubMed PMID: 17716890.

7: Kankesan J, Laconi E, Medline A, Thiessen JJ, Ling V, Rao PM, Rajalakshmi S, Sarma DS. PSC 833, an inhibitor of P-glycoprotein inhibits 1,2-dimethylhydrazine-induced colorectal carcinogenesis in male Fischer F344 rats. Anticancer Res. 2006 Mar-Apr;26(2A):995-9. PubMed PMID: 16619498.

8: Friedenberg WR, Rue M, Blood EA, Dalton WS, Shustik C, Larson RA, Sonneveld P, Greipp PR. Phase III study of PSC-833 (valspodar) in combination with vincristine, doxorubicin, and dexamethasone (valspodar/VAD) versus VAD alone in patients with recurring or refractory multiple myeloma (E1A95): a trial of the Eastern Cooperative Oncology Group. Cancer. 2006 Feb 15;106(4):830-8. PubMed PMID: 16419071.

9: Advani R, Lum BL, Fisher GA, Halsey J, Chin DL, Jacobs CD, Sikic BI. A phase I trial of liposomal doxorubicin, paclitaxel and valspodar (PSC-833), an inhibitor of multidrug resistance. Ann Oncol. 2005 Dec;16(12):1968-73. Epub 2005 Aug 26. PubMed PMID: 16126736.

10: van der Holt B, Löwenberg B, Burnett AK, Knauf WU, Shepherd J, Piccaluga PP, Ossenkoppele GJ, Verhoef GE, Ferrant A, Crump M, Selleslag D, Theobald M, Fey MF, Vellenga E, Dugan M, Sonneveld P. The value of the MDR1 reversal agent PSC-833 in addition to daunorubicin and cytarabine in the treatment of elderly patients with previously untreated acute myeloid leukemia (AML), in relation to MDR1 status at diagnosis. Blood. 2005 Oct 15;106(8):2646-54. Epub 2005 Jun 30. PubMed PMID: 15994288.

11: Bauer KS, Karp JE, Garimella TS, Wu S, Tan M, Ross DD. A phase I and pharmacologic study of idarubicin, cytarabine, etoposide, and the multidrug resistance protein (MDR1/Pgp) inhibitor PSC-833 in patients with refractory leukemia. Leuk Res. 2005 Mar;29(3):263-71. PubMed PMID: 15661261.

12: Kolitz JE, George SL, Dodge RK, Hurd DD, Powell BL, Allen SL, Velez-Garcia E, Moore JO, Shea TC, Hoke E, Caligiuri MA, Vardiman JW, Bloomfield CD, Larson RA; Cancer and Leukemia Group B. Dose escalation studies of cytarabine, daunorubicin, and etoposide with and without multidrug resistance modulation with PSC-833 in untreated adults with acute myeloid leukemia younger than 60 years: final induction results of Cancer and Leukemia Group B Study 9621. J Clin Oncol. 2004 Nov 1;22(21):4290-301. PubMed PMID: 15514371.

13: Cagliero E, Ferracini R, Morello E, Scotlandi K, Manara MC, Buracco P, Comandone A, Baroetto Parisi R, Baldini N. Reversal of multidrug-resistance using Valspodar (PSC 833) and doxorubicin in osteosarcoma. Oncol Rep. 2004 Nov;12(5):1023-31. PubMed PMID: 15492788.

14: Bustamante J, Caldas Lopes E, Garcia M, Di Libero E, Alvarez E, Hajos SE. Disruption of mitochondrial membrane potential during apoptosis induced by PSC 833 and CsA in multidrug-resistant lymphoid leukemia. Toxicol Appl Pharmacol. 2004 Aug 15;199(1):44-51. PubMed PMID: 15289089.

15: Bates SE, Bakke S, Kang M, Robey RW, Zhai S, Thambi P, Chen CC, Patil S, Smith T, Steinberg SM, Merino M, Goldspiel B, Meadows B, Stein WD, Choyke P, Balis F, Figg WD, Fojo T. A phase I/II study of infusional vinblastine with the P-glycoprotein antagonist valspodar (PSC 833) in renal cell carcinoma. Clin Cancer Res. 2004 Jul 15;10(14):4724-33. PubMed PMID: 15269145.

