Selected combination therapy with sorafenib: A review of clinical data and perspectives in advanced solid tumors

Oncologist

Volumn 13, Issue 8, 2008, Pages 845-858

  Dal Lago, Lissandra ^a   D'Hondt, Véronique ^a   Awada, Ahmad ^a  

^a JULES BORDET INSTITUTE   (Belgium)

Author keywords

Combination; Hepatocellular carcinoma; Renal cell carcinoma; Solid tumors; Sorafenib

Indexed keywords

7 ETHYL 10 HYDROXYCAMPTOTHECIN; ALPHA INTERFERON; BEVACIZUMAB; CAPECITABINE; CARBOPLATIN; CISPLATIN; DOCETAXEL; ESTROGEN RECEPTOR; FLUOROURACIL; GEMCITABINE; HYPOXIA INDUCIBLE FACTOR 1ALPHA; HYPOXIA INDUCIBLE FACTOR 2ALPHA; IMATINIB; INTERFERON; IRINOTECAN; MITOGEN ACTIVATED PROTEIN KINASE; NAVELBINE; OXALIPLATIN; PACLITAXEL; PERIFOSINE; PLACEBO; PLATELET DERIVED GROWTH FACTOR; RAF PROTEIN; RAS PROTEIN; SORAFENIB; STAT PROTEIN; TRANSFORMING GROWTH FACTOR ALPHA; TYROSINE KINASE RECEPTOR; UNINDEXED DRUG; VASCULOTROPIN;

ABDOMINAL PAIN; ADVANCED CANCER; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ANOREXIA; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; BLEEDING; BRAIN METASTASIS; BREAST CANCER; CANCER COMBINATION CHEMOTHERAPY; CHRONIC LEUKEMIA; CLINICAL TRIAL; COLORECTAL CANCER; DEHYDRATION; DIARRHEA; DRUG ANTAGONISM; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG FATALITY; DRUG HYPERSENSITIVITY; DRUG POTENTIATION; EMBOLISM; EOSINOPHILIC LEUKEMIA; ESOPHAGUS CANCER; FATIGUE; FEBRILE NEUTROPENIA; GASTROINTESTINAL HEMORRHAGE; GASTROINTESTINAL SYMPTOM; GENE MUTATION; GLIOBLASTOMA; HAND FOOT SYNDROME; HEADACHE; HUMAN; HYPERAMYLASEMIA; HYPERLIPASEMIA; HYPERTENSION; HYPOKALEMIA; HYPOMAGNESEMIA; HYPOPHOSPHATEMIA; INFECTION; KIDNEY CARCINOMA; LEUKOPENIA; LIVER CELL CARCINOMA; LOW DRUG DOSE; LUNG CANCER; LYMPHOCYTOPENIA; MELANOMA; MESOTHELIOMA; MONOTHERAPY; MORNING DOSAGE; MUCOSA INFLAMMATION; MULTIDRUG RESISTANCE; MULTIPLE CYCLE TREATMENT; NAUSEA; NEUROPATHY; NEUTROPENIA; ONCOGENE K RAS; OVARY CANCER; OVARY CARCINOMA; PANCREAS CANCER; PRIORITY JOURNAL; PROTEINURIA; RASH; REVIEW; SENSORY NEUROPATHY; SIDE EFFECT; SIGNAL TRANSDUCTION; SKIN EXFOLIATION; SKIN MANIFESTATION; SOLID TUMOR; STOMACH CANCER; STOMATITIS; THROMBOCYTOPENIA; THROMBOSIS; THYROID MEDULLARY CARCINOMA; THYROID PAPILLARY CARCINOMA; TREATMENT OUTCOME; TRIACYLGLYCEROL LIPASE BLOOD LEVEL; TUMOR VASCULARIZATION; VOMITING;

ANTINEOPLASTIC AGENTS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; BENZENESULFONATES; HUMANS; NEOPLASMS; PYRIDINES;

EID: 51049098909     PISSN: 10837159     EISSN: 1549490X     Source Type: Journal    
DOI: 10.1634/theoncologist.2007-0233     Document Type: Review

References (111)

