Targeted approaches to childhood cancer: Progress in drug discovery and development

Expert Opinion on Drug Discovery

Volumn 10, Issue 5, 2015, Pages 483-495

  Hirsch, Steffen ^a,b   Marshall, Lynley V ^a,b   Carceller Lechon, Fernando ^a,b   Pearson, Andrew D J ^a,b   Moreno, Lucas ^a,b,c  

^a INSTITUTE OF CANCER RESEARCH   (United Kingdom)

^b INSTITUTE OF CANCER RESEARCH   (United Kingdom)

^c Structural Biology and Biocomputing Programme   (Spain)

Author keywords

Drug development; Oncology; Paediatric; Targeted therapy

Indexed keywords

4 (4 CHLOROPHENYL) N (4 HYDROXYPHENYL) 2,3,9 TRIMETHYL 6H THIENO[3,2 F][1,2,4]TRIAZOLO[4,3 A][1,4]DIAZEPINE 6 ACETAMIDE; 6 (4 CHLOROPHENYL) N ETHYL 8 METHOXY 1 METHYL 4H [1,2,4]TRIAZOLO[4,3 A][1,4]BENZODIAZEPINE 4 ACETAMIDE; ALECTINIB; ANAPLASTIC LYMPHOMA KINASE; ANTINEOPLASTIC AGENT; ASPARAGINASE; B RAF KINASE; BEVACIZUMAB; BIOLOGICAL MARKER; CEDIRANIB; CERITINIB; CILENGITIDE; CLOFARABINE; CRIZOTINIB; DABRAFENIB; MAMMALIAN TARGET OF RAPAMYCIN INHIBITOR; MITOGEN ACTIVATED PROTEIN KINASE; NEW DRUG; OLAPARIB; PANOBINOSTAT; PAZOPANIB; REGORAFENIB; SONIDEGIB; SORAFENIB; SUNITINIB; UNINDEXED DRUG; VELIPARIB; VEMURAFENIB; VISMODEGIB; VORINOSTAT; TUMOR MARKER;

BASAL CELL CARCINOMA; BREAST CANCER; CANCER CHEMOTHERAPY; CANCER PATIENT; CELL CYCLE REGULATION; CHILD; CHILDHOOD CANCER; CLINICAL RESEARCH; CLINICAL TRIAL (TOPIC); CONCEPTUAL FRAMEWORK; DEVELOPMENTAL TOXICITY; DNA REPAIR; DRUG DESIGN; DRUG EFFICACY; DRUG INDUSTRY; DRUG LEGISLATION; DRUG SAFETY; EPIGENETICS; EUROPE; GENE EXPRESSION; GLIOMA; HUMAN; IN VITRO STUDY; IN VIVO STUDY; INTERNATIONAL COOPERATION; KIDNEY CARCINOMA; LARGE CELL LYMPHOMA; LIVER CELL CARCINOMA; MELANOMA; MOLECULAR BIOLOGY; MOLECULARLY TARGETED THERAPY; NEOPLASM; NEUROBLASTOMA; NEUROBLASTOMA CELL; NON SMALL CELL LUNG CANCER; OVARY CARCINOMA; OVERALL SURVIVAL; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; SOLID TUMOR; AGE; ANIMAL; DRUG DEVELOPMENT; DRUG SCREENING; METABOLISM; NEOPLASMS; PATHOLOGY; PROCEDURES; SURVIVAL RATE;

AGE FACTORS; ANIMALS; ANTINEOPLASTIC AGENTS; BIOMARKERS, TUMOR; CHILD; DRUG DESIGN; DRUG DISCOVERY; DRUG EVALUATION, PRECLINICAL; HUMANS; MOLECULAR TARGETED THERAPY; NEOPLASMS; SURVIVAL RATE;

EID: 84928330055     PISSN: 17460441     EISSN: 1746045X     Source Type: Journal    
DOI: 10.1517/17460441.2015.1025745     Document Type: Review

References (102)