16: Friedenberg WR, Tallman MS, Brodsky I, Paietta E, Rowe JM, Lee SJ, Rowland KM Jr, Schnetzer GW, Reed JC. Modified VAD and PSC-833 in the treatment of resistant or relapsing chronic lymphocytic leukemia (E4996): a trial of the Eastern Cooperative Oncology Group. Leuk Res. 2004 Aug;28(8):813-9. PubMed PMID: 15203279.

17: Lacayo NJ, Duran GE, Sikic BI. Modulation of resistance to idarubicin by the cyclosporin PSC 833 (valspodar) in multidrug-resistant cells. J Exp Ther Oncol. 2003 May-Jun;3(3):127-35. PubMed PMID: 14641819.

18: Kankesan J, Vanama R, Yusuf A, Thiessen JJ, Ling V, Rao PM, Rajalakshmi S, Sarma DS. Effect of PSC 833, an inhibitor of P-glycoprotein on N-methyl-N-nitrosourea induced mammary carcinogenesis in rats. Carcinogenesis. 2004 Mar;25(3):425-30. Epub 2003 Nov 21. PubMed PMID: 14633655.

19: Kankesan J, Vanama R, Renlund R, Thiessen JJ, Ling V, Rao PM, Rajalakshmi S, Sarma DS. Source of a micro-nutrient in a semi-synthetic basal diet as a causative factor in inducing urinary calculi in rats and its inhibition by PSC 833, a potent inhibitor of P-glycoprotein. Comp Med. 2003 Aug;53(4):444-7. PubMed PMID: 14524422.

20: Kankesan J, Yusuf A, Laconi E, Vanama R, Bradley G, Thiessen JJ, Ling V, Rao PM, Rajalakshmi S, Sarma DS. Effect of PSC 833, an inhibitor of P-glycoprotein, on 1,2-dimethylhydrazine-induced liver carcinogenesis in rats. Carcinogenesis. 2003 Dec;24(12):1977-84. Epub 2003 Sep 11. PubMed PMID: 12970066.

21: Sadanand V, Kankesan J, Yusuf A, Stewart C, Rutka JT, Thiessen JJ, Ling V, Rao PM, Rajalakshmi S, Sarma DS. Effect of PSC 833, a potent inhibitor of P-glycoprotein, on the growth of astrocytoma cells in vitro. Cancer Lett. 2003 Jul 30;198(1):21-7. PubMed PMID: 12893426.

22: Merlin JL, Gautier H, Barberi-Heyob M, Teiten MH, Guillemin F. The multidrug resistance modulator SDZ-PSC 833 potentiates the photodynamic activity of chlorin e6 independently of P-glycoprotein in multidrug resistant human breast adenocarcinoma cells. Int J Oncol. 2003 Apr;22(4):733-9. PubMed PMID: 12632062.

23: Lopes EC, Garcia M, Benavides F, Shen J, Conti CJ, Alvarez E, Hajos SE. Multidrug resistance modulators PSC 833 and CsA show differential capacity to induce apoptosis in lymphoid leukemia cell lines independently of their MDR phenotype. Leuk Res. 2003 May;27(5):413-23. PubMed PMID: 12620293.

24: Gruber A, Björkholm M, Brinch L, Evensen S, Gustavsson B, Hedenus M, Juliusson G, Löfvenberg E, Nesthus I, Simonsson B, Sjo M, Stenke L, Tangen JM, Tidefelt U, Udén AM, Paul C, Liliemark J. A phase I/II study of the MDR modulator Valspodar (PSC 833) combined with daunorubicin and cytarabine in patients with relapsed and primary refractory acute myeloid leukemia. Leuk Res. 2003 Apr;27(4):323-8. PubMed PMID: 12531223.

