Transcatheter embolization therapy in liver cancer

Recent Patents on Medical Imaging

Volumn 2, Issue 2, 2012, Pages 150-162

  Wang, Yi Xiang J ^a  

^a and Hong Kong Branch of CAS Center for Excellence in Animal Evolution and Genetics   (China)

Author keywords

Chemoembolization; Drug eluting particles; Hepatocellular carcinoma; Lipiodol; Microspheres; Radioembolization; Transarterial; Yttrium 90

Indexed keywords

ANTINEOPLASTIC AGENT; BLEOMYCIN; CISPLATIN; DOXORUBICIN; EMBOSPHERE; EMBOZENE; EPIRUBICIN; FLUOROURACIL; GELATIN SPONGE; HEMOSTATIC AGENT; IODINATED POPPYSEED OIL; IRINOTECAN; LIPIODOL ULTRA FLUID; MITOMYCIN; MITOXANTRONE; PIRARUBICIN; POLYVINYL ALCOHOL; RHENIUM 188; STARCH MICROSPHERE; TAMOXIFEN; UNCLASSIFIED DRUG; YTTRIUM 90; ZINOSTATIN; ZINOSTATIN MALEIC ACID STYRENE COPOLYMER;

ABDOMINAL PAIN; ARTERIOGRAPHY; ARTICLE; ARTIFICIAL EMBOLISM; BILE DUCT CARCINOMA; BIODEGRADABILITY; CATHETER; CHEMOEMBOLIZATION; CHOLECYSTITIS; COLORECTAL CANCER; DRUG DELIVERY DEVICE; DRUG DELIVERY SYSTEM; DRUG EFFICACY; DRUG SAFETY; EXTERNAL BEAM RADIOTHERAPY; FEVER; GASTROINTESTINAL DISEASE; GUIDE WIRE; HUMAN; HYDROPHILICITY; LIVER ABSCESS; LIVER CELL CARCINOMA; LIVER FAILURE; LIVER FUNCTION; LIVER FUNCTION TEST; LIVER METASTASIS; NATURAL KILLER CELL; PATENT; PORTAL VEIN; PRACTICE GUIDELINE; PRIORITY JOURNAL; SURVIVAL RATE; T LYMPHOCYTE; TUMOR RECURRENCE;

EID: 84870259018     PISSN: None     EISSN: 18776132     Source Type: Journal    
DOI: 10.2174/1877613211202020150     Document Type: Article

References (106)

