Aggiornamento monografico
Oncologia pediatrica: dalla diagnosi alla terapia, presente e futuro (parte seconda)
PAEDIATRIC ONCOLOGY: EVOLUTION OF DIAGNOSIS AND TREATMENT
PAOLO PAOLUCCI1, ILARIA MARIOTTI2, ELENA BIGI3, SIMONE SCHIAVO3, CARMEN CANO1
1UO di Ematologia e Oncologia Pediatrica;2Scuola di Specializzazione di Pediatria; 3Medico frequentatore; Università di Modena e Reggio Emilia
Marzo 2009 - pagg. 156 -161
Abstract
The objective of treatment for more than 70% of children with cancer outlines the successful routes built up by paediatric oncologists over the latest 40 years. In addition to the evolution of diagnostic routes reported in our former article, the second backbone of this successful story stands for the development of multicenter (national, international), cooperative, non-profit clinical trials. The therapeutic approach is based on limited surgery, radiotherapy and, principally, on chemotherapy protocols, part of controlled clinical studies as consequence of the progressive use of new drugs, new drug schedules and doses.
However, about 25% of children still die without additional efficacious therapeutic options and the treatment may often represent cause of early toxic events and even of long term sequelae. The progress of our understanding of the molecular bases of the neoplastic transformation has opened the possibility to interfere directly with genes and their altered products inside the tumour cell. Of course, the “dream“ to rely upon more specific substances selectively directed towards known “targets” evokes the advantages of a personalized and more specific medicine in favour of the reduction of early and long term toxicity, which does represent an important objective to pursue also with the presently available therapies.
Parole chiave
Classificazione MeSH
Bibliografia
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17. Klingebiel T, Boos J, Int-Veen C, et al. High dose chemotherapy versus oral maintenance: result of HD CW 96 study for treatment of patients with metastasized soft tissue sarcoma. Med Ped Oncol 2006;47:426.
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28. Testi AM, Biondi A, Lo Coco F, et al. GIMEMA- AIEOP AIDA protocol for the treatment of newly diagnosed acute promyelocytic leukemia (APL) in children. Blood 2005;106: 447-53.
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34. den Boer ML, Pieters R. Microarray-based identification of new targets for specific therapies in pediatric leukemia. Curr Drug Targets 2007;8:761-4.
35. Stubbs MC, Armstrong SA. FLT3 as a therapeutic target in childhood acute leukemia. Curr Drug Targets 2007;8:703-14.
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37. Regulation (EC) n. 1902/2006 of the European Parlament and of the Council of 20 December 2006 amending Regulation 1901/2006 on medicinal products for pediatric use. Official Journal of the European Union, 27.12. 2006, L378/20-L378/21.
2. Gaynon PS, Desai AA, Bostrom BC, et al. Early response to therapy and outcome in childhood acute lymphoblastic leukemia. Cancer 1997;80:1717-26.
3. Conter V, Aricò M, Valsecchi MG, et al. Long-term results of the Italian Association of Pediatric Hematology and Oncology (AIEOP) acute lymphoblastic leukemia studies, 1982-
1995. Leukemia 2000;14:2196-204.
4. Packer RJ, Gajjar A, Vezina G, et al. Phase III prospective randomized study of craniospinal radiation therapy followed by one of two adjuvant chemotherapy regimens for newly-diagnosed average risk medulloblastoma. J Clin Oncol 2006;24:4202-8.
5. Packer RJ, Sutton LN, Elterman R, et al. Outcome for children with medulloblastoma treated with radiation and cisplatin, CCNU and vincristine chemotherapy. J Neurosurg 1994;81:690-8.
6. Taylor RE, Bailey CC, Robinson K, et al. Results of a randomized study of pre-radiation chemotherapy vs radiotherapy regimen alone for non-metastatic (M0–M1) medulloblastoma. The SIOP/UKCCSG PNET-3 study. J Clin Oncol 2003;21:1581-91.
7. Taylor RE, Bailey CC, Robinson KJ et al. Outcome of patients with metastatic (M2–3) medulloblastoma treated with SIOP/ UKCCSG PNET-3 chemotherapy. Eur J Cancer 2005; 41:727-34.
8. Finaly JL, Goldman S, Wong MC, et al. Pilot study of high-dose thiotepa and etoposide with autologous bone marrow rescue in children and young adults with recurrent CNS tumors: the Children’s Cancer Study Group. J Clin Oncol 1996;14:2495-503.
9. Asgharzadeh S, Pique-Regi R, Sposto R, et al. Prognostic significance of gene expression profiles of metastatic neuroblastomas lacking MYCN gene amplification. J Natl Cancer Inst 2006;98:1193-203.
10. George RE, London WB, Cohn SL, et al. Hyperdiploidy plus nonamplified MYCN confers a favorable prognosis in children 12 to 18 months old with disseminated neuroblastoma: a Pediatric Oncology Group study. J Clin Oncol 2005;23:6466-73.