25: Duraj J, Sedlak J, Bies J, Chovancova J, Chorvath B. PSC 833 modulation of multidrug resistance to paclitaxel in cultured human ovarian carcinoma cells leads to apoptosis. Anticancer Res. 2002 Nov-Dec;22(6A):3425-8. PubMed PMID: 12530099.

26: Wang H, Giuliano AE, Cabot MC. Enhanced de novo ceramide generation through activation of serine palmitoyltransferase by the P-glycoprotein antagonist SDZ PSC 833 in breast cancer cells. Mol Cancer Ther. 2002 Jul;1(9):719-26. PubMed PMID: 12479368.

27: Lehne G, Sørensen DR, Tjønnfjord GE, Beiske C, Hagve TA, Rugstad HE, Clausen OP. The cyclosporin PSC 833 increases survival and delays engraftment of human multidrug-resistant leukemia cells in xenotransplanted NOD-SCID mice. Leukemia. 2002 Dec;16(12):2388-94. PubMed PMID: 12454743.

28: Baer MR, George SL, Dodge RK, O'Loughlin KL, Minderman H, Caligiuri MA, Anastasi J, Powell BL, Kolitz JE, Schiffer CA, Bloomfield CD, Larson RA. Phase 3 study of the multidrug resistance modulator PSC-833 in previously untreated patients 60 years of age and older with acute myeloid leukemia: Cancer and Leukemia Group B Study 9720. Blood. 2002 Aug 15;100(4):1224-32. PubMed PMID: 12149202.

29: Dai H, Luo S, Yin A, Peng A. [Reversal of multidrug-resistance in human leukemia cell line K562/A02 by a cyclosporin D analogue PSC 833]. Zhonghua Xue Ye Xue Za Zhi. 2002 Jan;23(1):23-6. Chinese. PubMed PMID: 12015084.

30: Sonneveld P, Burnett A, Vossebeld P, Ben-Am M, Rosenkranz G, Pfister C, Verhoef G, Dekker A, Ossenkoppele G, Ferrant C, Yin L, Gratwohl A, Kovacsovics T, Vellenga E, Capdeville R, Löwenberg B. Dose-finding study of valspodar (PSC 833) with daunorubicin and cytarabine to reverse multidrug resistance in elderly patients with previously untreated acute myeloid leukemia. Hematol J. 2000;1(6):411-21. PubMed PMID: 11920222.

31: Liao M, Chen H, Shui H. [Apoptosis induced by cisplatin and verapamil or SDZ PSC 833 in human ovarian cell lines]. Zhonghua Fu Chan Ke Za Zhi. 2000 Feb;35(2):101-4. Chinese. PubMed PMID: 11809110.

32: Bates S, Kang M, Meadows B, Bakke S, Choyke P, Merino M, Goldspiel B, Chico I, Smith T, Chen C, Robey R, Bergan R, Figg WD, Fojo T. A Phase I study of infusional vinblastine in combination with the P-glycoprotein antagonist PSC 833 (valspodar). Cancer. 2001 Sep 15;92(6):1577-90. PubMed PMID: 11745237.

33: Uchiyama-Kokubu N, Watanabe T, Cohen D. Intracellular levels of two cyclosporin derivatives valspodar (PSC 833) and cyclosporin a closely associated with multidrug resistance-modulating activity in sublines of human colorectal adenocarcinoma HCT-15. Jpn J Cancer Res. 2001 Oct;92(10):1116-26. PubMed PMID: 11676863.

34: Azare J, Pankova-Kholmyansky I, Salnikow K, Cohen D, Flescher E. Selective susceptibility of transformed T lymphocytes to induction of apoptosis by PSC 833, an inhibitor of P-glycoprotein. Oncol Res. 2001;12(8):315-23. PubMed PMID: 11589302.

35: Lo Y, Liu F, Cherng J. Effect of PSC 833 liposomes and Intralipid on the transport of epirubicin in Caco-2 cells and rat intestines. J Control Release. 2001 Sep 11;76(1-2):1-10. PubMed PMID: 11532308.