1. Ries L, Smith M, Gurney J, et al. Cancer Incidence and Survival among Children and Adolescents: United States SEER Program 1975-1995. Natl Cancer Inst 1999;NIH Pub:No. 99-4649
2. Smith MA, Altekruse SF, Adamson PC, et al. Declining childhood and adolescent cancer mortality. Cancer 2014;120:2497-506
3. Gatta G, Zigon G, Capocaccia R, et al. Survival of European children and young adults with cancer diagnosed 1995-2002. Eur J Cancer 2009;45:992-1005
4. Garrido-Laguna I, Hidalgo M, Kurzrock R. The inverted pyramid of biomarker-driven trials. Nat Rev Clin Oncol 2011;8:562-6
5. Yap T, Sandhu SK, Workman P, et al. Envisioning the future of early anticancer drug development. Nat Rev Cancer 2010;10:514-23
6. Shaddy RE, Denne SC. Clinical report-guidelines for the ethical conduct of studies to evaluate drugs in pediatric populations. Pediatrics 2010;125:850-60
7. Bautista F, Giannatale AD, Dias-Gastellier N, et al. Patients in pediatric phase I and early phase II clinical oncology trials at gustave roussy: a 13-year center experience. J Pediatr Hematol Oncol 2015;37:e102-10
8. Morgenstern D, Hargrave D, Marshall L V, et al. Toxicity and outcome of children and adolescents participating in phase I/II trials of novel anticancer drugs: the royal marsden experience. J Pediatr Hematol Oncol 2013;00:1-6
9. Adamson PC, Houghton PJ, Perilongo G, et al. Drug discovery in paediatric oncology: roadblocks to progress. Nat Rev Clin Oncol 2014;11:732-9
10. Pritchard-Jones K, Hargrave D. Declining childhood and adolescent cancer mortality: great progress but still much to be done. Cancer 2014;120:2388-91
11. Kowalczyk JR, Samardakiewicz M, Fitzgerald E, et al. Towards reducing inequalities: european Standards of Care for Children with Cancer. Eur J Cancer 2014;50:481-5
12. Pritchard-Jones K, Pieters R, Reaman GH, et al. Sustaining innovation and improvement in the treatment of childhood cancer: lessons from high-income countries. Lancet Oncol 2013;14:e95-e103
13. The pharmaceutical Research and Manufacturers of America-PhRMA. Cancer Report. 2014
14. Houghton PJ. New insights into drug development for pediatric solid tumors: what preclinical data justify clinical trials in pediatric cancer? Expert Rev Anticancer Ther 2013;13:1135-8
15. Vassal G, Rousseau R, Blanc P, et al. Creating a unique, multi-stakeholder Paediatric Oncology Platform to improve drug development for children and adolescents with cancer. Eur J Cancer 2015;51:218-24
16. Zwaan CM, Kearns P, Caron H, et al. The role of the "innovative therapies for children with cancer" (ITCC) European consortium. Cancer Treat Rev 2010;36:328-34
17. European Medicines Agency. Paediatric Regulation
18. European Medicines Agency, REGULATION (EC) No 1901/2006 on medicinal products for paediatric use. Available from: http://ec.europa.eu/health/files/eudralex/vol-1/reg-2006-1901/reg-2006-1901-en.pdf [last accessed 15 March 2015]
19. Vassal G. Will children with cancer benefit from the new European Paediatric Medicines Regulation? Eur J Cancer 2009;45:1535-46
20. Vassal G, Zwaan CM, Ashley D, et al. New drugs for children and adolescents with cancer: the need for novel development pathways. Lancet Oncol 2013;14:e117-24
21. Mullighan CG, Su X, Zhang J, et al. Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia. N Engl J Med 2009;360:470-80
22. Pugh TJ, Morozova O, Attiyeh EF, et al. The genetic landscape of high-risk neuroblastoma. Nat Genet 2013;45:279-84
23. Houghton PJ, Morton CL, Tucker C, et al. The pediatric preclinical testing program: description of models and early testing results. Pediatr Blood Cancer 2007;49:928-40
24. Lawrence M, Stojanov P, Polak P. Mutational heterogeneity in cancer and the search for new cancer genes. Nature 2013;499:214-18
