Vismodegib: An Inhibitor of the Hedgehog Signaling Pathway in the Treatment of Basal Cell Carcinoma

Annals of Pharmacotherapy

Volumn 48, Issue 1, 2014, Pages 99-106

  Proctor, Amber E ^a   Thompson, Lisa A ^a   O'Bryant, Cindy L ^a  

^a UNIVERSITY OF COLORADO   (United States)

Author keywords

basal cell carcinoma; Hedgehog inhibitor; vismodegib

Indexed keywords

6 ETHYL 4,5 DIHYDRO N [1 (HYDROXYACETYL) 4 PIPERIDINYL] 1 METHYL 4 OXO 5 (2 OXO 2 PHENYLETHYL) 3 (2,2,2 TRIFLUOROETHOXY) 1H PYRROLO[3,2 C]PYRIDINE 2 CARBOXAMIDE; ANTINEOPLASTIC AGENT; BMS 833923; CYTOCHROME P450 2C9; CYTOCHROME P450 3A4; LEQ 506; PF 04449913; PROTEIN PATCHED 1; SARIDEGIB; SMOOTHENED PROTEIN; SONIC HEDGEHOG PROTEIN; SONIDEGIB; UNCLASSIFIED DRUG; VISMODEGIB; ZINC FINGER PROTEIN;

ADVANCED CANCER; ALOPECIA; BASAL CELL CARCINOMA; CELL PROLIFERATION; CELL SURVIVAL; DECREASED APPETITE; DIARRHEA; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG FATALITY; DRUG FORMULARY; DRUG GLUCURONIDATION; DRUG HALF LIFE; DRUG METABOLISM; DRUG OXIDATION; DRUG SAFETY; DRUG SOLUBILITY; DRUG TOLERABILITY; DYSGEUSIA; FATIGUE; FOOD AND DRUG ADMINISTRATION; HUMAN; LOSS OF FUNCTION MUTATION; MAXIMUM PLASMA CONCENTRATION; MAXIMUM TOLERATED DOSE; MEDLINE; MEDULLOBLASTOMA; METASTASIS; MULTICENTER STUDY (TOPIC); MUSCLE SPASM; NONHUMAN; ONCOGENE; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REGISTER; REVIEW; SIGNAL TRANSDUCTION; TRANSCRIPTION INITIATION; WEIGHT REDUCTION;

BASAL CELL CARCINOMA; HEDGEHOG INHIBITOR; VISMODEGIB;

ANILIDES; ANIMALS; ANTINEOPLASTIC AGENTS; CARCINOMA, BASAL CELL; DRUG INTERACTIONS; HEDGEHOG PROTEINS; HUMANS; PYRIDINES; SIGNAL TRANSDUCTION; SKIN NEOPLASMS;

EID: 84892874910     PISSN: 10600280     EISSN: 15426270     Source Type: Journal    
DOI: 10.1177/1060028013506696     Document Type: Review

References (51)