36: Kang MH, Figg WD, Ando Y, Blagosklonny MV, Liewehr D, Fojo T, Bates SE. The P-glycoprotein antagonist PSC 833 increases the plasma concentrations of 6alpha-hydroxypaclitaxel, a major metabolite of paclitaxel. Clin Cancer Res. 2001 Jun;7(6):1610-7. PubMed PMID: 11410497.

37: Fracasso PM, Brady MF, Moore DH, Walker JL, Rose PG, Letvak L, Grogan TM, McGuire WP. Phase II study of paclitaxel and valspodar (PSC 833) in refractory ovarian carcinoma: a gynecologic oncology group study. J Clin Oncol. 2001 Jun 15;19(12):2975-82. PubMed PMID: 11408492.

38: Visani G, Milligan D, Leoni F, Chang J, Kelsey S, Marcus R, Powles R, Schey S, Covelli A, Isidori A, Litchman M, Piccaluga PP, Mayer H, Malagola M, Pfister C. Combined action of PSC 833 (Valspodar), a novel MDR reversing agent, with mitoxantrone, etoposide and cytarabine in poor-prognosis acute myeloid leukemia. Leukemia. 2001 May;15(5):764-71. PubMed PMID: 11368437.

39: Advani R, Fisher GA, Lum BL, Hausdorff J, Halsey J, Litchman M, Sikic BI. A phase I trial of doxorubicin, paclitaxel, and valspodar (PSC 833), a modulator of multidrug resistance. Clin Cancer Res. 2001 May;7(5):1221-9. PubMed PMID: 11350887.

40: Dorr R, Karanes C, Spier C, Grogan T, Greer J, Moore J, Weinberger B, Schiller G, Pearce T, Litchman M, Dalton W, Roe D, List AF. Phase I/II study of the P-glycoprotein modulator PSC 833 in patients with acute myeloid leukemia. J Clin Oncol. 2001 Mar 15;19(6):1589-99. Erratum in: J Clin Oncol 2001 May 1;19(9):2583. PubMed PMID: 11250987.

41: Drewe J, Gutmann H, Fricker G, Török M, Beglinger C, Huwyler J. HIV protease inhibitor ritonavir: a more potent inhibitor of P-glycoprotein than the cyclosporine analog SDZ PSC 833. Biochem Pharmacol. 1999 May 15;57(10):1147-52. PubMed PMID: 11230802.

42: Kreis W, Budman DR, Calabro A. A reexamination of PSC 833 (Valspodar) as a cytotoxic agent and in combination with anticancer agents. Cancer Chemother Pharmacol. 2001;47(1):78-82. PubMed PMID: 11221966.

43: Minami H, Ohtsu T, Fujii H, Igarashi T, Itoh K, Uchiyama-Kokubu N, Aizawa T, Watanabe T, Uda Y, Tanigawara Y, Sasaki Y. Phase I study of intravenous PSC-833 and doxorubicin: reversal of multidrug resistance. Jpn J Cancer Res. 2001 Feb;92(2):220-30. PubMed PMID: 11223552.

44: Duraj J, Takacsova X, Sedlak J, Sulikova M, Hunakova L, Bies J, Chorvath B. PSC 833 induces apoptosis in drug-sensitive human leukemia cell line and modulates resistance to paclitaxel in its multidrug-resistant variant. Anticancer Res. 2000 Nov-Dec;20(6B):4627-32. PubMed PMID: 11205313.

45: Chico I, Kang MH, Bergan R, Abraham J, Bakke S, Meadows B, Rutt A, Robey R, Choyke P, Merino M, Goldspiel B, Smith T, Steinberg S, Figg WD, Fojo T, Bates S. Phase I study of infusional paclitaxel in combination with the P-glycoprotein antagonist PSC 833. J Clin Oncol. 2001 Feb 1;19(3):832-42. PubMed PMID: 11157037.

46: Lopes EC, Scolnik M, Alvarez E, Hajos SE. Modulator activity of PSC 833 and cyclosporin-A in vincristine and doxorubicin-selected multidrug resistant murine leukemic cells. Leuk Res. 2001 Jan;25(1):85-93. PubMed PMID: 11137565.

