A phase I study of bevacizumab (B) in combination with everolimus (E) and erlotinib (E) in advanced cancer (BEE)

Cancer Chemotherapy and Pharmacology

Volumn 67, Issue 2, 2011, Pages 465-474

  Bullock, Karen E ^a,c   Petros, William P ^b   Younis, Islam ^b,d   Uronis, Hope E ^a   Morse, Michael A ^a   Blobe, Gerard C ^a   Zafar, S Yousuf ^a   Gockerman, Jon P ^a   Lager, Joanne J ^a,e   Truax, Roxanne ^a   Meadows, Kellen L ^a   Howard, Leigh A ^a   O'Neill, Margot M ^a   Broadwater, Gloria ^a   Hurwitz, Herbert I ^a   Bendell, Johanna C ^a,f  

^a DUKE UNIVERSITY   (United States)

^b WEST VIRGINIA UNIVERSITY   (United States)

^c Space and Naval Warfare Systems Center Pacific   (United States)

^d CENTER FOR DRUG EVALUATION AND RESEARCH   (United States)

^e Global Health Outcomes and Market Access   (United States)

^f SARAH CANNON RESEARCH INSTITUTE   (United States)

Author keywords

Advanced cancer; Bevacizumab; Erlotinib; Everolimus; Phase I

Indexed keywords

BEVACIZUMAB; ERLOTINIB; EVEROLIMUS; ANGIOGENESIS INHIBITOR; ANTINEOPLASTIC AGENT; DRUG DERIVATIVE; MONOCLONAL ANTIBODY; PROTEIN KINASE INHIBITOR; QUINAZOLINE DERIVATIVE; RAPAMYCIN;

ADULT; ADVANCED CANCER; AGED; ANEMIA; AREA UNDER THE CURVE; ARTICLE; BREAST CANCER; CANCER COMBINATION CHEMOTHERAPY; CARCINOMA; CLINICAL ARTICLE; COLORECTAL CANCER; CONSTIPATION; DIARRHEA; DIGESTIVE SYSTEM CANCER; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG ERUPTION; DRUG INDUCED HEADACHE; DRUG SAFETY; DRUG TOLERABILITY; ENDOMETRIUM CANCER; ENTEROCOLITIS; FATIGUE; FEMALE; GASTROINTESTINAL HEMORRHAGE; HUMAN; HYPERGLYCEMIA; HYPERLIPIDEMIA; HYPERTENSION; INFECTION; INTERSTITIAL NEPHRITIS; KIDNEY CANCER; LIFE EXPECTANCY; LUNG NON SMALL CELL CANCER; MALE; MAXIMUM PLASMA CONCENTRATION; MUCOSA INFLAMMATION; NAUSEA; NEUTROPENIA; NEUTROPHIL COUNT; NOSE SEPTUM PERFORATION; OVARY CANCER; PANCREAS CANCER; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; PROCTITIS; PROGRESSION FREE SURVIVAL; PROTEINURIA; SARCOMA; SIDE EFFECT; SINUSITIS; STRENGTH; THROMBOCYTOPENIA; THROMBOEMBOLISM; UPREGULATION; VOMITING; WOUND HEALING; CLINICAL TRIAL; DISEASE FREE SURVIVAL; MAXIMUM TOLERATED DOSE; MIDDLE AGED; NEOPLASM; PATHOLOGY; TREATMENT OUTCOME;

ADULT; AGED; ANGIOGENESIS INHIBITORS; ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; DISEASE-FREE SURVIVAL; FEMALE; HUMANS; MALE; MAXIMUM TOLERATED DOSE; MIDDLE AGED; NEOPLASMS; PROTEIN KINASE INHIBITORS; QUINAZOLINES; SIROLIMUS; TREATMENT OUTCOME;

EID: 79953770512     PISSN: 03445704     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00280-010-1507-6     Document Type: Article

References (50)