1. Parkin DM, Bray F, Ferlay J, Pisani P. Estimating the world cancer burden: Globocan 2000. Int J Cancer 2001; 94: 153-156.
2. Adam R, Lucidi V, Bismuth H. Hepatic colorectal metastases: Methods of improving resectability. Surg Clin North Am 2004; 84: 659-671.
3. Meza-Junco J, Montano-Loza AJ, Liu DM, et al. Locoregional radiological treatment for hepatocellular carcinoma; Which, when and how? Cancer Treat Rev 2012; 38: 54-62.
4. Yamada R, Sato M, Kawabata M, Nakatsuka H, Nakamura K, Takashima S. Hepatic artery embolization in 120 patients with unresectable hepatoma. Radiology 1983; 148: 397-401.
5. Yamada R, Nakatsuka H, Nakamura K, et al. Hepatic artery embolization in 32 patients with unresectable hepatoma. Osaka City Med J 1980; 26: 81-96.
6. Brown DB, Gould JE, Gervais DA, et al. Transcatheter therapy for hepatic malignancy: Standardization of terminology and reporting criteria. J Vasc Interv Radiol 2007; 18: 1469-1478.
7. Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology 2005; 42: 1208-1236.
8. Bruix J, Sherman M, Llovet JM, et al. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. J Hepatol 2001; 35: 421-430.
9. Kudo M, Okanoue T. Management of hepatocellular carcinoma in Japan: Consensus-based clinical practice manual proposed by the Japan Society of Hepatology. Oncology 2007; 72: 2-15.
10. Breedis C, Young G. The blood supply of neoplasms in the liver. Am J Pathol 1954; 30: 969-985.
11. Nakashima T, Kojiro M. Pathologic characteristics of hepatocellular carcinoma. Semin Liver Dis 1986; 6: 259-266.
12. Vogl TJ, Naguib NN, Nour-Eldin NE, et al. Review on transarterial chemoembolization in hepatocellular carcinoma: Palliative, combined, neoadjuvant, bridging, and symptomatic indications. Eur J Radiol 2009; 72: 505-516.
13. Kleinstreuer C. Methods and devices for targeted injection of microspheres. US2010043552, 2010.
14. Lee JH, Won JH, Park SI, Won JY, Lee do Y, Kang BC. Transcatheter arterial chemoembolization of hepatocellularcarcinoma with hepatic arteriovenous shunt after temporary balloon occlusion of hepatic vein. J Vasc Interv Radiol 2007; 18: 377-382.
15. Shin SW. The current practice of transarterial chemoembolization for the treatment of hepatocellular carcinoma. Korean J Radiol 2009; 10: 425-434.
16. Park SH, Cho YK, Ahn YS, Park YO, Kim JK, Chung JW. Local recurrence of hepatocellular carcinoma after segmental transarterial chemoembolization: Risk estimates based on multiple prognostic factors. Korean J Radiol 2007; 8: 111-119.
17. Llovet JM, Sala M, Castells L, et al. Randomised controlled trial of interferon treatment for advanced hepatocellular carcinoma. Hepatology 2000; 31: 54-58.
18. Kruskal JB, Hlatky L, Hahnfeldt P, Teramoto K, Stokes KR, Clouse ME. In vivo and in vitro analysis of the effectiveness of doxorubicin combined with temporary arterial occlusion in liver tumors. J Vasc Interv Radiol 1993; 4: 741-747.
19. Lo CM, Ngan H, Tso WK, et al. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology 2002; 35: 1164-1171.
20. Camma C, Schepis F, Orlando A, et al. Transarterial chemoembolization for unresectable hepatocellular carcinoma: Meta-analysis of randomized controlled trials. Radiology 2002; 224: 47-54.
21. Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: Chemoembolization improves survival. Hepatology 2003; 37: 429-442.
22. Marelli L, Stigliano R, Triantos C, et al. Transarterial therapy for hepatocellular carcinoma: Which technique is more effective? A systematic review of cohort and randomized studies. Cardiovasc Intervent Radiol 2007; 30: 6-25.
23. Llovet JM, Di Bisceglie AM, Bruix J, et al. Panel of experts in HCC-design clinical trials design and endpoints of clinical trials in hepatocellular carcinoma. J Natl Cancer Inst 2008; 100: 698-711.
24. O'Suilleabhain CB, Poon RTP, Yong JL, Ooi GC, Tso WK, Fan ST. Factors predictive of 5-year survival after transarterial chemoembolization for inoperable hepatocellular carcinoma. Br J Surg 2003; 90: 325-331.