1. Timar J, Csuka O, Orosz Z et al. Molecular pathology of tumor metastasis. I. Predictive pathology. Pathol Oncol Res 2001;7:217-230.
2. Jemal A, Murray T, Ward E et al. Cancer statistics, 2005. CA Cancer J Clin 2005;55:10-30.
3. Wilhelm SM, Carter C, Tang L et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res 2004;64:7099-7109.
4. Davies H, Bignell GR, Cox C et al. Mutations of the BRAF gene in human cancer. Nature 2002;417:949-954.
5. Alavi A, Hood JD, Frausto R et al. Role of Raf in vascular protection from distinct apoptotic stimuli. Science 2003;301:94-96.
6. Odabaei G, Chatterjee D, Jazirehi AR et al. Raf-1 kinase inhibitor protein: Structure, function, regulation of cell signaling, and pivotal role in apoptosis. Adv Cancer Res 2004;91:169-200.
7. Yu C, Rahmani M, Almenara J et al. Induction of apoptosis in human leukemia cells by the tyrosine kinase inhibitor adaphostin proceeds through a RAF-1/MEK/ERK- and AKT-dependent process. Oncogene 2004;23:1364-1376.
8. Panka DJ, Wang W, Atkins MB et al. The Raf inhibitor BAY 43-9006 (sorafenib) induces caspase-independent apoptosis in melanoma cells. Cancer Res 2006;66:1611-1619.
9. Rahmani M, Davis EM, Bauer C et al. Apoptosis induced by the kinase inhibitor BAY 43-9006 in human leukemia cells involves down-regulation of Mcl-1 through inhibition of translation. J Biol Chem 2005;280:35217-35227.
10. Levy AP, Pauloski N, Braun D et al. Analysis of transcription and protein expression changes in the 786-O human renal cell carcinoma tumor xenograft model in response to treatment with the multi-kinase inhibitor sorafenib (BAY 43-9006) [abstract]. Proc Am Assoc Cancer Res 2006;47:213.
11. Hood JD, Bednarski M, Frausto R et al. Tumor regression by targeted gene delivery to the neovasculature. Science 2002;296:2404-2407.
12. Lee JT, McCubrey JA. BAY-43-9006 Bayer/Onyx. Curr Opin Investig Drugs 2003;4:757-763.
13. Sharma A, Trivedi NR, Zimmerman MA et al. Mutant V599EB-Raf regulates growth and vascular development of malignant melanoma tumors. Cancer Res 2005;65:2412-2421.
14. Chang YS, Henderson A, Xue D et al. BAY 43-9006 (sorafenib) inhibits ectopic and orthotopic growth of a murine model of renal adenocarcinoma (Renca) predominantly through inhibition of tumor angiogenesis [abstract]. Clin Cancer Res 2005;46:5831.
15. Yu C, Bruzek LM, Kaufmann SH et al. The raf kinase inhibitor BAY 43-9006 accelerates Mcl-1 degradation and regulates pro-apoptotic function. Clin Cancer Res 2005;46:6155.
16. Yu C, Bruzek LM, Meng XW et al. The role of Mcl-1 downregulation in the proapoptotic activity of the multikinase inhibitor BAY 43-9006. Oncogene 2005;24:6861-6869.
17. Ratain MJ, Flaherty KT, Stadler WM et al. Preliminary antitumor activity of BAY 43-9006 in metastatic renal cell carcinoma and other advanced refractory solid tumors in a phase II randomized discontinuation trial (RDT). J Clin Oncol 2004;22:381 (Abstract 4501; see also oral presentation at http://www.asco.org/).
18. Ratain MJ, Eisen T, Stadler WM et al. Phase II placebo-controlled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinoma. J Clin Oncol 2006;24:2505-2512.
19. Escudier B, Eisen T, Stadler WM et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 2007;356:125-134.
20. Lyons JF, Wilhelm S, Hibner B et al. Discovery of a novel Raf kinase inhibitor. Endocr Relat Cancer 2001;8:219-225.
21. Wilhelm S, Chien DS. BAY 43-9006: Preclinical data. Curr Pharm Des 2002;8:2255-2257.
22. Sridhar SS, Hedley D, Siu LL. Raf kinase as a target for anticancer therapeutics. Mol Cancer Ther 2005;4:677-685.