25. Moreno L, Chesler L, Hargrave D, et al. Preclinical drug development for childhood cancer. Expert Opin Drug Discov 2011;6:49-64
26. Schleiermacher G, Janoueix-Lerosey I, Ribeiro A, et al. Accumulation of segmental alterations determines progression in neuroblastoma. J Clin Oncol 2010;28:3122-30
27. Carr-Wilkinson J, O'Toole K, Wood KM, et al. High Frequency of p53/MDM2/p14ARF Pathway Abnormalities in Relapsed Neuroblastoma. Clin Cancer Res 2010;16:1108-18
28. Chesler L, Goldenberg DD, Seales IT, et al. Malignant progression and blockade of angiogenesis in a murine transgenic model of neuroblastoma. Cancer Res 2007;67:9435-42
29. Lau J, Schmidt C, Markant SL, et al. Matching mice to malignancy: molecular subgroups and models of medulloblastoma. Childs Nerv Syst 2012;28:521-32
30. Paoletti X, Geoerger B, Doz F, et al. A comparative analysis of paediatric dose-finding trials of molecularly targeted agent with adults' trials. Eur J Cancer 2013;49:2392-402
31. Doussau A, Asselain B, Le Deley MC, et al. Dose-finding designs in pediatric phase I clinical trials: comparison by simulations in a realistic timeline framework. Contemp Clin Trials 2012;33:657-65
32. Bagatell R, Herzog CE, Trippett TM, et al. Pharmacokinetically guided phase 1 trial of the IGF-1 receptor antagonist RG1507 in children with recurrent or refractory solid tumors. Clin Cancer Res 2011;17:611-19
33. Geoerger B, Hargrave D, Thomas F, et al. Innovative Therapies for Children with Cancer pediatric phase I study of erlotinib in brainstem glioma and relapsing/refractory brain tumors. Neuro Oncol 2011;13:109-18
34. Mussai FJ, Yap C, Mitchell C, et al. Challenges of clinical trial design for targeted agents against pediatric leukemias. Front Oncol 2014;4:374
35. Kearns GL, Abdel-Rahman S, Alander SW, et al. Developmental pharmacology-drug disposition, action, and therapy in infants and children. N Engl J Med 2003;349(12):1157-67
36. Gore L, DeGregori J, Porter CC. Targeting developmental pathways in children with cancer: what price success? Lancet Oncol 2013;14:e70-8
37. Millot F, Claviez A, Leverger G, et al. Imatinib cessation in children and adolescents with chronic myeloid leukemia in chronic phase. Pediatr Blood Cancer 2014;61:355-7
38. Soda M, Choi YL, Enomoto M, et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 2007;448:561-6
39. Van Gaal JC, Flucke UE, Roeffen MHS, et al. Anaplastic lymphoma kinase aberrations in rhabdomyosarcoma: clinical and prognostic implications. J Clin Oncol 2012;30:308-15
40. Corao DA, Biegel JA, Coffin CM, et al. ALK expression in rhabdomyosarcomas: correlation with histologic subtype and fusion status. Pediatr Dev Pathol 2008;12:275-83
41. Steuer CE, Ramalingam SS. ALK-positive non-small cell lung cancer: mechanisms of resistance and emerging treatment options. Cancer 2014;120:2392-402
42. Gadgeel SM, Gandhi L, Riely GJ, et al. Safety and activity of alectinib against systemic disease and brain metastases in patients with crizotinib-resistant ALK-rearranged non-small-cell lung cancer (AF-002JG): results from the dose-finding portion of a phase 1/2 study. Lancet Oncol 2014;15:1119-28
43. De Brouwer S, De Preter K, Kumps C, et al. Meta-analysis of neuroblastomas reveals a skewed ALK mutation spectrum in tumors with MYCN amplification. Clin cancer Res 2010;16:4353-62
44. Mosse YP, Lim MS, Voss SD, et al. Safety and activity of crizotinib for paediatric patients with refractory solid tumours or anaplastic large-cell lymphoma: a Children's Oncology Group phase 1 consortium study. Lancet Oncol 2013;14:472-80
45. Bresler SC, Wood AC, Haglund EA, et al. Differential inhibitor sensitivity of anaplastic lymphoma kinase variants found in neuroblastoma. Sci Transl Med 2011;3:108ra114