25. Gerundi GE, Neri D, Merenda R, et al. Role of transarterial chemoembolization before liver resection for hepatocarcinoma. Liver Transpl 2000; 6: 619-626.
26. Cho WC, Chen HY. Transcatheter arterial chemoembolization combined with or without Chinese herbal therapy for hepatocellular carcinoma: Meta-analysis. Expert Opin Invest Drugs 2009; 18: 617-635.
27. Yu Y, Lang Q, Chen Z, et al. The efficacy for unresectable hepatocellular carcinoma may be improved by transcatheter arterial chemoembolization in combination with a traditional Chinese herbal medicine formula: A retrospective study. Cancer 2009; 115: 5132-5138.
28. Tellez C, Benson AB, Lyster MT, et al. Phase II trial of chemoembolization for the treatment of metastatic colorectal carcinoma to the liver and review of the literature. Cancer 1998; 82: 1250-1259.
29. Geschwind J, Hong K, Georgiades C. Utility of transcatheter arterial chemoembolization for liver dominant colorectal metastatic adenocarcinoma in the salvage setting. Presented at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium. San Francisco, USA, January 26-28, 2006.
30. Burger I, Hong K, Schulick R, et al. Transcatheter arterial chemoembolization in unresectable cholangiocarcinoma: Initial experience in a single institution. J Vasc Interv Radiol 2005; 16: 353-361.
31. Vogl TJ, Gruber T, Naguib NN, Hammerstingl R, Nour-Eldin NE. Liver metastases of neuroendocrine tumors: Treatment with hepatic transarterial chemotherapy using two therapeutic protocols. Am J Roentgenol 2009; 193: 941-947.
32. Giroux MF, Baum RA, Soulen MC. Chemoembolization of liver metastasis from breast carcinoma. J Vasc Interv Radiol 2004; 15: 289-291.
33. Rajan DK, Soulen MC, Clark TW, et al. Sarcomas metastatic to the liver: Response and survival after Cisplatin, Doxorubicin, Mitomycin-C, Ethiodol, and Polyvinyl Alcohol chemoembolization. J Vasc Interv Radiol 2001; 12: 187-193.
34. Hellman S, Weichselbaum RR. Oligometastases. J Clin Oncol 1995; 13: 8-10.
35. Niibe Y, Hayakawa K. Oligometastases and oligo-recurrence: The new era of cancer therapy. Jpn J Clin Oncol 2010; 40: 107-111.
36. Bastian P, Bartkowski R, Kohler H, Kissel T. Chemo-embolization of experimental liver metastases. Part I: Distribution of biodegradable microspheres of different sizes in an animal model for the locoregional therapy. Eur J Pharm Biopharm 1998; 46: 243-254.
37. Choe DH, Han MH, Kang GH, Yeon KM, Han MC. An experimental study of embolic effect according to infusion rate and concentration of suspension in transarterial particulate embolization. Invest Radiol 1997; 32: 260-267.
38. Siskin GP, Dowling K, Virmani R, Jones R, Todd D. Pathologic evaluation of a spherical Polyvinyl Alcohol embolic agent in a porcine renal model. J Vasc Interv Radiol 2003; 14: 89-98.
39. Lopez-Benitez R, Richter GM, Kauczor HU, et al. Analysis of nontarget embolization mechanisms during embolization and chemoembolization procedures. Cardiovasc Intervent Radiol 2009; 32: 615-622.
40. Llovet JM, Real MI, Montana X, et al. Arterial embolization or chemoembolization versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: A randomised controlled trial. Lancet 2002; 359: 1734-1739.
41. Doppman JL, Dunnick NR, Girton M, Fauci AS, Popovsky MA. Bile duct cysts secondary to liver infarcts: Report of a case and experimental production by small vessel hepatic artery occlusion. Radiology 1979; 130: 1-5.
42. Makuuchi M, Sukigara M, Mori T, et al. Bile duct necrosis: Complication of transcatheter hepatic arterial embolization. Radiology 1985; 156: 331-334.
43. Nakamura H, Tanaka T, Hori S, et al. Transcatheter embolization of hepatocellular carcinoma: Assessment of efficacy in cases of resection following embolization. Radiology 1983; 147: 401-405.
44. Kettenbach J, Stadler A, Katzler IV, et al. Drug-loaded microspheres for the treatment of liver cancer: Review of current results. Cardiovasc Intervent Radiol 2008; 31: 468-476.