23. Ahmad T, Eisen T. Kinase inhibition with BAY 43-9006 in renal cell carcinoma. Clin Cancer Res 2004;10:6388S-6392S.
24. Lierman E, Folens C, Stover EH et al. Sorafenib is a potent inhibitor of FIP1L1-PDGFRα and the imatinib-resistant FIP1L1-PDGFRα T674I mutant. Blood 2006;108:1374-1376.
25. Carlomagno F, Anaganti S, Guida T et al. BAY 43-9006 inhibition of oncogenic RET mutants. J Natl Cancer Inst 2006;98:326-334.
26. Tang WY, Chau SP, Tsang WP et al. The role of Raf-1 in radiation resistance of human hepatocellular carcinoma Hep G2 cells. Oncol Rep 2004;12:1349-1354.
27. Vincent P, Zhang X, Chen C et al. Chemotherapy with the raf kinase inhibitor BAY 43-9006 in combination with irinotecan, vinorelbine, or gemcitabine is well tolerated and efficacious in preclinical xenograft models [abstract]. Proc Am Soc Clin Oncol 2002;21:23b.
28. Heim M, Sharifi M, Hilger RA et al. Antitumor effect and potentiation or reduction in cytotoxic drug activity in human colon carcinoma cells by the Raf kinase inhibitor (RKI) BAY 43-9006. Int J Clin Pharmacol Ther 2003;41:616-617.
29. Heim M, Scharifi M, Zisowsky J et al. The Raf kinase inhibitor BAY 43-9006 reduces cellular uptake of platinum compounds and cytotoxicity in human colorectal carcinoma cell lines. Anticancer Drugs 2005;16:129-136.
30. Nicol D, Hii SI, Walsh M et al. Vascular endothelial growth factor expression is increased in renal cell carcinoma. J Urol 1997;157:1482-1486.
31. Villegas G, Lange-Sperandio B, Tufro A. Autocrine and paracrine functions of vascular endothelial growth factor (VEGF) in renal tubular epithelial cells. Kidney Int 2005;67:449-457.
32. Ebbinghaus SW, Gordon MS. Renal cell carcinoma: Rationale and development of therapeutic inhibitors of angiogenesis. Hematol Oncol Clin North Am 2004;18:1143-1159, ix-x.
33. Strumberg D. Preclinical and clinical development of the oral multikinase inhibitor sorafenib in cancer treatment. Drugs Today (Barc) 2005;41:773-784.
34. NCT00126503: Sorafenib and Bevacizumab in Treating Patients With Advanced Kidney Cancer. Available at http://clinicaltrials.gov/ct2/results?term= NCT00126503. Accessed September 24, 2007.
35. Jonasch E, Corn P, Ashe RG et al. Randomized phase II study of sorafenib with or without low-dose IFN in patients with metastatic renal cell carcinoma [abstract]. J Clin Oncol 2007;25:260s.
36. Bracarda S, Porta C, Boni C et al. Randomized prospective phase II trial of two schedules of sorafenib daily and interferon-α2a (IFN) in metastatic renal cell carcinoma (RAPSODY): GOIRC Study 0681 [abstract]. J Clin Oncol 2007;25:255s.
37. NCT00121251: Sorafenib, Gemcitabine, and Capecitabine in Treating Patients With Unresectable and/or Metastatic Kidney Cancer. Available at http://clinicaltrials.gov/ct2/results?term=NCT00121251. Accessed September 24, 2007.
38. Stephenson J, Schreeder M, Waples J et al. Perifosine (P), active as a single agent for renal cell carcinoma (RCC), now in phase I trials combined with tyrosine kinase inhibitors (TKI) [abstract]. J Clin Oncol 2007;25:15622.
39. Karasarides M, Chiloeches A, Hayward R et al. B-RAF is a therapeutic target in melanoma. Oncogene 2004;23:6292-6298.
40. Streit M, Detmar M. Angiogenesis, lymphangiogenesis, and melanoma metastasis. Oncogene 2003;22:3172-3179.
41. Graells J, Vinyals A, Figueras A et al. Overproduction of VEGF concomitantly expressed with its receptors promotes growth and survival of melanoma cells through MAPK and PI3K signaling. J Invest Dermatol 2004;123:1151-1161.
