Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Pediatric Drugs
Published in: Pediatric Drugs 5/2008

01-09-2008 | Review Article

Therapy for Osteosarcoma

Where Do We Go From Here?

Authors: Alexander J. Chou, David S. Geller, Dr Richard Gorlick

Published in: Pediatric Drugs | Issue 5/2008

Login to get access

Abstract

Osteosarcoma is the most common malignant primary bone tumor in children and adolescents. Current optimal treatment for osteosarcoma consists of multi-agent chemotherapy and aggressive surgical resection of all sites of disease involvement. The current national and international cooperative trial for patients with newly diagnosed osteosarcoma builds upon the backbone of cisplatin, doxorubicin, and methotrexate. This protocol is designed to clarify whether (i) the addition of ifosfamide and etoposide to postoperative chemotherapy with cisplatin, doxorubicin, and methotrexate improves the event-free survival and overall survival for patients with resectable osteosarcoma and a poor histologic response to 10 weeks of preoperative chemotherapy; and (ii) the addition of pegylated interferon-α-2b as maintenance therapy after postoperative chemotherapy with cisplatin, doxorubicin, and methotrexate improves the event-free survival and overall survival for patients with resectable osteosarcoma and a good histologic response to 10 weeks of preoperative chemotherapy. However, the optimal treatment strategy (or strategies) for patients with relapsed or metastatic disease has yet to be defined. This remains one of the persistent challenges in the treatment of osteosarcoma.
Recent therapeutic advances have focused on circumventing chemotherapy resistance mechanisms, incorporation of non-classical agents into upfront therapy, targeting of the tumor micro-environment, and investigating the role of novel delivery mechanisms.
In patients with localized disease the 5-year survival rate is at least 70%; patients with metastatic or recurrent disease have <20% chance of long-term survival despite aggressive therapies. These figures have changed little in the past 2 decades. This review focuses on the current therapy for osteosarcoma, and highlights emerging strategies that will hopefully change the outlook for patients with this disease.
Footnotes
1
The use of trade names is for product identification purposes only and does not imply endorsement.
 
Literature
1.
2.
Arndt CA, Crist WM. Common musculoskeletal tumors of childhood and adolescence. N Engl J Med 1999 Jul 29; 341(5): 342–52PubMedCrossRef
3.
Chou AJ, Merola PR, Wexler LH, et al. Treatment of osteosarcoma at first recurrence after contemporary therapy: the Memorial Sloan-Kettering Cancer Center experience. Cancer 2005 Nov 15; 104(10): 2214–21PubMedCrossRef
4.
Ferrari S, Briccoli A, Mercuri M, et al. Postrelapse survival in osteosarcoma of the extremities: prognostic factors for long-term survival. J Clin Oncol 2003 Feb 15; 21(4): 710–5PubMedCrossRef
5.
Hawkins DS, Arndt CA. Pattern of disease recurrence and prognostic factors in patients with osteosarcoma treated with contemporary chemotherapy. Cancer 2003 Dec 1; 98(11): 2447–56PubMedCrossRef
6.
Marina N, Gebhardt M, Teot L, et al. Biology and therapeutic advances for pediatric osteosarcoma. Oncologist 2004; 9(4): 422–41PubMedCrossRef
7.
8.
9.
Hauben EI, Weeden S, Pringle J, et al. Does the histological subtype of high-grade central osteosarcoma influence the response to treatment with chemotherapy and does it affect overall survival? A study on 570 patients of two consecutive trials of the European Osteosarcoma Intergroup. Eur J Cancer 2002 Jun; 38(9): 1218–25PubMedCrossRef
10.
Nakajima H, Sim FH, Bond JR, et al. Small cell osteosarcoma of bone: review of 72 cases. Cancer 1997 Jun 1; 79(11): 2095–106PubMedCrossRef
11.
Bertoni F, Present D, Bacchini P, et al. The Istituto Rizzoli experience with small cell osteosarcoma. Cancer 1989 Dec 15; 64(12): 2591–9PubMedCrossRef
12.
Gibbs CP, Kukekov VG, Reith JD, et al. Stem-like cells in bone sarcomas: implications for tumorigenesis. Neoplasia 2005 Nov; 7(11): 967–76PubMedCrossRef
13.
