Phase I study of everolimus in pediatric patients with refractory solid tumors

Journal of Clinical Oncology

Volumn 25, Issue 30, 2007, Pages 4806-4812

  Fouladi, Maryam ^a   Laningham, Fred ^a   Wu, Jianrong ^a   O'Shaughnessy, Melinda A ^a   Molina, Kristen ^a   Broniscer, Alberto ^a   Spunt, Sheri L ^a   Luckett, Inga ^a   Stewart, Clinton F ^a   Houghton, Peter J ^a   Gilbertson, Richard J ^a   Furman, Wayne L ^a  

^a ST JUDE CHILDREN S RESEARCH HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EVEROLIMUS; MAMMALIAN TARGET OF RAPAMYCIN INHIBITOR; ANTINEOPLASTIC AGENT; DRUG DERIVATIVE; RAPAMYCIN;

ADOLESCENT; ADULT; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ANOREXIA; AREA UNDER THE CURVE; ARTICLE; CHILD; CHILDHOOD CANCER; CLINICAL ARTICLE; CLINICAL TRIAL; DIARRHEA; DIZZINESS; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DOSE COMPARISON; DRUG DOSE REDUCTION; DRUG MECHANISM; DRUG TOLERABILITY; DYSPNEA; FEMALE; GLUCOSE BLOOD LEVEL; HEMOGLOBIN BLOOD LEVEL; HUMAN; HUMAN CELL; HUMAN TISSUE; HYPOKALEMIA; HYPOPHOSPHATEMIA; INFECTION SENSITIVITY; LABORATORY TEST; LEUKOCYTE COUNT; MALE; MAXIMUM TOLERATED DOSE; MOUTH PAIN; MUCOSA INFLAMMATION; MULTIPLE CYCLE TREATMENT; NAUSEA; NEUTROPHIL COUNT; PERIPHERAL BLOOD MONONUCLEAR CELL; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; SIDE EFFECT; SODIUM BLOOD LEVEL; SOLID TUMOR; TREATMENT RESPONSE; TUMOR RECURRENCE; DOSE RESPONSE; DRUG ADMINISTRATION; METABOLISM; NEOPLASM; ORAL DRUG ADMINISTRATION; PRESCHOOL CHILD; SALVAGE THERAPY; SURVIVAL RATE; TREATMENT OUTCOME;

ADMINISTRATION, ORAL; ADOLESCENT; ADULT; ANTINEOPLASTIC AGENTS; CHILD; CHILD, PRESCHOOL; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG ADMINISTRATION SCHEDULE; FEMALE; HUMANS; MALE; MAXIMUM TOLERATED DOSE; NEOPLASMS; SALVAGE THERAPY; SIROLIMUS; SURVIVAL RATE; TREATMENT OUTCOME;

EID: 36049023679     PISSN: 0732183X     EISSN: None     Source Type: Journal    
DOI: 10.1200/JCO.2007.11.4017     Document Type: Article

References (42)