45. Coldwell DM, Stokes KR, Yakes WF. Embolotherapy: Agents, clinical applications, and techniques. Radiographics 1994; 14: 623-643.
46. Brown DB, Pilgram TK, Darcy MD, et al. Hepatic arterial chemoembolization for hepatocellular carcinoma: Comparison of survival rates with different embolic agents. J Vasc Interv Radiol 2005; 16: 1661-1666.
47. Rand T, Loewe C, Schoder M, et al. Arterial embolization of unresectable hepatocellular carcinoma with use of microspheres, Lipiodol, and Cyanoacrylate. Cardiovasc Intervent Radiol 2005; 28: 313-318.
48. Georgiades CS, Hong K, D'Angelo M, Geschwind JF. Safety and efficacy of transarterial chemoembolization in patients with unresectable hepatocellular carcinoma and portal vein thrombosis. J Vasc Interv Radiol 2005; 16: 1653-1659.
49. Bonomo G, Pedicini V, Monfardini L, et al. Bland embolization in patients with unresectable hepatocellular carcinoma using precise, tightly size-calibrated, anti-inflammatory microparticles: First clinical experience and one-year follow-up. Cardiovasc Intervent Radiol 2010; 33: 552-559.
50. Vogl TJ, Zangos S, Eichler K, Yakoub D, Nabil M. Colorectal liver metastases: Regional chemotherapy via transarterial chemoembolization (TACE) and hepatic chemoperfusion: An update. Eur Radiol 2007; 17: 1025-1034.
51. Kirchhoff TD, Bleck JS, Dettmer A, et al. Transarterial chemoembolization using degradable starch microspheres and iodized oil in the treatment of advanced hepatocellular carcinoma: Evaluation of tumor response, toxicity, and survival. Hepatobiliary Pancreat Dis Int 2007; 6: 259-266.
52. Li S, Dynan WS, Wicks G, Serkiz S. Porous-wall hollow glass microspheres as carriers for biomolecules. US2010042117, 2010.
53. Weng L, Golzarian J. Bioresorbable embolization microspheres. US2010051629, 2010.
54. Rolland PH, Vidal V, Bartoli JM, Levrier O, Choux C. Embolic material, its process of preparation and its therapeutical uses thereof. EP2353624A1, 2011.
55. Krom J, Reb P, Marion P, De Gioannis B. Microspheres useful for the therapeutic vascular embolization. EP051059, 2011.
56. Kanematsu T, Inokuchi K, Sugimachi K, et al. Selective effects of Lipiodolized antitumor agents. J Surg Oncol 1984; 25: 218-226.
57. Nakamura H, Hashimoto T, Oi H, Sawada S. Transcatheter oily chemoembolization of hepatocellular carcinoma. Radiology 1989; 170: 783-786.
58. Kim JH, Chung JW, Han JK, Park JH, Choi BI, Han MC. Transcatheter arterial embolization of the internal mammary artery in hepatocellular carcinoma. J Vasc Interv Radiol 1995; 6: 71-74.
59. Favoulet P, Cercueil JP, Faure P, et al. Increased cytotoxicity and stability of Lipiodol-Pirarubicin emulsion compared to classical Doxorubicin-Lipiodol: Potential advantage for chemoembolization of unresectable hepatocellular carcinoma. Anticancer Drugs 2001; 12: 801-806.
60. Okusaka T, Kasugai H, Ishii H. A randomized phase II trial of intra-arterial chemotherapy using a novel Lipophilic platinum derivative (SM-11355) in comparison with Zinostatin Stimalamer in patents with hepatocellular carcinoma. J Clin Oncol 2009; 27: 15s.
61. Hong K, Khwaja A, Liapi E, Torbenson MS, Georgiades CS, Geschwind JF. New intra-arterial drug delivery system for the treatment of liver cancer: Preclinical assessment in a rabbit model of liver cancer. Clin Cancer Res 2006; 12: 2563-2567.
62. Varela M, Real MI, Brunet M, et al. Chemoembolization of hepatocellular carcinoma with drug eluting beads: Efficacy and Doxorubicin pharmacokinetics. J Hepatol 2007; 46: 474-481.
63. Malagari K, Pomoni M, Kelekis A, et al. Prospective randomized comparison of chemoembolization with Doxorubicin-eluting beads and bland embolization with BeadBlock for hepatocellular carcinoma. Cardiovasc Intervent Radiol 2010; 33: 541-551.