1. Ciardiello F, Tortora G (2003) Epidermal growth factor receptor (EGFR) as a target in cancer therapy: understanding the role of receptor expression and other molecular determinants that could influence the response to anti-EGFR drugs. Eur J Cancer 39:1348-1354 (Pubitemid 36773776)
2. Ciardiello F, Tortora G (2008) EGFR antagonists in cancer treatment. N Engl J Med 358:1160-1174
3. Grant S (2008) Cotargeting survival signaling pathways in cancer. The Journal of clinical investigation 118:3003-3006
4. Hicklin DJ, Ellis LM (2005) Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol 23:1011-1027 (Pubitemid 46202320)
5. Meric-Bernstam F, Gonzalez-Angulo AM (2009) Targeting the mTOR signaling network for cancer therapy. J Clin Oncol 27:2278-2287
6. Fukumura D, Jain RK (2007) Tumor microenvironment abnormalities: causes, consequences, and strategies to normalize. J Cell Biochem 101:937-949 (Pubitemid 47040874)
7. Hudson CC, Liu M, Chiang GG, Otterness DM, Loomis DC, Kaper F, Giaccia AJ, Abraham RT (2002) Regulation of hypoxiainducible factor 1alpha expression and function by the mammalian target of rapamycin. Mol Cell Biol 22:7004-7014
8. Kerbel RS (2008) Tumor angiogenesis. N Engl J Med 358:2039-2049 (Pubitemid 351656458)
9. Hainsworth JD, Sosman JA, Spigel DR, Edwards DL, Baughman C, Greco A (2005) Treatment of metastatic renal cell carcinoma with a combination of bevacizumab and erlotinib. J Clin Oncol 23:7889-7896 (Pubitemid 46657387)
10. Herbst RS, Prager D, Hermann R, Fehrenbacher L, Johnson BE, Sandler A, Kris MG, Tran HT, Klein P, Li X, Ramies D, Johnson DH, Miller VA (2005) TRIBUTE: a phase III trial of erlotinib hydrochloride (OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol 23:5892-5899
11. Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350:2335-2342 (Pubitemid 38702844)
12. Saltz LB, Lenz HJ, Kindler HL, Hochster HS, Wadler S, Hoff PM, Kemeny NE, Hollywood EM, Gonen M, Quinones M, Morse M, Chen HX (2007) Randomized phase II trial of cetuximab, bevacizumab, and irinotecan compared with cetuximab and bevacizumab alone in irinotecan-refractory colorectal cancer: the BOND-2 study. J Clin Oncol 25:4557-4561 (Pubitemid 350035312)
13. Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R, Johnson DH (2006) Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355:2542-2550 (Pubitemid 44917502)
14. Wu W, Onn A, Isobe T, Itasaka S, Langley RR, Shitani T, Shibuya K, Komaki R, Ryan AJ, Fidler IJ, Herbst RS, O'Reilly MS (2007) Targeted therapy of orthotopic human lung cancer by combined vascular endothelial growth factor and epidermal growth factor receptor signaling blockade. Mol Cancer Ther 6:471-483 (Pubitemid 46332449)
15. Goudar RK, Shi Q, Hjelmeland MD, Keir ST, McLendon RE, Wikstrand CJ, Reese ED, Conrad CA, Traxler P, Lane HA, Reardon DA, Cavenee WK, Wang XF, Bigner DD, Friedman HS, Rich JN (2005) 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 (Pubitemid 40268071)
16. Buck E, Eyzaguirre A, Brown E, Petti F, McCormack S, Haley JD, Iwata KK, Gibson NW, Griffin G (2006) Rapamycin synergizes with the epidermal growth factor receptor inhibitor erlotinib in non-small-cell lung, pancreatic, colon, and breast tumors. Mol Cancer Ther 5:2676-2684 (Pubitemid 44848994)
17. Buck E, Eyzaguirre A, Haley JD, Gibson NW, Cagnoni P, Iwata KK (2006) Inactivation of Akt by the epidermal growth factor receptor inhibitor erlotinib is mediated by HER-3 in pancreatic and colorectal tumor cell lines and contributes to erlotinib sensitivity. Mol Cancer Ther 5:2051-2059 (Pubitemid 44336577)
18. Bianco R, Garofalo S, Rosa R, Damiano V, Gelardi T, Daniele G, Marciano R, Ciardiello F, Tortora G (2008) Inhibition of mTOR pathway by everolimus cooperates with EGFR inhibitors in human tumours sensitive and resistant to anti-EGFR drugs. Br J Cancer 98:923-930 (Pubitemid 351341618)
19. O'Reilly T, Lane HA, Wood JM, Schnell C, Littlewood-Evans A, Brueggen J, McSheehy PM (2010) Everolimus and PTK/ZK show synergistic growth inhibition in the orthotopic BL16/BL6 murine melanoma model. Cancer Chemother Pharmacol. Published online 30 May 2010