Tolar J, Nauta AJ, Osborn MJ, et al. Sarcoma derived from cultured mesenchymal stem cells. Stem Cells 2007 Feb; 25(2): 371–9PubMedCrossRef
14.
Ifergan I, Meller I, Issakov J, et al. Reduced folate carrier protein expression in osteosarcoma: implications for the prediction of tumor chemosensitivity. Cancer 2003 Nov 1; 98(9): 1958–66PubMedCrossRef
15.
Zhou H, Randall RL, Brothman AR, et al. Her-2/neu expression in osteosarcoma increases risk of lung metastasis and can be associated with gene amplification. J Pediatr Hematol Oncol 2003 Jan; 25(1): 27–32PubMedCrossRef
16.
Sandberg AA, Bridge JA. Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors: osteosarcoma and related tumors. Cancer Genet Cytogenet 2003 Aug; 145(1): 1–30PubMedCrossRef
17.
Bode AM, Dong Z. Post-translational modification of p53 in tumorigenesis. Nat Rev Cancer 2004 Oct; 4(10): 793–805PubMedCrossRef
18.
Classon M, Harlow E. The retinoblastoma tumour suppressor in development and cancer. Nat Rev Cancer 2002 Dec; 2(12): 910–7PubMedCrossRef
19.
Benassi MS, Molendini L, Gamberi G, et al. Alteration of pRb/p16/cdk4 regulation in human osteosarcoma. Int J Cancer 1999 Oct 22; 84(5): 489–93PubMedCrossRef
20.
David JP, Mehic D, Bakiri L, et al. Essential role of RSK2 in c-Fos-dependent osteosarcoma development. J Clin Invest 2005 Mar; 115(3): 664–72PubMed
21.
Nielsen GP, Burns KL, Rosenberg AE, et al. CDKN2A gene deletions and loss of p16 expression occur in osteosarcomas that lack RB alterations. Am J Pathol 1998 Jul; 153(1): 159–63PubMedCrossRef
22.
Wei G, Lonardo F, Ueda T, et al. CDK4 gene amplification in osteosarcoma: reciprocal relationship with INK4A gene alterations and mapping of 12q13 amplicons. Int J Cancer 1999 Jan 18; 80(2): 199–204PubMedCrossRef
23.
O’Keefe RJ, Guise TA. Molecular mechanisms of bone metastasis and therapeutic implications. Clin Orthop Relat Res 2003 Oct; 415 Suppl.: S100–4PubMedCrossRef
24.
Yang R, Hoang BH, Kubo T, et al. Over-expression of parathyroid hormone Type 1 receptor confers an aggressive phenotype in osteosarcoma. Int J Cancer 2007 Sep; 121(5): 943–54PubMedCrossRef
25.
Link MP, Gebhardt MC, Meyers PA. Osteosarcoma. 4th ed. Philadelphia (PA): Lippincott Williams and Wilkins, 2002
26.
Enneking WF. A system of staging musculoskeletal neoplasms. Clin Orthop Relat Res 1986 Mar; 204: 9–24PubMed
27.
28.
Enneking WF, Spanier SS, Goodman MA. A system for the surgical staging of musculoskeletal sarcoma. Clin Orthop Relat Res 1980 Nov–Dec; 153: 106–20PubMed
29.
Davis AM, Bell RS, Goodwin PJ. Prognostic factors in osteosarcoma: a critical review. J Clin Oncol 1994 Feb; 12(2): 423–31PubMed
30.
Eilber FR, Rosen G. Adjuvant chemotherapy for osteosarcoma. Semin Oncol 1989 Aug; 16(4): 312–22PubMed
31.
Gorlick R, Meyers PA. Osteosarcoma necrosis following chemotherapy: innate biology versus treatment-specific. J Pediatr Hematol Oncol 2003 Nov; 25(11): 840–1PubMedCrossRef
32.
van der Woude HJ, Bloem JL, Hogendoorn PC. Preoperative evaluation and monitoring chemotherapy in patients with high-grade osteogenic and Ewing’s sarcoma: review of current imaging modalities. Skeletal Radiol 1998 Feb; 27(2): 57–71PubMedCrossRef
33.