42. Flaherty KT, Brose M, Schuchter L et al. Phase I/II trial of BAY 43-9006, carboplatin (C) and paclitaxel (P) demonstrates preliminary antitumor activity in the expansion cohort of patients with metastatic melanoma [abstract]. J Clin Oncol 2004;22:7507.
43. Agarwala SS, Keilholz U, Hogg D et al. Randomized phase III study of paclitaxel plus carboplatin with or without sorafenib as second-line treatment in patients with advanced melanoma [abstract]. J Clin Oncol 2007;25:8510.
44. NCT00110019: Carboplatin and Paclitaxel With or Without Sorafenib in Treating Patients With Unresectable Stage III or Stage IV Melanoma. Available at http://clinicaltrials.gov/ct2/results?term=NCT00110019. Accessed September 24, 2007.
45. Eisen T, Ahmad T, Marais R et al. Phase I trial of sorafenib (BAY 43-9006) combined with dacarbazine (DTIC) in patients with metastatic melanoma [abstract]. Eur J Cancer Suppl 2005;3:349.
46. Eisen T, Marais R, Affolter A et al. An open-label phase II study of sorafenib and dacarbazine as first-line therapy in patients with advanced melanoma [abstract]. J Clin Oncol 2007;25:8529.
47. Bedikian AY, Millward M, Pehamberger H et al. Bcl-2 Antisense (oblimersen sodium) plus dacarbazine in patients with advanced melanoma: The Oblimersen Melanoma Study Group. J Clin Oncol 2006;24:4738-4745.
48. McDermott DF, Sosman JA, Hodi FS et al. Randomized phase II study of dacarbazine with or without sorafenib in patients with advanced melanoma [abstract]. J Clin Oncol 2007;25:8511.
49. Azad NS, Annunziata C, Barrett T et al. Dual targeting of vascular endothelial growth factor (VEGF) with sorafenib and bevacizumab: Clinical and translational results [abstract]. J Clin Oncol 2007;25:3542.
50. Soria J, Lazar V, Lassau N et al. Sorafenib (S) and dacarbazine (D) combination in patients (pts) with advanced malignant solid tumors: Phase I study with tumor biopsy genomic analysis and dynamic contrast enhanced ultrasonography (DCE-US) [abstract]. J Clin Oncol 2007;25:3556.
51. Amaravadi R, Schuchter LM, McDermott DF et al. Updated results of a randomized phase II study comparing two schedules of temozolomide in combination with sorafenib in patients with advanced melanoma [abstract]. J Clin Oncol 2007;25:8527.
52. Park YN, Kim YB, Yang KM et al. Increased expression of vascular endothelial growth factor and angiogenesis in the early stage of multistep hepatocarcinogenesis. Arch Pathol Lab Med 2000;124:1061-1065.
53. Yamaguchi R, Yano H, Iemura A et al. Expression of vascular endothelial growth factor in human hepatocellular carcinoma. Hepatology 1998;28:68-77.
54. Llovet J, Ricci S, Mazzaferro V et al. Randomized phase III trial of sorafenib versus placebo in patients with advanced hepatocellular carcinoma (HCC) [abstract]. J Clin Oncol 2007;25:LBA1.
55. Richly H, Kupsch P, Passage K et al. Results of a phase I trial of BAY 43-9006 in combination with doxorubicin in patients with refractory solid tumors [abstract]. J Clin Oncol 2004;23:207.
56. Abou-Alfa GK, Schwartz L, Ricci S et al. Phase II study of BAY 43-9006 in patients with advanced hepatocellular carcinoma (HCC) [abstract]. Eur J Cancer 2004;2:16.
57. Richly H, Kupsch P, Passage K et al. Results of a phase I trial of BAY 43-9006 in combination with doxorubicin in patients with primary hepatic cancer. Ann Oncol 2004;15:iii104.
58. Bruix J, Sherman M, Llovet JM et al. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol 2001;35:421-430.
59. NCT00108953: A Research Study to Treat Patients With Advanced Hepatocellular Carcinoma. Available at http://clinicaltrials.gov/ct2/results? term=NCT00108953. Accessed September 24, 2007.