1. Christenson LJ,Borrowman TA,Vachon CM, et al.Incidence of basal cell and squamous cell carcinomas in a population younger than 40 years.JAMA. 2005;295:681-690.
2. Rogers H,Weinstock MA,Harris AR, et al.Incidence estimate of nonmelanoma skin cancer in the United States, 2006.Arch Dermatol. 2010;146:283-287.
3. Weiss GJ,Korn RL.Metastatic basal cell carcinoma in the era of hedgehog signaling pathway inhibitors.Cancer. 2012;118:5310-5319.
4. Thissen MRTM,Neumann MHA,Schouten LJ.A systematic review of treatment modalities for primary basal cell carcinomas.Arch Dermatol. 1999;135:1177-1183.
5. MillerSJGrekinRCNelsonKC. NCCN clinical practice guidelines in oncology: basal cell and squamous cell skin cancers. Version 2.2013. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp#site. Accessed September 3, 2013.
6. Wong CSM,Strange RC,Lear JT.Clinical review: basal cell carcinoma.BMJ. 2003;327:794-798.
7. Muzio LL.Nevoid basal cell carcinoma syndrome (Gorlin syndrome).Orphanet J Rare Dis. 2008;3:32.
8. Hahn H,Wicking C,Zaphiropoulous PG, et al.Mutations of the human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome.Cell. 1996;85:841-851.
9. Nüsslein-Volhard C,Wieschaus E.Mutations affecting segment number and polarity in Drosophila.Nature. 1980;287:795-801.
10. Scales SJ,de Sauvage FJ.Mechanisms of hedgehog pathway activation in cancer and implications for therapy.Trends Pharmacol Sci. 2009;30:303-312.
11. Villavicencio EH,Walterhouse DO,Iannaccone PM.The sonic hedgehog-patched-gli pathway in human development and disease.Am J Hum Genet. 2000;67:1047-1054.
12. Hammerschmidt M,Brook A,McMahon AP.The world according to hedgehog.Trends Genet. 1997;13:14-21.
13. Goppner D,Leverkus M.Basal cell carcinoma: from the molecular understanding of the pathogenesis to targeted therapy of progressive disease.J Skin Cancer. 2011;2011:650258.
14. Keeler RF.Teratogenic compounds of Veratrum californicum (Durand)-IV. First isolation of veratramine and alkaloid Q and A reliable method for isolation of cyclopamine.Phytochemistry. 1968;7:303-306.
15. Taipale J,Chen JK,Cooper MK, et al.Effects of oncogenic mutations in Smoothened and Patched can be reversed by cyclopamine.Nature. 2000;406:1005-1009.
16. Chen JK,Taipale J,Cooper MK,Beachy PA.Inhibition of hedgehog signaling by direct binding of cylopamine to smoothened.Genes Dev. 2002;16:2743-2748.
17. Yun JI,Kim HR,Park H,Kim SK,Lee J.Small molecule inhibitors of the Hedgehog signaling pathway for the treatment of cancer.Arch Pharm Res. 2012;35:1317-1333.
18. Robarge KD,Brunton SA,Castanedo GM, et al.GDC-0449: a potent inhibitor of the hedgehog pathway.Bioorg Med Chem Lett. 2009;19:5576-5581.
19. LoRusso PM,Rudin CM,Reddy JC, et al.Phase I trial of hedgehog pathway inhibitor vismodegib (GDC-0449) in patients with refractory, locally advanced or metastatic solid tumors.Clin Cancer Res. 2011;17:2502-2511.
20. Low JA,deSauvage FJ.Clinical experience with hedgehog pathway inhibitors.J Clin Oncol. 2010;28:5321-5326.
21. Wong H,Alicke B,West KA, et al.Pharmacokinetic-pharmacodynamic analysis of vismodegib in preclinical models of mutational and ligand-dependent hedgehog pathway activation.Clin Cancer Res. 2011;17:4682-4692.
22. San Francisco, CA: Genentech USA, Inc; 2012:.
23. Graham R,Hop C,Borin M, et al.Single- and multiple-dose intravenous and role pharmacokinetics of the hedgehog pathway inhibitor vismodegib in healthy female subjects.Br J Clin Pharmacol. 2012;74:788-796.
24. Graham RA,Lum BL,Cheeti S, et al.Pharmacokinetics of hedgehog pathway inhibitor vismodegib (GDC-0049) in patients with locally advanced or metastatic solid tumors: the role of alpha-1-acid glycoprotein binding.Clin Cancer Res. 2011;17:2512-2520.
25. Von Hoff DD,LoRusso PM,Rudin CM, et al.Inhibition of hedgehog pathway in advanced bases-cell carcinoma.N Engl J Med. 2009;361:1164-1172.
26. Giannetti AM,Wong H,Dijkgraaf GJ, et al.Identification, characterization, and implications of species-dependent plasma protein binding for the oral hedgehog pathway inhibitor vismodegib (GDC-0449).J Med Chem. 2011;54:2592-2601.
27. Graham RA,Lum BL,Morrison G, et al.A single dose mass balance study of the hedgehog pathway inhibitor vismodegib (GCD-0449) in humans using accelerator mass spectrometry.Drug Metab Dispos. 2011;39:1460-1467.
28. Wong H,Chen JZ,Chou B, et al.Preclinical assessment of the absorption, distribution, metabolism and excretion of GDC-0449 (2-chloro-N-(4-chloro-3-(puridin-2-yl)phenyl)-4-(methylsulfonyl)benzamide), an orally bioavailable systemic hedgehog signaling pathway inhibitor.Xenobiotia. 2009;39:850-861.