47: Uchiyama-Kokubu N, Watanabe T, Nakajima M. A bioassay for the activity of PSC 833 in human serum for modulation of P-glycoprotein-mediated multidrug resistance. Anticancer Drugs. 2000 Aug;11(7):583-90. PubMed PMID: 11036963.

48: Chauncey TR, Rankin C, Anderson JE, Chen I, Kopecky KJ, Godwin JE, Kalaycio ME, Moore DF, Shurafa MS, Petersdorf SH, Kraut EH, Leith CP, Head DR, Luthardt FW, Willman CL, Appelbaum FR. A phase I study of induction chemotherapy for older patients with newly diagnosed acute myeloid leukemia (AML) using mitoxantrone, etoposide, and the MDR modulator PSC 833: a southwest oncology group study 9617. Leuk Res. 2000 Jul;24(7):567-74. PubMed PMID: 10867130.

49: Tidefelt U, Liliemark J, Gruber A, Liliemark E, Sundman-Engberg B, Juliusson G, Stenke L, Elmhorn-Rosenborg A, Möllgård L, Lehman S, Xu D, Covelli A, Gustavsson B, Paul C. P-Glycoprotein inhibitor valspodar (PSC 833) increases the intracellular concentrations of daunorubicin in vivo in patients with P-glycoprotein-positive acute myeloid leukemia. J Clin Oncol. 2000 May;18(9):1837-44. PubMed PMID: 10784624.

50: Fukushima T, Yamashita T, Takemura H, Suto H, Kishi S, Urasaki Y, Ueda T. Effect of PSC 833 on the cytotoxicity and pharmacodynamics of mitoxantrone in multidrug-resistant K562 cells. Leuk Res. 2000 Mar;24(3):249-54. PubMed PMID: 10739007.

51: Goulding CW, Giuliano AE, Cabot MC. SDZ PSC 833 the drug resistance modulator activates cellular ceramide formation by a pathway independent of P-glycoprotein. Cancer Lett. 2000 Feb 28;149(1-2):143-51. PubMed PMID: 10737718.

52: Estevez MD, Wolf A, Schramm U. Effect of PSC 833, verapamil and amiodarone on adriamycin toxicity in cultured rat cardiomyocytes. Toxicol In Vitro. 2000 Feb;14(1):17-23. PubMed PMID: 10699357.

53: Fracasso PM, Westervelt P, Fears CL, Rosen DM, Zuhowski EG, Cazenave LA, Litchman M, Egorin MJ. Phase I study of paclitaxel in combination with a multidrug resistance modulator, PSC 833 (Valspodar), in refractory malignancies. J Clin Oncol. 2000 Mar;18(5):1124-34. Erratum in: J Clin Oncol 2000 Jul;18(14):2793. Westerveldt, P [corrected to Westervelt, P]; Fears, CA [corrected to Fears, CL]. PubMed PMID: 10694566.

54: Krishna R, St-Louis M, Mayer LD. Increased intracellular drug accumulation and complete chemosensitization achieved in multidrug-resistant solid tumors by co-administering valspodar (PSC 833) with sterically stabilized liposomal doxorubicin. Int J Cancer. 2000 Jan 1;85(1):131-41. PubMed PMID: 10585596.

55: Lee EJ, George SL, Caligiuri M, Szatrowski TP, Powell BL, Lemke S, Dodge RK, Smith R, Baer M, Schiffer CA. Parallel phase I studies of daunorubicin given with cytarabine and etoposide with or without the multidrug resistance modulator PSC-833 in previously untreated patients 60 years of age or older with acute myeloid leukemia: results of cancer and leukemia group B study 9420. J Clin Oncol. 1999 Sep;17(9):2831-9. PubMed PMID: 10561359.

56: Krishna R, McIntosh N, Riggs KW, Mayer LD. Doxorubicin encapsulated in sterically stabilized liposomes exhibits renal and biliary clearance properties that are independent of valspodar (PSC 833) under conditions that significantly inhibit nonencapsulated drug excretion. Clin Cancer Res. 1999 Oct;5(10):2939-47. PubMed PMID: 10537363.