60. Ishino K, Fukazawa H, Shikano M et al. Enhancement of anchorage-independent growth of human pancreatic carcinoma MIA PaCa-2 cells by signaling from protein kinase C to mitogen-activated protein kinase. Mol Carcinog 2002;34:180-186.
61. Karayiannakis AJ, Bolanaki H, Syrigos KN et al. Serum vascular endothelial growth factor levels in pancreatic cancer patients correlate with advanced and metastatic disease and poor prognosis. Cancer Lett 2003;194:119-124.
62. Niedergethmann M, Rexin M, Hildenbrand R et al. Prognostic implications of routine, immunohistochemical, and molecular staging in resectable pancreatic adenocarcinoma. Am J Surg Pathol 2002;26:1578-1587.
63. Siu LL, Awada A, Takimoto CH et al. Phase I trial of sorafenib and gemcitabine in advanced solid tumors with an expanded cohort in advanced pancreatic cancer. Clin Cancer Res 2006;12:144-151.
64. Wallace JA, Locker G, Nattam S et al. Sorafenib (S) plus gemcitabine (G) for advanced pancreatic cancer (PC): A phase II trial of the University of Chicago Phase II Consortium [abstract]. J Clin Oncol 2007;25:4608.
65. NCT00114244: Sorafenib With or Without Gemcitabine in Treating Patients With Metastatic Pancreatic Cancer. Available at http://clinicaltrials.gov/ct2/ results?term=NCT00114244. Accessed September 24, 2007.
66. Singer G, Oldt R 3rd, Cohen Y et al. Mutations in BRAF and KRAS characterize the development of low-grade ovarian serous carcinoma. J Natl Cancer Inst 2003;95:484-486.
67. Nishida N, Yano H, Komai K et al. Vascular endothelial growth factor C and vascular endothelial growth factor receptor 2 are related closely to the prognosis of patients with ovarian carcinoma. Cancer 2004;101:1364-1374.
68. Welch S, Hirte H, Elit L et al. CA-125 response as a marker of clinical benefit in patients with recurrent ovarian cancer treated with gemcitabine and sorafenib - A trial of the PMH Phase II Consortium [abstract]. J Clin Oncol 2007;25:5519.
69. NCT00096200: Sorafenib With or Without Paclitaxel and Carboplatin in Treating Patients With Recurrent Ovarian Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer. Available at http://clinicaltrials.gov/ct2/results?term= NCT00096200. Accessed September 24, 2007.
70. Zhang H, Wu J, Meng L et al. Expression of vascular endothelial growth factor and its receptors KDR and Flt-1 in gastric cancer cells. World J Gastroenterol 2002;8:994-998.
71. Diaz-Rubio E. New chemotherapeutic advances in pancreatic, colorectal, and gastric cancers. The Oncologist 2004;9:282-294.
72. Vanhoefer U, Rougier P, Wilke H et al. Final results of a randomized phase III trial of sequential high-dose methotrexate, fluorouracil, and doxorubicin versus etoposide, leucovorin, and fluorouracil versus infusional fluorouracil and cisplatin in advanced gastric cancer: A trial of the European Organization for Research and Treatment of Cancer Gastrointestinal Tract Cancer Cooperative Group. J Clin Oncol 2000;18:2648-2657.
73. Kupsch P, Henning BF, Passarge K et al. Results of a phase I trial of sorafenib (BAY 43-9006) in combination with oxaliplatin in patients with refractory solid tumors, including colorectal cancer. Clin Colorectal Cancer 2005;5:188-196.
74. NCT00253370: Sorafenib, Docetaxel, and Cisplatin in Treating Patients With Metastatic or Locally Advanced Gastric or Gastroesophageal Junction Cancer That Cannot Be Removed by Surgery. Available at http://clinicaltrials.gov/ct2/ results?term=NCT00253370. Accessed September 24, 2007.
75. Siriwardana G, Bradford A, Coy D et al. Autocrine/paracrine regulation of breast cancer cell proliferation by growth hormone releasing hormone (GHRH) via Ras, Raf, and mitogen-activated protein kinase. Mol Endocrinol 2006;20:2010-2019.