29. LoRusso PM,Jimeno A,Dy G, et al.Pharmacokinetic dose-scheduling study of hedgehog pathway inhibitor vismodegib (GDC-0449) in patients with locally advanced or metastatic sold tumors.Clin Cancer Res. 2011;17:5774-5782.
30. Sekulic A,Migden MR,Oro AE, et al.Efficacy and safety of vismodegib in advanced basal-cell carcinoma.N Engl J Med. 2012;366:2171-2179.
31. Tang JY,Mackay-Wiggan JM,Aszterbaum M, et al.Inhibiting the hedgehog pathway in patients with basal-cell nevus syndrome.N Engl J Med. 2012;366:2180-2188.
32. Sharma M,Kang SP,Karrison T, et al.Evaluation of food effect on pharmacokinetics of GDC-0449 in advanced solid tumor patients.J Clin Oncol. 2012;30:.
33. PazdurR. Vismodegib NDA approval letter: reference ID 3079097. http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2012/203388s000ltr.pdf. Accessed September 3, 2013.
34. Kimura H,Ng JM,Curran T.Transient inhibition of the hedgehog pathway in young mice causes permanent defect in bone structure.Cancer Cell. 2008;13:249-260.
35. Schneider FT,Schanzer A,Czupal CJ, et al.Sonic hedgehog acts as a negative regulator of beta-catenin signaling in the adult tongue epithelium.Am J Pathol. 2010;177:404-414.
36. Aasi S,Silkiss R,Tang JY, et al.New onset of keratoacanthomas after vismodegib treatment for locally advanced basal cell carcinomas: a report of 2 cases.JAMA Dermatol. 2013;149:242-243.
37. LoRusso PM,Piha-Paul SA,Mita M, et al.Co-administration of vismodegib with rosiglitazone or combined oral contraceptive in patients with locally advanced or metastatic solid tumors: a pharmacokinetic assessment of drug-drug interaction potential.Cancer Chemother Pharmacol. 2013;71:193-202.
38. Graham RA,Chang I,Jin JY, et al.Daily dosing of vismodegib to steady state does not prolong the QTc interval in healthy volunteers.J Cardiovasc Pharmacol. 2013;61:83-89.
39. Moeholt K,Aagaard H,Pfeiffer P,Hansen O.Platinum-based cytotoxic therapy in basal cell carcinoma: a review of the literature.Acta Oncol. 1996;35:677-682.
40. ClinicalTrials.gov. Clinical trials search page. http://www.clinicaltrials.gov/ct2/home. Accessed September 3, 2013.
41. Kaye S,Fehrenbacher L,Holloway R, et al.A phase II, randomized, placebo-controlled study of vismodegib as maintenance therapy in patients with ovarian cancer in second or third complete remission.Clin Cancer Res. 2012;18:6509-6518.
42. Berlin J,Bendell J,Hart LL, et al.A randomized phase II, of vismodegib versus placebo with FOLFOX or FOLFIRI and bevacizumab in patients with previously untreated metastatic colorectal cancer.Clin Cancer Res. 2013;19:258-267.
43. Catenacci DVT,Bahary N,Nattam SR, et al.Final analysis of a phase IB/randomized phase II study of gemcitabine (G) plus placebo (P) or vismodegib (V), a hedgehog (Hh) pathway inhibitor, in patients (pts) with metastatic pancreatic cancer (PC): a University of Chicago phase II consortium study.J Clin Oncol. 2013;31:abstr4012.
44. Cohen JD,Christos PJ,Kindler HL, et al.Vismodegib (V), a hedgehog (HH) pathway inhibitor, combined with FOLFOX for first-line therapy of patients (pts) with advanced gastric and gastroesophageal junction (GEJ) carcinoma: a New York Cancer Consortium led phase II randomized study.J Clin Oncol. 2013;31:abstr4011.
45. Kool M,Korshunov A,Remke M, et al.Molecular subgroups of medulloblastoma: an international meta-analysis of transcriptome, genetic aberrations, and clinical data of WNT, SHH, group 3 and group 4 medulloblastomas.Acta Neuropathol. 2012;123:473-484.
46. Rudin CM,Hann CL,Laterra J, et al.Treatment of medulloblastoma with hedgehog pathway inhibitor GDC-0449.N Engl J Med. 2009;361:1173-1178.
47. Gajjar AJ,Gururangan S,Qaddoumi IA, et al.A prospective phase II study to determine the efficacy of GDC 0449 (vismodegib) in adults with recurrent medulloblastoma (MB): a Pediatric Brain Tumor Consortium study (PBTC 25B).J Clin Oncol. 2013;31:.
48. Vismodegib Briefing Package: Pediatric ODAC Subcommittee Meeting. San Francisco, CA: Genentech, Inc; 2011. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM277585.pdf. Accessed September 3, 2013.
49. Yauch RL,Dijkgraaf GJ,Alicke B, et al.Smoothened mutation confers resistance to a hedgehog pathway inhibitor in medulloblastoma.Science. 2009;326:572-574.
50. Chang AL,Oro AE.Initial assessment of tumor regrowth after vismodegib in advanced basal cell carcinoma.Arch Dermatol. 2012;148:1324-1325.
51. Metcalfe C,de Sauvage FJ.Hedgehog fights back: mechanisms of acquired resistance against smoothened antagonists.Cancer Res. 2011;71:5057-5061.