46. Friboulet L, Li N, Katayama R, et al. The ALK inhibitor ceritinib overcomes crizotinib resistance in non-small cell lung cancer. Cancer Discov 2014;4:662-73
47. Berry T, Luther W, Bhatnagar N, et al. The ALK(F1174L) mutation potentiates the oncogenic activity of MYCN in neuroblastoma. Cancer Cell 2012;22:117-30
48. Kodama T, Tsukaguchi T, Yoshida M, et al. Selective ALK inhibitor alectinib with potent antitumor activity in models of crizotinib resistance. Cancer Lett 2014;351:215-21
49. Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature 2002;417:949-54
50. Daniotti M, Ferrari A, Frigerio S, et al. Cutaneous melanoma in childhood and adolescence shows frequent loss of INK4A and gain of KIT. J Invest Dermatol 2009;129:1759-68
51. Jones DTW, Kocialkowski S, Liu L, et al. Tandem duplication producing a novel oncogenic BRAF fusion gene defines the majority of pilocytic astrocytomas. Cancer Res 2008;68:8673-7
52. Sievert AJ, Lang S-S, Boucher KL, et al. Paradoxical activation and RAF inhibitor resistance of BRAF protein kinase fusions characterizing pediatric astrocytomas. Proc Natl Acad Sci USA 2013;110:5957-62
53. Kieran MW, Cohen KJ, Doz F, et al. Complete radiographic responses in pediatric patients with BRAFV600-positive tumors including high-grade gliomas: Preliminary results of an ongoing phase 1/2a safety and pharmacokinetics (PK) study of dabrafenib. J Clin Oncol 2014;32(Suppl):abstract 10056
54. Bautista F, Paci A, Minard-Colin V, et al. Vemurafenib in pediatric patients with BRAFV600E mutated high-grade gliomas. Pediatr Blood Cancer 2014;61:1101-3
55. Flaherty KT, Infante JR, Daud A, et al. Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. N Engl J Med 2012;367:1694-703
56. Widemann BC, Marcus LJ, Fisher MJ, et al. Phase I study of the MEK1/2 inhibitor selumetinib (AZD6244) hydrogen sulfate in children and young adults with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PNs). J Clin Oncol 2014;32(Suppl):abstract 10018
57. Irving J, Matheson E, Minto L, et al. Ras pathway mutations are prevalent in relapsed childhood acute lymphoblastic leukemia and confer sensitivity to MEK inhibition. Blood 2014;124:3420-30
58. 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;123:473-84
59. Gajjar A, Stewart CF, Ellison DW, et al. Phase I study of vismodegib in children with recurrent or refractory medulloblastoma: a pediatric brain tumor consortium study. Clin Cancer Res 2013;19:6305-12
60. Kieran MW, Geoerger B, Casanova M, et al. A phase 1/2 safety and preliminary efficacy study of sonidegib (LDE225), a Hedgehog pathway inhibitor, in pediatric and adult patients with relapsed or refractory medulloblastoma and other solid tumors-Abstract NO-068 [abstract NO-068]. Neuro Oncol 2013;15:iii115
61. Amakye D, Robinson D, Rose K, et al. The predictive value of a 5-gene signature as a patient pre-selection tool in medulloblastoma for Hedgehog pathway inhibitor therapy. Cancer Res 2012;72:abstract 4818
62. Kieran MW, Hargrave D, Wen PY, et al. A phase 3, multicenter, open-label, randomized, controlled study of the efficacy and safety of oral sonidegib (LDE225) versus temozolomide in patients with Hedgehog pathway-activated relapsed medulloblastoma [abstract NO-069]. Neuro Oncol 2013;15:iii115
63. Kieran M, Hargrave D. A phase 3, multicenter, open-label, randomized, controlled study of the efficacy and safety of oral sonidegib (LDE225) versus temozolomide in patients with Hedgehog pathway-activated relapsed medulloblastoma. Neuro Oncol 2013;15:115
64. Kimura H, Ng JMY, Curran T. Transient inhibition of the Hedgehog pathway in young mice causes permanent defects in bone structure. Cancer Cell 2008;13:249-60