57: Wang LG, Liu XM, Budman DR, Kreis W. Synergistic effect of estramustine and [3'-keto-Bmtl]-[Val2]-cyclosporine (PSC 833) on the inhibition of androgen receptor phosphorylation in LNCaP cells. Biochem Pharmacol. 1999 Oct 1;58(7):1115-21. PubMed PMID: 10484069.

58: Bakker M, van der Graaf WT, Piers DA, Franssen EJ, Groen HJ, Smit EF, Kool W, Hollema H, Müller EA, De Vries EG. 99mTc-Sestamibi scanning with SDZ PSC 833 as a functional detection method for resistance modulation in patients with solid tumours. Anticancer Res. 1999 May-Jun;19(3B):2349-53. PubMed PMID: 10472354.

59: Song S, Suzuki H, Kawai R, Sugiyama Y. Effect of PSC 833, a P-glycoprotein modulator, on the disposition of vincristine and digoxin in rats. Drug Metab Dispos. 1999 Jun;27(6):689-94. PubMed PMID: 10348798.

60: Cabot MC, Giuliano AE, Han TY, Liu YY. SDZ PSC 833, the cyclosporine A analogue and multidrug resistance modulator, activates ceramide synthesis and increases vinblastine sensitivity in drug-sensitive and drug-resistant cancer cells. Cancer Res. 1999 Feb 15;59(4):880-5. PubMed PMID: 10029079.

61: Fukushima T, Yamashita T, Yoshio N, Misaki H, Yamauchi T, Imamura S, Urasaki Y, Ueda T. Effect of PSC 833 on the cytotoxicity of idarubicin and idarubicinol in multidrug-resistant K562 cells. Leuk Res. 1999 Jan;23(1):37-42. PubMed PMID: 9933133.

62: Grey MR, Burgess R, Fisher A, Yin JA. Effect on cell kill of addition of multidrug resistance modifiers cyclosporin A and PSC 833 to cytotoxic agents in chronic lymphocytic leukaemia. Leuk Res. 1999 Jan;23(1):29-35. PubMed PMID: 9933132.

63: Advani R, Saba HI, Tallman MS, Rowe JM, Wiernik PH, Ramek J, Dugan K, Lum B, Villena J, Davis E, Paietta E, Litchman M, Sikic BI, Greenberg PL. Treatment of refractory and relapsed acute myelogenous leukemia with combination chemotherapy plus the multidrug resistance modulator PSC 833 (Valspodar). Blood. 1999 Feb 1;93(3):787-95. PubMed PMID: 9920827.

64: Kusunoki N, Takara K, Tanigawara Y, Yamauchi A, Ueda K, Komada F, Ku Y, Kuroda Y, Saitoh Y, Okumura K. Inhibitory effects of a cyclosporin derivative, SDZ PSC 833, on transport of doxorubicin and vinblastine via human P-glycoprotein. Jpn J Cancer Res. 1998 Nov;89(11):1220-8. PubMed PMID: 9914792.

65: van Tellingen O, Kemper M, Tijssen F, van Asperen J, Nooijen WJ, Beijnen JH. High-performance liquid chromatographic bio-analysis of PSC 833 in human and murine plasma. J Chromatogr B Biomed Sci Appl. 1998 Nov 20;719(1-2):251-7. PubMed PMID: 9869389.

66: Song S, Suzuki H, Terasaki T, Lemaire M, Sugiyama Y. Modulation of the tumor disposition of vinca alkaloids by PSC 833 in vitro and in vivo. J Pharmacol Exp Ther. 1998 Dec;287(3):963-8. PubMed PMID: 9864280.

67: Robey R, Bakke S, Stein W, Meadows B, Litman T, Patil S, Smith T, Fojo T, Bates S. Efflux of rhodamine from CD56+ cells as a surrogate marker for reversal of P-glycoprotein-mediated drug efflux by PSC 833. Blood. 1999 Jan 1;93(1):306-14. PubMed PMID: 9864175.