Brenner W, Bohuslavizki KH, Eary JF. PET imaging of osteosarcoma. J Nucl Med 2003 Jun; 44(6): 930–42PubMed
34.
Hawkins DS, Rajendran JG, Conrad 3rd EU, et al. Evaluation of chemotherapy response in pediatric bone sarcomas by [F-18]-fluorodeoxy-D-glucose positron emission tomography. Cancer 2002 Jun 15; 94(12): 3277–84PubMedCrossRef
35.
Hawkins DS, Schuetze SM, Butrynski JE, et al. [18F]Fluorodeoxyglucose positron emission tomography predicts outcome for Ewing sarcoma family of tumors. J Clin Oncol 2005 Dec 1; 23(34): 8828–34PubMedCrossRef
36.
Rougraff BT, Simon MA, Kneisl JS, et al. Limb salvage compared with amputation for osteosarcoma of the distal end of the femur: a long-term oncological, functional, and quality-of-life study. J Bone Joint Surg Am 1994 May; 76(5): 649–56PubMed
37.
Mankin HJ, Lange TA, Spanier SS. The hazards of biopsy in patients with malignant primary bone and soft-tissue tumors. J Bone Joint Surg Am 1982 Oct; 64(8): 1121–7PubMed
38.
Mankin HJ, Mankin CJ, Simon MA. The hazards of the biopsy, revisited. Members of the Musculoskeletal Tumor Society. J Bone Joint Surg Am 1996 May; 78(5): 656–63PubMed
39.
Eckardt JJ, Kabo JM, Kelley CM, et al. Expandable endoprosthesis reconstruction in skeletally immature patients with tumors. Clin Orthop Relat Res 2000 Apr; 373: 51–61PubMedCrossRef
40.
Hanlon M, Krajbich JI. Rotationplasty in skeletally immature patients: long-term followup results. Clin Orthop Relat Res 1999 Jan; 358: 75–82PubMedCrossRef
41.
Winkelmann WW. Type-B-IIIa hip rotationplasty: an alternative operation for the treatment of malignant tumors of the femur in early childhood. J Bone Joint Surg Am 2000 Jun; 82(6): 814–28PubMed
42.
Merkel KD, Gebhardt M, Springfield DS. Rotationplasty as a reconstructive operation after tumor resection. Clin Orthop Relat Res 1991 Sep; 270: 231–6PubMed
43.
Winkelmann WW. Rotationplasty. Orthop Clin North Am 1996 Jul; 27(3): 503–23PubMed
44.
Ruggieri P, De Cristofaro R, Picci P, et al. Complications and surgical indications in 144 cases of nonmetastatic osteosarcoma of the extremities treated with neoadjuvant chemotherapy. Clin Orthop Relat Res 1993 Oct; 295: 226–38PubMed
45.
Kempf-Bielack B, Bielack SS, Jurgens H, et al. Osteosarcoma relapse after combined modality therapy: an analysis of unselected patients in the Cooperative Osteosarcoma Study Group (COSS). J Clin Oncol 2005 Jan 20; 23(3): 559–68PubMedCrossRef
46.
Kayton ML, Huvos AG, Casher J, et al. Computed tomographic scan of the chest underestimates the number of metastatic lesions in osteosarcoma. J Ped Surg 2006 Jan; 41(1): 200–6CrossRef
47.
Pratt CB, Meyer WH, Howlett N, et al. Phase II study of 5-fluorouracil/leucovorin for pediatric patients with malignant solid tumors. Cancer 1994 Nov 1; 74(9): 2593–8PubMedCrossRef
48.
Link MP, Eilber F. Osteosarcoma. In: Pizzo PA, Poplack DG, editors. Principles and practice of pediatric oncology. 1st ed. Philadelphia (PA): JB Lippincott, 1989: 689–711
49.
Chello PL, Sirotnak FM, Dorick DM, et al. Cancer schedule-dependent synergism of methotrexate and vincristine against murine L1210 leukemia. Treat Rep 1979; 63(11–12): 1889–94
50.