65. Hu X, Zhang S, Chen G, et al. Expression of SHH signaling molecules in the developing human primary dentition. BMC Dev Biol 2013;13:11
66. Hanahan D, Weinberg R. The hallmarks of cancer. Cell 2000;100:57-70
67. Glade Bender JL, Adamson PC, Reid JM, et al. Phase I trial and pharmacokinetic study of bevacizumab in pediatric patients with refractory solid tumors: a Children's Oncology Group Study. J Clin Oncol 2008;26:399-405
68. Dubois SG, Shusterman S, Ingle AM, et al. Phase I and pharmacokinetic study of sunitinib in pediatric patients with refractory solid tumors: a children's oncology group study. Clin Cancer Res 2011;17:5113-22
69. Glade Bender JL, Lee A, Reid JM, et al. Phase I pharmacokinetic and pharmacodynamic study of pazopanib in children with soft tissue sarcoma and other refractory solid tumors: a children's oncology group phase I consortium report. J Clin Oncol 2013;31:3034-43
70. MacDonald TJ, Stewart CF, Kocak M, et al. Phase I clinical trial of cilengitide in children with refractory brain tumors: pediatric Brain Tumor Consortium Study PBTC-012. J Clin Oncol 2008;26:919-24
71. Fox E, Aplenc R, Bagatell R, et al. A phase 1 trial and pharmacokinetic study of cediranib, an orally bioavailable pan-vascular endothelial growth factor receptor inhibitor, in children and adolescents with refractory solid tumors. J Clin Oncol 2010;28:5174-81
72. Fangusaro J, Gururangan S, Poussaint TY, et al. Bevacizumab (BVZ)-associated toxicities in children with recurrent central nervous system tumors treated with BVZ and irinotecan (CPT-11): a Pediatric Brain Tumor Consortium Study (PBTC-022). Cancer 2013;119:4180-7
73. De Pasquale MD, Castellano A, De Sio L, et al. Bevacizumab in pediatric patients: how safe is it? Anticancer Res 2011;31:3953-7
74. Ryan AM, Eppler DB, Hagler KE, et al. Preclinical Safety Evaluation of rhuMAbVEGF, an Antiangiogenic Humanized Monoclonal Antibody. Toxicol Pathol 1999;27:78-86
75. Smith AR, Hennessy JM, Kurth MAH, et al. Reversible skeletal changes after treatment with bevacizumab in a child with cutaneovisceral angiomatosis with thrombocytopenia syndrome. Pediatr Blood Cancer 2008;51:418-20
76. Voss SD, Glade-Bender J, Spunt SL, et al. Growth plate abnormalities in pediatric cancer patients undergoing phase 1 anti-angiogenic therapy: a report from the children's oncology group phase I consortium. Pediatr Blood Cancer 2015;62:45-51
77. Delmore JE, Issa GC, Lemieux ME, et al. BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell 2011;146:904-17
78. Puissant A, Frumm SM, Alexe G, et al. Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov 2013;3:308-23
79. Schwartzentruber J, Korshunov A, Liu X-Y, et al. Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature 2012;482:226-31
80. Taylor KR, Mackay A, Truffaux N, et al. Recurrent activating ACVR1 mutations in diffuse intrinsic pontine glioma. Nat Genet 2014;46:457-61
81. Wu G, Diaz AK, Paugh BS, et al. The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma. Nat Genet 2014;46:444-50
82. Buczkowicz P, Bartels U, Bouffet E, et al. Histopathological spectrum of paediatric diffuse intrinsic pontine glioma: diagnostic and therapeutic implications. Acta Neuropathol 2014;128:573-81
83. Wang G, Edwards H, Caldwell JT, et al. Panobinostat synergistically enhances the cytotoxic effects of cisplatin, doxorubicin or etoposide on high-risk neuroblastoma cells. PLoS ONE 2013;8:e76662
84. Frumm SM, Fan ZP, Ross KN, et al. Selective HDAC1/HDAC2 inhibitors induce neuroblastoma differentiation. Chem Biol 2013;20:713-25
85. Milde T, Lodrini M, Savelyeva L, et al. HD-MB03 is a novel Group 3 medulloblastoma model demonstrating sensitivity to histone deacetylase inhibitor treatment. J Neurooncol 2012;110:335-48