68: Giaccone G, Linn SC, Welink J, Catimel G, Stieltjes H, van der Vijgh WJ, Eeltink C, Vermorken JB, Pinedo HM. A dose-finding and pharmacokinetic study of reversal of multidrug resistance with SDZ PSC 833 in combination with doxorubicin in patients with solid tumors. Clin Cancer Res. 1997 Nov;3(11):2005-15. PubMed PMID: 9815591.

69: Song S, Suzuki H, Kawai R, Tanaka C, Akasaka I, Sugiyama Y. Dose-dependent effects of PSC 833 on its tissue distribution and on the biliary excretion of endogenous substrates in rats. Drug Metab Dispos. 1998 Nov;26(11):1128-33. PubMed PMID: 9806956.

70: Atadja P, Watanabe T, Xu H, Cohen D. PSC-833, a frontier in modulation of P-glycoprotein mediated multidrug resistance. Cancer Metastasis Rev. 1998 Jun;17(2):163-8. Review. PubMed PMID: 9770112.

71: Lehne G, Rugstad HE. Cytotoxic effect of the cyclosporin PSC 833 in multidrug-resistant leukaemia cells with increased expression of P-glycoprotein. Br J Cancer. 1998 Sep;78(5):593-600. PubMed PMID: 9744497; PubMed Central PMCID: PMC2063045.

72: Sedlak J, Hunakova L, Chorvath M, Sulikova M, Novotny L, Boljesikova E, Zeillinger R, Chorvath B. Resistance of human multidrug-resistant neoplastic cell lines to paclitaxel-induced-radiosensitization is reduced by the non-immunosuppressive cyclosporine analog SDZ PSC 833. Anticancer Res. 1998 Jul-Aug;18(4C):3099-105. PubMed PMID: 9713517.

73: Massart C, Gibassier J, Denais A, Genetet N. Effect of PSC 833 on the efficacy of doxorubicin in vitro in a medullary thyroid carcinoma cell line. Anticancer Res. 1998 Jul-Aug;18(4C):2953-6. PubMed PMID: 9713490.

74: Norum J. Quality of life in colorectal cancer patients treated with doxorubicin and a multi-drug resistance (MDR) modulator (SDZ PSC-833): a pilot study. Anticancer Res. 1998 Jul-Aug;18(4C):2933-6. PubMed PMID: 9713487.

75: Cabot MC, Han TY, Giuliano AE. The multidrug resistance modulator SDZ PSC 833 is a potent activator of cellular ceramide formation. FEBS Lett. 1998 Jul 17;431(2):185-8. PubMed PMID: 9708899.

76: Fischer V, Rodríguez-Gascón A, Heitz F, Tynes R, Hauck C, Cohen D, Vickers AE. The multidrug resistance modulator valspodar (PSC 833) is metabolized by human cytochrome P450 3A. Implications for drug-drug interactions and pharmacological activity of the main metabolite. Drug Metab Dispos. 1998 Aug;26(8):802-11. PubMed PMID: 9698296.

77: den Boer ML, Pieters R, Kazemier KM, Janka-Schaub GE, Henze G, Veerman AJ. The modulating effect of PSC 833, cyclosporin A, verapamil and genistein on in vitro cytotoxicity and intracellular content of daunorubicin in childhood acute lymphoblastic leukemia. Leukemia. 1998 Jun;12(6):912-20. PubMed PMID: 9639420.

78: Jetté L, Murphy GF, Béliveau R. Drug binding to P-glycoprotein is inhibited in normal tissues following SDZ-PSC 833 treatment. Int J Cancer. 1998 May 29;76(5):729-37. PubMed PMID: 9610733.

79: Desrayaud S, De Lange EC, Lemaire M, Bruelisauer A, De Boer AG, Breimer DD. Effect of the Mdr1a P-glycoprotein gene disruption on the tissue distribution of SDZ PSC 833, a multidrug resistance-reversing agent, in mice. J Pharmacol Exp Ther. 1998 May;285(2):438-43. PubMed PMID: 9580581.

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