Jaffe N, Robertson R, Ayala A, et al. Comparison of intra-arterial cis-diamminedichloroplatinum II with high-dose methotrexate and citrovorum factor rescue in the treatment of primary osteosarcoma. J Clin Oncol 1985; 3(8): 1101–4PubMed
51.
Bacci G, Avella M, Capanna R, et al. Neoadjuvant chemotherapy in the treatment of osteosarcoma of the extremities: preliminary results in 131 cases treated preoperatively with methotrexate and cisdiamminoplatinum. Ital J Orthop Traumatol 1988; 14(1): 23–39PubMed
52.
Grem JL, King SA, Wittes RE, et al. The role of methotrexate in osteosarcoma. J Natl Cancer Inst 1988 Jul 6; 80(9): 626–55PubMedCrossRef
53.
Link MP, Goorin AM, Miser AW, et al. The effect of adjuvant chemotherapy on relapse-free survival in patients with osteosarcoma of the extremity. N Engl J Med 1986 Jun 19; 314(25): 1600–6PubMedCrossRef
54.
Plowman PN. Bulk disease as the major problem in the cure of paediatric sarcomas. Prog Pediatr Surg 1989; 22: 45–63PubMedCrossRef
55.
Rosen G, Caparros B, Huvos AG, et al. Preoperative chemotherapy for osteogenic sarcoma: selection of postoperative adjuvant chemotherapy based on the response of the primary tumor to preoperative chemotherapy. Cancer 1982 Mar 15; 49(6): 1221–30PubMedCrossRef
56.
Rosen G, Marcove RC, Caparros B, et al. Primary osteogenic sarcoma: the rationale for preoperative chemotherapy and delayed surgery. Cancer 1979 Jun; 43(6): 2163–77PubMedCrossRef
57.
Carli M, Passone E, Perilongo G, et al. Ifosfamide in pediatric solid tumors. Oncology 2003; 65Suppl. 2: 99–104PubMedCrossRef
58.
Meyers PA, Schwartz CL, Krailo M, et al. Osteosarcoma: a randomized, prospective trial of the addition of ifosfamide and/or muramyl tripeptide to cisplatin, doxorubicin, and high-dose methotrexate. J Clin Oncol 2005; 23(9): 2004–11PubMedCrossRef
59.
Bacci G, Ferrari S, Bertoni F, et al. Long-term outcome for patients with nonmetastatic osteosarcoma of the extremity treated at the istituto ortopedico rizzoli according to the istituto ortopedico rizzoli/osteosarcoma-2 protocol: an updated report. J Clin Oncol 2000 Dec 15; 18(24): 4016–27PubMed
60.
Fuchs N, Bielack SS, Epler D, et al. Long-term results of the co-operative German-Austrian-Swiss osteosarcoma study group’s protocol COSS-86 of intensive multidrug chemotherapy and surgery for osteosarcoma of the limbs. Ann Oncol 1998 Aug; 9(8): 893–9PubMedCrossRef
61.
Schwartz C, Wexler L, Devidas M, et al. Non-metastatic osteosarcoma: response based augmentation of therapy [abstract no. 666]. Proceedings of the Connective Tissue Oncology Society 12th Annual Meeting; 2006 Nov 2–4; Venice, 11
62.
63.
Hristov B, Shokek O, Frassica DA. The role of radiation treatment in the contemporary management of bone tumors. J Natl Compr Canc Netw 2007 Apr; 5(4): 456–66PubMed
64.
DeLaney TF, Trofimov AV, Engelsman M, Suit HD. Advanced-technology radiation therapy in the management of bone and soft tissue sarcomas. Cancer Control 2005 Jan–Feb; 12(1): 27–35PubMed
65.
Merimsky O, Kollender Y, Inbar M, et al. Palliative treatment for advanced or metastatic osteosarcoma. Isr Med Assoc J 2004 Jan; 6(1): 34–8PubMed
66.
Nagarajan R, Clohisy D, Weigel B. New paradigms for therapy for osteosarcoma. Curr Oncol Rep 2005 Nov; 7(6): 410–4PubMedCrossRef
67.