86. Ecker J, Witt O, Milde T. Targeting of histone deacetylases in brain tumors. CNS Oncol 2013;2:359-76
87. Muscal JA, Scorsone KA, Zhang L, et al. Additive effects of vorinostat and MLN8237 in pediatric leukemia, medulloblastoma, and neuroblastoma cell lines. Invest New Drugs 2013;31:39-45
88. Masetti R, Serravalle S, Biagi C, et al. The role of HDACs inhibitors in childhood and adolescence acute leukemias. J Biomed Biotechnol 2011;2011:148046
89. Fouladi M, Park JR, Stewart CF, et al. Pediatric phase I trial and pharmacokinetic study of vorinostat: a Children's Oncology Group phase I consortium report. J Clin Oncol 2010;28:3623-9
90. Wood PJ, Strong R, Mcarthur GA, et al. A phase I study of panobinostat in pediatric patients with refractory solid tumors, including CNS tumors. J Clin Oncol 2014;32(Suppl):abstract 10061
91. Branzei D, Foiani M. Regulation of DNA repair throughout the cell cycle. Nat Rev Mol Cell Biol 2008;9:297-308
92. Norris RE, Adamson PC, Nguyen VT, et al. Preclinical evaluation of the PARP inhibitor, olaparib, in combination with cytotoxic chemotherapy in pediatric solid tumors. Pediatr Blood Cancer 2014;61:145-50
93. Handgretinger R, Anderson K, Lang P, et al. A phase I study of human/mouse chimeric antiganglioside GD2 antibody ch14.18 in patients with neuroblastoma. Eur J Cancer 1995;31A:261-7
94. Yu AL, Uttenreuther-Fischer MM, Huang CS, et al. Phase I trial of a human-mouse chimeric anti-disialoganglioside monoclonal antibody ch14.18 in patients with refractory neuroblastoma and osteosarcoma. J Clin Oncol 1998;16:2169-80
95. Ozkaynak BMF, Sondel PM, Krailo MD, et al. Phase I study of chimeric human/murine anti-ganglioside GD2 monoclonal antibody (ch14.18) with hematopoietic stem-cell transplantation: a children's cancer group study. J Clin Oncol 2000;18:4077-85
96. Hank JA, Robinson RR, Surfus J, et al. Augmentation of antibody dependent cell mediated cytotoxicity following in vivo therapy with recombinant interleukin 2 augmentation of antibody dependent cell mediated cytotoxicity following in vivo therapy with recombinant interleukin 21. Cancer Res 1990;50:5234-9
97. Gilman AL, Ozkaynak MF, Matthay KK, et al. Phase I study of ch14.18 with granulocyte-macrophage colony-stimulating factor and interleukin-2 in children with neuroblastoma after autologous bone marrow transplantation or stem-cell rescue: a report from the Children's Oncology Group. J Clin Oncol 2009;27:85-91
98. Cheung N-K, Cheung IY, Kushner BH, et al. Murine anti-GD2 monoclonal antibody 3F8 combined with granulocyte-macrophage colony-stimulating factor and 13-cis-retinoic acid in high-risk patients with stage 4 neuroblastoma in first remission. J Clin Oncol 2012;30:3264-70
99. Yu AL, Gilman AL, Ozkaynak MF, et al. Update of outcome for high-risk neuroblastoma treated on a randomized trial of chimeric anti-GD2 antibody (ch14.18) + GM-CSF/IL2 immunotherapy in 1st response: a children's oncology group study. ANR 2014;2014:abstract-PL013
100. Ladenstein RL, Poetschger U, Luksch R, et al. Immunotherapy (IT) with ch14.18/CHO for high-risk neuroblastoma: First results from the randomised HR-NBL1/SIOPEN trial. J Clin Oncol 2014;32(Suppl):abstract 10026
101. Lode HN, Jensen C, Endres S, et al. Immune activation and clinical responses following long-term infusion of anti-GD 2 antibody ch14. 18/CHO in combination with interleukin-2 in high-risk neuroblastoma patients. J Clin Oncol 2014;32(Supppl):abstract 10028
102. Millot F, Baruchel A, Guilhot J, et al. Imatinib is effective in children with previously untreated chronic myelogenous leukemia in early chronic phase: results of the French national phase IV trial. J Clin Oncol 2011;29:2827-32