20. Simon R, Freidlin B, Rubinstein L, Arbuck SG, Collins J, Christian MC (1997) Accelerated titration designs for phase I clinical trials in oncology. J Natl Cancer Inst 89:1138-1147 (Pubitemid 27337928)
21. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG (2000) 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. Journal of the National Cancer Institute 92:205-216
22. Brignol N, McMahon LM, Luo S, Tse FL (2001) Highthroughput semi-automated 96-well liquid/liquid extraction and liquid chromatography/mass spectrometric analysis of everolimus (RAD 001) and cyclosporin a (CsA) in whole blood. Rapid Commun Mass Spectrom 15:898-907 (Pubitemid 32587177)
23. Hamilton M, Wolf JL, Rusk J, Beard SE, Clark GM, Witt K, Cagnoni PJ (2006) Effects of smoking on the pharmacokinetics of erlotinib. Clin Cancer Res 12:2166-2171
24. Milton DT, Riely GJ, Azzoli CG, Gomez JE, Heelan RT, Kris MG, Krug LM, Pao W, Pizzo B, Rizvi NA, Miller VA (2007) Phase 1 trial of everolimus and gefitinib in patients with advanced nonsmall-cell lung cancer. Cancer 110:599-605 (Pubitemid 47106149)
25. Papadimitrakopoulou V, Blumenschein GR, Leighl NB, Bennouna J, Soria JC, Burris I HA, Dimitrijevic S, Kunz T, Di Scala L, Johnson BE (2008) A phase 1/2 study investigating the combination of RAD001 (R) (everolimus) and erlotinib (E) as 2nd and 3rd line therapy in patients (pts) with advanced non-small cell lung cancer (NSCLC) previously treated with chemotherapy (C): Phase 1 results. J Clin Oncol 26: May 20 suppl abst 8051
26. Robins HI, Wen PY, Chang SM, Kuhn J, Lamborn K, Cloughesy T, Glibert MR, Yung WK, Dancey J, Prados MD (2007) Phase I study of erlotinib and CCI-779 (temsirolimus) for patients with recurrent malignant gliomas (MG) (NABTC 04-02). J Clin Oncol 25:18 S June 20 suppl abst 2057
27. Howard LA, Bullock KE, Bendell JC, Uronis HE, Vlahovic G., Blobe GC, Riedel RF, Nixon AB, Gockerman JP, Hurwitz HI (2009) Bevacizumab (B) plus everolimus (E) and panitumumab (P) in refractory advanced solid tumors. J Clin Oncol 27:15S abstr 3551
28. Flechner SM (2008) Reviewing the evidence for de novo immunosuppression with sirolimus. Transpl Proc 40: S25-S28
29. Chawla SP, Tolcher AW, Staddon AP, Schuetze S, D'Amato GZ, Blay JY, Loewy J, Kan R, Demetri GD (2007) Survival results with AP23573, a novel mTOR inhibitor, in patients (pts) with advanced soft tissue or bone sarcomas: Update of phase II trial. J Clin Oncol 25:18S (June Suppl abstr10076)
30. Duran I, Le L, Saltman D, Kortmansky J, Kocha W, Singh D, Pond GR, Peralba JM, Dancey J, Siu LL (2005) A phase II trial of temsirolimus in metastatic neuroendocrine carcinomas (NECs) J Clin Oncol: 16 S (June 1 Suppl abstr 3096)
31. Raymond E, Niccoli P, Raoul J, Bang Y, Borbath I, Lombard-Bohas C, Valle JW, Patyna S, Chao RC, Lu D (2010) Cox proportional hazard analysis of sunitinib (SU) efficacy across subgroups of patients (pts) with progressive pancreatic neuroendocrine tumors (NET). J Clin Oncol 28:15S (abstr 4031)
32. Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, Negrier S, Chevreau C, Solska E, Desai AA, Rolland F, Demkow T, Hutson TE, Gore M, Freeman S, Schwartz B, Shan M, Simantov R, Bukowski RM (2007) Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 356:125-134 (Pubitemid 46089673)
33. Escudier B, Pluzanska A, Koralewski P, Ravaud A, Bracarda S, Szczylik C, Chevreau C, Filipek M, Melichar B, Bajetta E, Gorbunova V, Bay JO, Bodrogi I, Jagiello-Gruszfeld A, Moore N (2007) Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet 370:2103-2111 (Pubitemid 350296300)
34. Hudes G, Carducci M, Tomczak P, Dutcher J, Figlin R, Kapoor A, Staroslawska E, Sosman J, McDermott D, Bodrogi I, Kovacevic Z, Lesovoy V, Schmidt-Wolf IG, Barbarash O, Gokmen E, O'Toole T, Lustgarten S, Moore L, Motzer RJ (2007) Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. NEngl J Med 356:2271-2281 (Pubitemid 46849157)
35. Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, Grunwald V, Thompson JA, Figlin RA, Hollaender N, Urbanowitz G, Berg WJ, Kay A, Lebwohl D, Ravaud A (2008) Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 372:449-456
36. Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, Oudard S, Negrier S, Szczylik C, Kim ST, Chen I, Bycott PW, Baum CM, Figlin RA (2007) Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 356:115-124 (Pubitemid 46089672)
37. Yao JC, Phan AT, Chang DZ, Wolff RA, Hess K, Gupta S, Jacobs C, Mares JE, Landgraf AN, Rashid A, Meric-Bernstam F (2008) Efficacy of RAD001 (everolimus) and octreotide LAR in advanced low-to intermediate-grade neuroendocrine tumors: results of a phase II study. J Clin Oncol 26:4311-4318
38. Sternberg CN, Szczylik C, Lee E, Salman PV, Mardiak J, Davis ID, Pandite L, Chen M, McCann L, Hawki R (2009) A randomized, double-blind phase III study of pazopanib in treatmentnaive and cytokine-pretreated patients with advanced renal cell carcinoma (RCC). J Clin Oncol 27:15S abstr 5021
39. Yao J, Shah M, Ito T, Lombard-Bohas C, Wolin E, Van Cutsem E, Hobday T, Sachs C, Hoosen S, Lincy J, David Lebwohl, Oberg K (2010) Everolimus versus placebo in patients with advanced pancreatic neuroendocrine tumors (pNET) (RADIANT-3). Presented at the World Congress on Gastrointestinal Cancer, July 2010 Poster O-0028
40. Sankhala KK, Chawla SP, Iagaru A, Dellamaggiora R, Chua V, Daly S, Bedrosian CL, Edwards GK, Cohen S, Demetri GD, Group ASS (2005) Early response evaluation of therapy with AP23573 (an mTOR inhibitor) in sarcoma using [18F]2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) scan J Clin Oncol 23:16S June 1 Suppl abstr 9028
41. Giantonio BJ, Catalano PJ, Meropol NJ, O'Dwyer PJ, Mitchell EP, Alberts SR, Schwartz MA, Benson III AB (2007) Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol 25:1539-1544 (Pubitemid 46733080)
42. Saltz LB, Rosen LS, Marshall JL, Belt RJ, Hurwitz HI, Eckhardt SG, Bergsland EK, Haller DG, Lockhart AC, Rocha Lima CM, Huang X, DePrimo SE, Chow-Maneval E, Chao RC, Lenz HJ (2007) Phase II trial of sunitinib in patients with metastatic colorectal cancer after failure of standard therapy. J Clin Oncol 25:4793-4799 (Pubitemid 350086483)
43. Fuchs CS, Tabernero JM, Hwang J, Bajetta E, Sharma S, DelPrete SA, Arrowsmith ER, Ryan DP, Hoosen S Multicenter phase II study of RAD001 in patients with chemotherapyrefractory metastatic colorectal cancer (mCRC). 2009 Gastrointestinal Cancers Symposium abstr 446
44. Townsley CA, Major P, Siu LL, Dancey J, Chen E, Pond GR, Nicklee T, Ho J, Hedley D, Tsao M, Moore MJ, Oza AM (2006) Phase II study of erlotinib (OSI-774) in patients with metastatic colorectal cancer. Br J Cancer 94:1136-1143
45. Bullock KE, Hurwitz HI, Uronis HE, Morse MA, Blobe GC, Hsu SD, Zafar SY, Nixon AB, Howard LA, Bendell JC (2009) Bevacizumab (B) plus everolimus (E) in refractory metastatic colorectal cancer (mCRC). J Clin Oncol 27:15S abstr 4080
46. Kovarik JM, Hartmann S, Hubert M, Berthier S, Schneider W, Rosenkranz B, Rordorf C (2002) Pharmacokinetic and pharmacodynamic assessments of HMG-CoA reductase inhibitors when coadministered with everolimus. J Clin Pharmacol 42:222-228 (Pubitemid 34101356)
47. Ling J, Johnson KA, Miao Z, Rakhit A, Pantze MP, Hamilton M, Lum BL, Prakash C (2006) Metabolism and excretion of erlotinib, a small molecule inhibitor of epidermal growth factor receptor tyrosine kinase, in healthy male volunteers. Drug metabolism and disposition: the biological fate of chemicals 34:420-426 (Pubitemid 43290900)
48. Zevin S, Benowitz NL (1999) Drug interactions with tobacco smoking. An update. Clinical pharmacokinetics 36:425-438 (Pubitemid 29317490)
49. Li J, Zhao M, He P, Hidalgo M, Baker SD (2007) Differential metabolism of gefitinib and erlotinib by human cytochrome P450 enzymes. Clin Cancer Res 13:3731-3737 (Pubitemid 46955138)
50. OSI Pharmaceuticals I, Genentech Inc., F. Hoffman-La Roche Ltd (2007) Tarceva Investigator's Brochure