76. Jacobs EJ, Feigelson HS, Bain EB et al. Polymorphisms in the vascular endothelial growth factor gene and breast cancer in the Cancer Prevention Study II cohort. Breast Cancer Res 2006;8:R22.
77. Awada A, Hendlisz A, Whenham N et al. Phase I trial to evaluate safety, pharmacokinetics, and efficacy of sorafenib combined with docetaxel in patients with advanced, refractory solid tumors [abstract]. Ann Oncol 2007;18:401.
78. NCT00217399: Sorafenib and Anastrozole in Treating Postmenopausal Women With Metastatic Breast Cancer. Available at http://clinicaltrials.gov/ct2/ results?term=NCT00217399. Accessed September 24, 2007.
79. Hong DS, Camacho L, Ng C et al. Phase I study of tipifarnib and sorafenib in patients with biopsiable advanced cancers (NCI protocol 7156 supported by NCI grant UO1 CA062461) [abstract]. J Clin Oncol 2007;25:3549.
80. Kerbel R, Folkman J. Clinical translation of angiogenesis inhibitors. Nat Rev Cancer 2002;2:727-739.
81. Chun HG, Waheed F, Iqbal A et al. A combination of capecitabine and thalidomide in patients with unresectable, recurrent or metastatic hepatocellular carcinoma [abstract]. Proc Am Soc Clin Oncol 2003;22:330.
82. Patt YZ, Hassan MM, Lozano RD et al. Phase II trial of systemic continuous fluorouracil and subcutaneous recombinant interferon Alfa-2b for treatment of hepatocellular carcinoma. J Clin Oncol 2003;21:421-427.
83. Mazzolini GD, Sangro B, Ruiz J et al. A Phase I clinical trial of intratumoral injection of adenovirus encoding interleukin-12 in patients with hepatocellular carcinoma and other advanced gastrointestinal tumors [abstract]. Presented at the 38th European Association for the Study of Liver (EASL) Annual Meeting, Geneva, Switzerland, July 3-6, 2003.
84. Lemoine NR, Hughes CM, Barton CM et al. The epidermal growth factor receptor in human pancreatic cancer. J Pathol 1992;166:7-12.
85. Xiong HQ, Abbruzzese JL. Epidermal growth factor receptor-targeted therapy for pancreatic cancer. Semin Oncol 2002;29(suppl 14):31-37.
86. Xiong HQ, Rosenberg A, LoBuglio A et al. Cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor, in combination with gemcitabine for advanced pancreatic cancer: A multicenter phase II trial. J Clin Oncol 2004;22:2610-2616.
87. Daikoku T, Wang D, Tranguch S et al. Cyclooxygenase-1 is a potential target for prevention and treatment of ovarian epithelial cancer. Cancer Res 2005;65:3735-3744.
88. Spinella F, Rosano L, Di Castro V et al. Inhibition of cyclooxygenase-1 and -2 expression by targeting the endothelin a receptor in human ovarian carcinoma cells. Clin Cancer Res 2004;10:4670-4679.
89. Munkarah AR, Genhai Z, Morris R et al. Inhibition of paclitaxel-induced apoptosis by the specific COX-2 inhibitor, NS398, in epithelial ovarian cancer cells. Gynecol Oncol 2003;88:429-433.
90. Jonjic N, Kovac K, Krasevic M et al. Epidermal growth factor-receptor expression correlates with tumor cell proliferation and prognosis in gastric cancer. Anticancer Res 1997;17:3883-3888.
91. Jung YD, Mansfield PF, Akagi M et al. Effects of combination antivascular endothelial growth factor receptor and anti-epidermal growth factor receptor therapies on the growth of gastric cancer in a nude mouse model. Eur J Cancer 2002;38:1133-1140.
92. Miller KD, Chap LI, Holmes FA et al. Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol 2005;23:792-799.
93. Ramaswamy B, Shapiro CL. Phase II trial of bevacizumab in combination with docetaxel in women with advanced breast cancer. Clin Breast Cancer 2003;4:292-294.