1. Shayesteh L, Lu Y, Kuo WL, et al: PIK3CA is implicated as an oncogene in ovarian cancer. Nat Genet 21:99-102, 1999
2. Li SY, Rong M, Grieu F, et al: PIK3CA mutations in breast cancer are associated with poor outcome. Breast Cancer Res Treat 96:91-95, 2006
3. Li J, Yen C, Liaw D, et al: PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 275:1943-1947, 1997
4. Shaw RJ, Bardeesy N, Manning BD, et al: The LKB1 tumor suppressor negatively regulates mTOR signaling. Cancer Cell 6:91-99, 2004
5. Liu L, Cash TP, Jones RG, et al: Hypoxia-induced energy stress regulates mRNA translation and cell growth. Mol Cell 21:521-531, 2006
6. Wong AS, Kim SO, Leung PC, et al: Profiling of protein kinases in the neoplastic transformation of human ovarian surface epithelium. Gynecol Oncol 82:305-311, 2001
7. Sorrells DL, Meschonat C, Black D, et al: Pattern of amplification and overexpression of the eukaryotic initiation factor 4E gene in solid tumor. J Surg Res 85:37-42, 1999
8. Samuels Y, Wang Z, Bardelli A, et al: High frequency of mutations of the PIK3CA gene in human cancers. Science 304:554, 2004
9. Bjornsti MA, Houghton PJ: The TOR pathway: A target for cancer therapy. Nat Rev Cancer 4:335-348, 2004
10. Sarbassov DD, Ali SM, Sabatini DM: Growing roles for the mTOR pathway. Curr Opin Cell Biol 17:596-603, 2005
11. Wullschleger S, Loewith R, Hall MN: TOR signaling in growth and metabolism. Cell 124:471-484, 2006
12. Sarbassov DD, Guertin DA, Ali SM, et al: Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 307:1098-1101, 2005
13. Boulay A, Zumstein-Mecker S, Stephan C, et al: Antitumor efficacy of intermittent treatment schedules with the rapamycin derivative RAD001 correlates with prolonged inactivation of ribosomal protein S6 kinase 1 in peripheral blood mononuclear cells. Cancer Res 64:252-261, 2004
14. Majumder PK, Febbo PG, Bikoff R, et al: MTOR inhibition reverses Akt-dependent prostate intraepithelial neoplasia through regulation of apoptotic and HIF-1-dependent pathways. Nat Med 10:594-601, 2004
15. Sarbassov DD, Ali SM, Sengupta S, et al: Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB. Mol Cell 22:159-168, 2006
16. Zeng Z, Sarbassov DD, Samudio IJ, et al: Rapamycin derivatives reduce mTORC2 signaling and inhibit AKT activation in AML. Blood 109:3509-3512, 2007
17. Guba M, von Breitenbuch P, Steinbauer M, et al: Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis: Involvement of vascular endothelial growth factor. Nat Med 8:128-135, 2002
18. Torres-Arzayus MI, Yuan J, DellaGatta JL, et al: Targeting the AIB1 oncogene through mammalian target of rapamycin inhibition in the mammary gland. Cancer Res 66:11381-11388, 2006
19. Aguirre D, Boya P, Bellet D, et al: Bcl-2 and CCND1/CDK4 expression levels predict the cellular effects of mTOR inhibitors in human ovarian carcinoma. Apoptosis 9:797-805, 2004
20. Treeck O, Wackwitz B, Haus U, et al: Effects of a combined treatment with mTOR inhibitor RAD001 and tamoxifen in vitro on growth and apoptosis of human cancer cells. Gynecol Oncol 102:292-299, 2006
21. Haritunians T, Mori A, O'Kelly J, et al: Antiproliferative activity of RAD001 (everolimus) as a single agent and combined with other agents in mantle cell lymphoma. Leukemia 21:333-339, 2007
22. Cao C, Subhawong T, Albert JM, et al: Inhibition of mammalian target of rapamycin or apoptotic pathway induces autophagy and radiosensitizes PTEN null prostate cancer cells. Cancer Res 66:10040-10047, 2006
23. Rossi F, Ehlers I, Agosti V, et al: Oncogenic Kit signaling and therapeutic intervention in a mouse model of gastrointestinal stromal tumor. Proc Natl Acad Sci U S A 103:12843-12848, 2006
24. Beuvink I, Boulay A, Fumagalli S, et al: The mTOR inhibitor RAD001 sensitizes tumor cells to DNA-damaged induced apoptosis through inhibition of p21 translation. Cell 120:747-759, 2005
25. Lane HA, Boulay A, Fumagalli S: The orally active rapamycin derivative RAD001 has potential as an antitumor agent with a broad antiproliferative activity: PTEN as a molecular determinant of response. Proc Am Assoc Cancer Res-NCI-EORTC 44, 2003 (abstr 1608)
26. Goudar RK, Shi Q, Hjelmeland MD, et al: Combination therapy of inhibitors of epidermal growth factor receptor/vascular endothelial growth factor receptor 2 (AEE788) and the mammalian target of rapamycin (RAD001) offers improved glioblastoma tumor growth inhibition. Mol Cancer Ther 4:101-112, 2005
27. O'Reilly T, Vaxelaire J, Muller M: In vivo activity of RAD001, an orally active rapamycin derivative in experimental tumor models. Proc Am Assoc Cancer Res 43, 2002 (abstr 359)
28. Dilling MB, Dias P, Shapiro DN, et al: Rapamycin selectively inhibits the growth of childhood rhabdomyosarcoma cells through inhibition of signaling via the type I insulin-like growth factor receptor. Cancer Res 54:903-907, 1994
29. Hosoi H, Dilling MB, Liu LN, et al: Studies on the mechanism of resistance to rapamycin in human cancer cells. Mol Pharmacol 54:815-824, 1998
30. Geoerger B, Kerr K, Tang CB, et al: Antitumor activity of the rapamycin analog CCI-779 in human primitive neuroectodermal tumor/medulloblastoma models as single agent and in combination chemotherapy. Cancer Res 61:1527-1532, 2001
31. Dudkin L, Dilling MB, Cheshire PJ, et al: Biochemical correlates of mTOR inhibition by the rapamycin ester CCI-779 and tumor growth inhibition. Clin Cancer Res 7:1758-1764, 2001
32. Yee KW, Zeng Z, Konopleva M, et al: Phase I/II study of the mammalian target of rapamycin inhibitor everolimus (RAD001) in patients with relapsed or refractory hematologic malignancies. Clin Cancer Res 12:5165-5173, 2006
33. Therasse P, Arbuck SG, Eisenhauer EA, et al: New guidelines to evaluate the response to treatment in solid tumors: European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205-216, 2000
34. Koal T, Deters M, Casetta B, et al: Simultaneous determination of four immunosuppressants by means of high speed and robust on-line solid phase extraction-high performance liquid chromatographytandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 805:215-222, 2004
35. Gilbertson RJ, Perry RH, Kelly PJ, et al: Prognostic significance of HER2 and HER4 coexpression in childhood medulloblastoma. Cancer Res 57:3272-3280, 1997
36. Calabrese C, Frank A, Maclean K, et al: Medulloblastoma sensitivity to 17-allylamino-17-demethoxygeldanamycin requires MEK/ERKM. J Biol Chem 278:24951-24959, 2003
37. Calabrese C, Poppleton H, Kocak M, et al: A perivascular niche for brain tumor stem cells. Cancer Cell 11:69-82, 2007
38. Gajjar A, Hernan R, Kocak M, et al: Clinical, histopathologic, and molecular markers of prognosis: Toward a new disease risk stratification system for medulloblastoma. J Clin Oncol 22:984-993, 2004
39. Kirchner GI, Meier-Wiedenbach I, Manns MP: Clinical pharmacokinetics of everolimus. Clin Pharmacokinet 43:83-95, 2004
40. O'Reilly KE, Rojo F, She QB, et al: MTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res 66:1500-1508, 2006
41. Sun SY, Rosenberg LM, Wang X, et al: Activation of Akt and eIF4E survival pathways by rapamycin-mediated mammalian target of rapamycin inhibition. Cancer Res 65:7052-7058, 2005
42. Dancey JE: Therapeutic targets: MTOR and related pathways. Cancer Biol Ther 5:1065-1073, 2006