Ozaki T, Flege S, Kevric M, et al. Osteosarcoma of the pelvis: experience of the Cooperative Osteosarcoma Study Group. J Clin Oncol 2003 Jan 15; 21(2): 334–41PubMedCrossRef
68.
DeLaney TF, Park L, Goldberg SI, et al. Radiotherapy for local control of osteosarcoma. Int J Radiat Oncol Biol Phys 2005 Feb 1; 61(2): 492–8PubMedCrossRef
69.
Anderson PM, Wiseman GA, Dispenzieri A, et al. High-dose samarium-153 ethylene diamine tetramethylene phosphonate: low toxicity of skeletal irradiation in patients with osteosarcoma and bone metastases. J Clin Oncol 2002 Jan 1; 20(1): 189–96PubMedCrossRef
70.
Saeter G, Hoie J, Stenwig AE, et al. Systemic relapse of patients with osteogenic sarcoma: prognostic factors for long term survival. Cancer 1995 Mar 1; 75(5): 1084–93PubMedCrossRef
71.
Kruh GD, Zeng H, Rea PA, et al. MRP subfamily transporters and resistance to anticancer agents. J Bioenerg Biomembr 2001 Dec; 33(6): 493–501PubMedCrossRef
72.
Nathan SS, Gorlick R, Bukata S, et al. Treatment algorithm for locally recurrent osteosarcoma based on local disease-free interval and the presence of lung metastasis. Cancer 2006 Oct 1; 107(7): 1607–16PubMedCrossRef
73.
Rodriguez-Galindo C, Shah N, McCarville MB, et al. Outcome after local recurrence of osteosarcoma: the St Jude Children’s Research Hospital experience (1970-2000). Cancer 2004 May 1; 100(9): 1928–35PubMedCrossRef
74.
Bacci G, Ferrari S, Mercuri M, et al. Predictive factors for local recurrence in osteosarcoma: 540 patients with extremity tumors followed for minimum 2.5 years after neoadjuvant chemotherapy. Acta Orthop Scand 1998 Jun; 69(3): 230–6PubMedCrossRef
75.
Brosjo O. Surgical procedure and local recurrence in 223 patients treated 1982–1997 according to two osteosarcoma chemotherapy protocols: the Scandinavian Sarcoma Group experience. Acta Orthop Scand 1999 Jun; 285 Suppl.: 58–61
76.
Weeden S, Grimer RJ, Cannon SR, et al. The effect of local recurrence on survival in resected osteosarcoma. Eur J Cancer 2001 Jan; 37(1): 39–46PubMedCrossRef
77.
Bagatell R, Gore L, Egorin MJ, et al. Phase I pharmacokinetic and pharmacodynamic study of 17-N-allylamino-17-demethoxygeldanamycin in pediatric patients with recurrent or refractory solid tumors: a pediatric oncology experimental therapeutics investigators consortium study. Clin Cancer Res 2007 Mar 15; 13(6): 1783–8PubMedCrossRef
78.
Khanna C, Prehn J, Hayden D, et al. A randomized controlled trial of octreotide pamoate long-acting release and carboplatin versus carboplatin alone in dogs with naturally occurring osteosarcoma: evaluation of insulin-like growth factor suppression and chemotherapy. Clin Cancer Res 2002 Jul; 8(7): 2406–12PubMed
79.
Mansky PJ, Liewehr DJ, Steinberg SM, Chrousos GP, Avila NA, Long L, et al. Treatment of metastatic osteosarcoma with the somatostatin analog OncoLar: significant reduction of insulin-like growth factor-1 serum levels. J Pediatr Hematol Oncol 2002 Aug–Sep; 24(6): 440–6PubMedCrossRef
80.
Laverdiere C, Kolb EA, Supko JG, et al. Phase II study of ecteinascidin 743 in heavily pretreated patients with recurrent osteosarcoma. Cancer 2003 Aug 15; 98(4): 832–40PubMedCrossRef
81.
Kleinerman ES. Biologic therapy for osteosarcoma using liposome-encapsulated muramyl tripeptide. Hematol Oncol Clin North Am 1995 Aug; 9(4): 927–38PubMed
82.