94. Burstein HJ, Parker LM, Savoie J et al. Phase II trial of the anti-VEGF antibody bevacizumab in combination with vinorelbine for refractory advanced breast cancer [abstract]. Breast Cancer Res Treat 2002;446.
95. Clark JW, Eder JP, Ryan D et al. Safety and pharmacokinetics of the dual action Raf kinase and vascular endothelial growth factor receptor inhibitor, BAY 43-9006, in patients with advanced, refractory solid tumors. Clin Cancer Res 2005;11:5472-5480.
96. Awada A, Hendlisz A, Gil T et al. Phase I safety and pharmacokinetics of BAY 43-9006 administered for 21 days on/7 days off in patients with advanced, refractory solid tumours. Br J Cancer 2005;92:1855-1861.
97. Moore M, Hirte HW, Siu L et al. Phase I study to determine the safety and pharmacokinetics of the novel Raf kinase and VEGFR inhibitor BAY 43-9006, administered for 28 days on/7 days off in patients with advanced, refractory solid tumors. Ann Oncol 2005;16:1688-1694.
98. Strumberg D, Richly H, Hilger RA et al. Phase I clinical and pharmacokinetic study of the novel Raf kinase and vascular endothelial growth factor receptor inhibitor BAY 43-9006 in patients with advanced refractory solid tumors. J Clin Oncol 2005;23:965-972.
99. Takimoto CH, Awada A. Safety and anti-tumor activity of sorafenib (Nexavar®) in combination with other anti-cancer agents: A review of clinical trials. Cancer Chemother Pharmacol 2008;61:535-548.
100. Strumberg D, Clark JW, Awada A et al. Safety, pharmacokinetics, and preliminary antitumor activity of sorafenib: A review of four phase I trials in patients with advanced refractory solid tumors. The Oncologist 2007;12:426-437.
101. Minasian LM, Motzer RJ, Gluck L et al. Interferon alfa-2a in advanced renal cell carcinoma: Treatment results and survival in 159 patients with long-term follow-up. J Clin Oncol 1993;11:1368-1375.
102. Jonasch E, Haluska FG. Interferon in oncological practice: Review of interferon biology, clinical applications, and toxicities. The Oncologist 2001;6:34-55.
103. Lee J, Park JO, Kim WS et al. Phase II study of doxorubicin and cisplatin in patients with metastatic hepatocellular carcinoma. Cancer Chemother Pharmacol 2004;54:385-390.
104. Yang TS, Lin YC, Chen JS et al. Phase II study of gemcitabine in patients with advanced hepatocellular carcinoma. Cancer 2000;89:750-756.
105. Brendel E, Zafarana E, Figuerola C et al. Pharmacokinetic results of a phase I trial of sorafenib (S) in combination with dacarbazine (DTIC) in patients with advanced metastatic melanoma or other solid tumors [abstract]. J Clin Oncol 2007;25:2563.
106. Awada A, Gil T, Whenham N et al. Phase I dose-escalation trial evaluating the safety and pharmacokinetics of sorafenib combined with capecitabine in patients with advanced solid tumors [abstract]. Ann Oncol 2007;18:402.
107. Mross K, Steinbild S, Baas F et al. Drug-drug interaction pharmacokinetic study with the Raf kinase inhibitor (RKI) BAY 43-9006 administered in combination with irinotecan (CPT-11) in patients with solid tumors. Int J Clin Pharmacol Ther 2003;41:618-619.
108. Lewis TS, Shapiro PS, Ahn NG. Signal transduction through MAP kinase cascades. Adv Cancer Res 1998;74:49-139.
109. Robinson MJ, Cobb MH. Mitogen-activated protein kinase pathways. Curr Opin Cell Biol 1997;9:180-186.
110. Gollob JA, Wilhelm S, Carter C et al. Role of Raf kinase in cancer: Therapeutic potential of targeting the Raf/MEK/ERK signal transduction pathway. Semin Oncol 2006;33:392-406.
111. Kolch W, Kotwaliwale A, Vass K et al. The role of Raf kinases in malignant transformation. Expert Rev Mol Med 2002;4:1-18.