11. Rubie H, Chisholm J, Defachelles AS, et al. Phase II study of temozolomide in relapsed or refractory high-risk neuroblastoma: a joint Société Française des Cancers de l’Enfant and United Kingdom Children Cancer Study Group-New Agents Group Study. J Clin Oncol 2006;24:5259-64.
12. Viprey VF, Corrias MV, Kagedal B, et al. Standardisation of operating procedures for the detection of minimal disease by QRT-PCR in children with neuroblastoma: quality assurance on behalf of SIOPEN-R-NET. Eur J Cancer 2007;43:341-50.
13. Modak S, Cheung NK. Disialoganglioside directed immunotherapy of neuroblastoma. Cancer Invest 2007;25:66-77.
14. Ponthan F, Wickstrom M, Gleissman H, et al. Celecoxib prevents neuroblastoma tumor development and potentiates the effect of chemotherapeutic drugs in vitro and in vivo. Clin Cancer Res 2007;13:1036-44.
15. Breitfeld PP, Meyer WH. Rhabdomyosarcoma: new windows of opportunity. Oncologist 2005;10:518-27.
16. Pappo AS, Lyden E, Breitfeld P, et al. Children’s Oncology Group. Two consecutive phase II window trials of irinotecan alone or in combination with vincristine for the treatment of metastatic rhabdomyosarcoma: the Children’s Oncology Group. J Clin Oncol 2007;25: 362-9.
17. Klingebiel T, Boos J, Int-Veen C, et al. High dose chemotherapy versus oral maintenance: result of HD CW 96 study for treatment of patients with metastasized soft tissue sarcoma. Med Ped Oncol 2006;47:426.
18. Ferrari A, Casanova M, Collini P, et al. Adult-type soft tissue sarcomas in pediatricage patients: experience at the Istituto Nazionale Tumori in Milan. J Clin Oncol 2005;23: 4021-30.
19. Koscielniak E, Gross-Wieltsch U, Treuner J, et al. Graft-versus-Ewing sarcoma effect and long-term remission induced by haploidentical stem-cell transplantation in a patient with relapse of metastatic disease. J Clin Oncol 2005;23:242-4.
20. Ewing J. Further report on endothelial endothelioma of bone. Proc NY Pathol Soc 1924; 24:93-101.
21. Phillips RF, Higinbotham NL. The curability of Ewing’s endothelioma of bone in children. J Pediatr 1967;70:391-7.
22. Bacci G, Forni C, Longhi A, et al. Longterm outcome for patients with non-metastatic Ewing’s sarcoma treated with adjuvant and neoadjuvant chemotherapies. 402 patients treated at Rizzoli between 1972 and 1992. Eur J Cancer 2004;40:73-83.
23. Yukihide I. Diagnosis and treatment of Ewing’s Sarcoma. Jpn J Clin Oncol 2007;37:79- 89.
24. Look AT. Oncogenic transcription factors in the human acute leukemias. Science 1997; 278:1059-64.
25. Gilliland DG, Jordan CT, Felix CA. The molecular basis of leukemia. Haematology Am Soc Haematol Educ Program 2004;3:80-97.
26. Rambaldi A, Biondi A. Acute Promyelocytic Leukemia. In: Henderson ES, Lister TA, Greaves MF (Eds). Leukemia. 7th edition. Saunders, 2002:529-43.
27. Lo Coco F, Diverio D, Falini B, et al. Genetic diagnosis and molecular monitoring in the management of acute promyelocytic leukemia. Blood 1999;94:12-22.
28. Testi AM, Biondi A, Lo Coco F, et al. GIMEMA- AIEOP AIDA protocol for the treatment of newly diagnosed acute promyelocytic leukemia (APL) in children. Blood 2005;106: 447-53.
29. Savage DG, Antman KH. Imatinib mesylate- a new oral targeted therapy. N Engl J Med 2002;346:683-93.
30. Druker BJ. Imatinib as a paradigm of targeted therapies. Adv Cancer Res 2004;91:1-30.
31. Salomon DS, Brandt R, Ciardiello F, et al. Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol1995;19:183-232.
32. Downward J. Targeting RAS signalling pathways in cancer therapy. Nat Rev Cancer 2003;3:11-22.
33. Bjornsti MA, Houghton PJ. The TOR pathway: a target for cancer therapy. Nat Rev Cancer 2004;4:335-48.
34. den Boer ML, Pieters R. Microarray-based identification of new targets for specific therapies in pediatric leukemia. Curr Drug Targets 2007;8:761-4.
35. Stubbs MC, Armstrong SA. FLT3 as a therapeutic target in childhood acute leukemia. Curr Drug Targets 2007;8:703-14.
36. Armstrong SA, Kung AL, Mabon ME, et al. Inhibition of FLT3 in MLL. Validation of a therapeutic target identified by gene expression based classification. Cancer Cell 2003;3: 173-83.
37. Regulation (EC) n. 1902/2006 of the European Parlament and of the Council of 20 December 2006 amending Regulation 1901/2006 on medicinal products for pediatric use. Official Journal of the European Union, 27.12. 2006, L378/20-L378/21.
Corrispondenza: paolo.paolucci@unimore.it