64. Lammer J, Malagari K, Vogl T, et al. On behalf of the PRECISION V investigators prospective randomized study of Doxorubicineluting- bead embolization in the treatment of hepatocellular carcinoma: Results of the PRECISION V study. Cardiovasc Intervent Radiol 2010; 33: 41-52.
65. Vogl TJ, Lee C, Lencioni R, et al. Liver, gastrointestinal, and cardiac toxicity in intermediate hepatocellular carcinoma treated with PRECISION TACE with drug-eluting beads: Results from the PRECISION V randomized trial. J Clin Oncol 2010; 28: 14660A.
66. Malagari K. Drug-eluting particles in the treatment of HCC: Chemoembolization with Doxorubicin-loaded DC Bead (TM). Expert Rev Anticancer Ther 2008; 8: 1643-1650.
67. Sadick M, Haas S, Loehr M, et al. Application of DC beads in hepatocellular carcinoma: Clinical and radiological results of a drug delivery device for transcatheter superselective arterial embolization. Onkologie 2010; 33: 31-37.
68. Lewis AL, Gonzalez MV, Leppard SW, et al. Doxorubicin eluting beads-1: Effects of drug loading on bead characteristics and drug distribution. J Mater Sci Mater Med 2007; 18: 1691-1699.
69. Lewis AL, Gonzalez MV, Lloyd AW, et al. DC bead: In vitro characterization of a drug-delivery device for transarterial chemoembolization. J Vasc Interv Radiol 2006; 17: 335-342.
70. Gonzalez MV, Tang Y, Phillips GJ, et al. Doxorubicin eluting beads-2: Methods for evaluating drug elution and in-vitro: In-vivo correlation. J Mater Sci Mater Med 2008; 19: 767-775.
71. Osuga K, Khankan AA, Hori S, et al. Transarterial embolization for large hepatocellular carcinoma with use of superabsorbent polymer microspheres: Initial experience. J Vasc Interv Radiol 2002; 13: 929-934.
72. Grosso M, Vignali C, Quaretti P, et al. Transarterial chemoembolization for hepatocellular carcinoma with drug-eluting microspheres: Preliminary results from an Italian multicentre study. Cardiovasc Intervent Radiol 2008; 31: 1141-1149.
73. Bartlett DL, Berlin J, Lauwers GY, Messersmith WA, Petrelli NJ, Venook AP. Chemotherapy and regional therapy of hepatic colorectal metastases: Expert consensus statement. Ann Surg Oncol 2006; 13: 1284-1292.
74. Tang Y, Taylor RR, Gonzalez MV, Lewis AL, Stratford PW. Evaluation of Irinotecan drug-eluting beads: A new drug-device combination product for the chemoembolization of hepatic metastases. J Control Release 2006; 116: e55-e56.
75. Taylor RR, Tang YQ, Gonzalez MV, Stratford PW, Lewis AL. Irinotecan drug eluting beads for use in chemoembolization: In vitro and in vivo evaluation of drug release properties. Eur J Pharm Sci 2007; 30: 7-14.
76. Haaga JR, Exner AA, Wang Y, Stowe NT, Tarcha PJ. Combined tumor therapy by using radiofrequency ablation and 5-FU-laden polymer implants: Evaluation in rats and rabbits. Radiology 2005; 237: 911-918.
77. Lewis AL, Taylor RR, Hall B, Gonzalez MV, Willis SL, Stratford PW. Pharmacokinetic and safety study of Doxorubicin-eluting beads in a porcine model of hepatic arterial embolization. J Vasc Interv Radiol 2006; 17: 1335-1343.
78. Weinberg BD, Blanco E, Gao J. Polymer implants for intratumoral drug delivery and cancer therapy. J Pharm Sci 2008; 97: 1681-1702.
79. Ibrahim SM, Lewandowski RJ, Sato KT, et al. Radioembolization for the treatment of unresectable hepatocellular carcinoma: A clinical review. World J Gastroenterol 2008; 14: 1664-1669.
80. Salem R, Lewandowski RJ, Mulcahy MF, et al. Radioembolization for hepatocellular carcinoma using Yttrium-90 microspheres: A comprehensive report of long-term outcomes. Gastroenterology 2010; 138: 52-64.
81. Kulik LM, Carr BI, Mulcahy MF, et al. Safety and efficacy of 90Y radiotherapy for hepatocellular carcinoma with and without portal vein thrombosis. Hepatology 2008; 47: 71-81.
82. Raoul JL, Guyader D, Bretagne JF, et al. Prospective randomized trial of chemoembolization versus intra-arterial injection of 131Ilabeled- iodized oil in the treatment of hepatocellular carcinoma. Hepatology 1997; 26: 1156-1161.
