Valspodar

(BAN, USAN, rINN)
Synonyms: PSC-833; SDZ-PSC-833; Valspodarum. Cyclo{[(2S,4R,6E)-4-methyl-2-(methylamino)-3-oxo-6-octenoyl]N-methylmethyl
Cyrillic synonym: Вальсподар.

Chemical information

Chemical formula: C63H111N11O12 = 1214.6.
CAS — 121584-18-7.

Profile

Valspodar is an analogue of ciclosporin. It inhibits Pglycoprotein, which is associated with multidrug resistance. Valspodar is being investigated in various neoplasms to restore sensitivity of resistant tumour cells to anticancer drugs, but results have been disappointing. Valspodar inhibits the cytochrome P450 isoenzyme CYP3A4, and may reduce the metabolism and clearance of other drugs.
1. Advani, R, et al. Treatment of poor prognosis AML patients using PSC833 (valspodar) plus mitoxantrone, etoposide, and cytarabine (PSC-MEC). Adv Exp Med Biol 1999; 457: 47–56
2. Sparreboom A, Nooter K. Does P-glycoprotein play a role in anticancer drug pharmacokinetics? Drug Resist Updat 2000; 3: 357–63
3. Kang MH, et al. The P-glycoprotein antagonist PSC 833 increases the plasma concentrations of 6α-hydroxypaclitaxel, a major metabolite of paclitaxel. Clin Cancer Res 2001; 7: 1610–17
4. Fracasso PM, et al. Phase II study of paclitaxel and valspodar (PSC 833) in refractory ovarian carcinoma: a gynecologic oncology group study. J Clin Oncol 2001; 19: 2975–82
5. Baekelandt M, et al. Phase I/II trial of the multidrug-resistance modulator valspodar combined with cisplatin and doxorubicin in refractory ovarian cancer. J Clin Oncol 2001; 19: 2983–93
6. Baer MR, et al. 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; 100: 1224–32
7. Ma MK, et al. Pharmacokinetic study of infusional valspodar. J Clin Pharmacol 2002; 42: 412–18
8. Greenberg PL, et al. Mitoxantrone, etoposide, and cytarabine with or without valspodar in patients with relapsed or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome: a phase III trial (E2995). J Clin Oncol 2004; 22: 1078–86. Correction. ibid.; 2747
9. van der Holt B, et al. 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; 106: 2646–54
10. Friedenberg WR, et al. 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; 106: 830–8.
Published May 08, 2019.