83. Salem R, Lewandowski RJ, Kulik L, et al. Radioembolization results in longer time-to-progression and reduced toxicity compared with chemoembolization in patients with hepatocellular carcinoma. Gastroenterology 2011; 140: 497-507.
84. Gulec SA, Mesoloras G, Dezarn WA, McNeillie P, Kennedy AS. Safety and efficacy of Y-90 microsphere treatment in patients with primary and metastatic liver cancer: The tumor selectivity of the treatment as a function of tumor to liver flow ratio. J Transl Med 2007; 5: 15.
85. Salem R, Riaz A, Lewandowski R, Kulik L, Abecassis M, Mulcahy MF. Comparative effectiveness of radioembolization and the standard of care for hepatocellular carcinoma: Is a randomized survival study feasible? J Clin Oncol 2010; 28: 4045A.
86. Salem R, Thurston KG. Radioembolization with 90Yttrium microspheres: A state-of-the-art brachytherapy treatment for primary and secondary liver malignancies: Part 1: Technical and methodologic considerations. J Vasc Interv Radiol 2006; 17: 1251-1278.
87. Kumar A, Srivastava DN, Chau TT, et al. Inoperable hepatocellular carcinoma: Transarterial 188Re HDD-labeled iodized oil for treatment - Prospective multicenter clinical trial. Radiology 2007; 243: 509-519.
88. Peng YB, Lei XC. Particulate materials and compositions for radio therapy. US2005007201, 2005.
89. Noiret N, Garin E, Lepareur N, Ardisson V. Composition for treating liver cancer in humans based on Rhenium-188 and method for preparing such a composition. EP052420, 2011.
90. Bernal P, Raoul JL, Vidmar G, et al. Intra-arterial rhenium-188 Lipiodol in the treatment of inoperable hepatocellular carcinoma: Results of an IAEA-sponsored multination study. Int J Radiat Oncol Biol Phys 2007; 69: 1448-1455.
91. Iñarrairaegui M, Thurston KG, Bilbao JI, et al. Radioembolization with use of Yttrium-90 resin microspheres in patients with hepatocellular carcinoma and portal vein thrombosis. J Vasc Interv Radiol 2010; 21: 1205-1212.
92. Bartling S, Margel S, Aviv H. Multimodal visible polymer embolization material. EP059631, 2010.
93. Rioux RF, Casey TV, Lanphere JL. Embolization. US8012454, 2011.
94. Wang YX, Hussain SM, Krestin GP. Superparamagnetic iron oxide contrast agents: Physiochemical characteristics and applications in MR imaging. Eur Radiol 2001; 11: 2319-2331.
95. Wang YX. Superparamagnetic iron oxide based MRI contrast agents: Current status of clinical application. Quant Imaging Med Surg 2011; 1: 35-40.
96. Kinoshita Y, Sugimoto M, Ishiguro T. Therapeutic for hepatic cancer. JP2009001249, 2009.
97. Ishiguro T, Sugimoto M, Kinoshita Y, et al. Anti-glypican 3 antibody as a potential antitumor agent for human liver cancer. Cancer Res 2008; 68: 9832-9838.
98. Stewart MW, Noujaim A, Hirsche BD, Person RH. Methods of treatment using vascular occlusion in combination therapies. US7947282, 2011.
99. Morrison DR, Mosier B. Externally triggered microcapsules. WO99059556, 1999.
100. Levy RJ, Chorny M, Muzykantov V, Hood E. Uniform field magnetization and targeting of therapeutic formulations. US20100260780, 2010.
101. Wang Y, Leung KCF, Qin L, Cheng CHK. Magnetic nanomaterials and methods for chemoembolization. US20110217379, 2011.
102. Zhu XM, Leung KCF, Wang DW, Lee SF, Wang YX. Superparamagnetic Iron Oxide nanoshell and PVA based chemoembolization system: a novel approach for drug delivery, magnetic targeting and MRI. Korean Congress of Radiology - Annual Meeting. Seoul, South Korea 2011.
103. Mazzaferro V, Regalia E, Doci R, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 1996; 334: 693-699.
104. Llovet JM, Ricci S, Mazzaferro VN, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008; 359: 378-390.
105. Cheng AL, Kang YK, Chen Z, et al. Efficacy and safety of Sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: A phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol 2009; 10: 25-34.
106. Tam KY, Leung KC, Wang YX. Chemoembolization agents for cancer treatment. Eur J Pharm Sci 2011; 44: 1-10.