Chou AJ, Gorlick R. Chemotherapy resistance in osteosarcoma: current challenges and future directions. Expert Rev Anticancer Ther 2006 Jul; 6(7): 1075–85PubMedCrossRef
83.
Yang R, Kolb EA, Qin J, et al. The folate receptor alpha is frequently overexpressed in osteosarcoma samples and plays a role in the uptake of the physiologic substrate 5-methyltetrahydrofolate. Clin Cancer Res 2007 May 1; 13(9): 2557–67PubMedCrossRef
84.
Banerjee D, Ercikan-Abali E, Waltham M, et al. Molecular mechanisms of resistance to antifolates: a review. Acta Biochim Pol 1995; 42(4): 457–64PubMed
85.
Guo W, Healey JH, Meyers PA, et al. Mechanisms of methotrexate resistance in osteosarcoma. Clin Cancer Res 1999 Mar; 5(3): 621–7PubMed
86.
Yang R, Sowers R, Mazza B, et al. Sequence alterations in the reduced folate carrier are observed in osteosarcoma tumor samples. Clin Cancer Res 2003 Feb; 9(2): 837–44PubMed
87.
McGuire JJ. Anticancer antifolates: current status and future directions. Curr Pharm Des 2003; 9(31): 2593–613PubMedCrossRef
88.
89.
Tkaczewski I, Tong WP, Spriggs D, et al. Trimetrexate (TMTX) oral bioavailability and lack of cross resistance with HDMTX in patients with recurrent osteosarcoma (OS) [abstract 1504]. Proceedings of the American Society of Clinical Oncology Annual Meeting; 1996 May 18–21; Philadelphia (PA)
90.
Trippett T, Meyers P, Gorlick R, et al. High dose trimetrexate with leucovorin protection in recurrent childhood malignancies: a Phase II trial [abstract 889]. Proceedings of the American Society of Clinical Oncology Annual Meeting; 1999 May 15–19; Atlanta (GA)
91.
Chattopadhyay S, Moran RG, Goldman ID. Pemetrexed: biochemical and cellular pharmacology, mechanisms, and clinical applications. Mol Cancer Ther 2007 Feb; 6(2): 404–17PubMedCrossRef
92.
Rollins KD, Lindley C. Pemetrexed: a multitargeted antifolate. Clin Ther 2005 Sep; 27(9): 1343–82PubMedCrossRef
93.
Solomon B, Bunn Jr PA. Clinical activity of pemetrexed: a multitargeted antifolate anticancer agent. Future Oncol 2005 Dec; 1(6): 733–46PubMedCrossRef
94.
Villela LR, Stanford BL, Shah SR. Pemetrexed, a novel antifolate therapeutic alternative for cancer chemotherapy. Pharmacotherapy 2006 May; 26(5): 641–54PubMedCrossRef
95.
Walling J. From methotrexate to pemetrexed and beyond: a review of the pharmacodynamic and clinical properties of antifolates. Invest New Drugs 2006 Jan; 24(1): 37–77PubMedCrossRef
96.
Chidiac T, Budd GT, Pelley R, et al. Phase II trial of liposomal doxorubicin (Doxil) in advanced soft tissue sarcomas. Invest New Drugs 2000 Aug; 18(3): 253–9PubMedCrossRef
97.
Judson I, Radford JA, Harris M, et al. Randomised phase II trial of pegylated liposomal doxorubicin (DOXIL/CAELYX) versus doxorubicin in the treatment of advanced or metastatic soft tissue sarcoma: a study by the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer 2001 May; 37(7): 870–7PubMedCrossRef
98.
Muggia FM. Liposomal encapsulated anthracyclines: new therapeutic horizons. Curr Oncol Rep 2001 Mar; 3(2): 156–62PubMedCrossRef
99.
Skubitz KM. Phase II trial of pegylated-liposomal doxorubicin (Doxil) in sarcoma. Cancer Invest 2003 Apr; 21(2): 167–76PubMedCrossRef
100.
Alberts DS, Muggia FM, Carmichael J, et al. Efficacy and safety of liposomal anthracyclines in phase I/II clinical trials. Semin Oncol 2004 Dec; 31 (6 Suppl. 13): 53–90PubMedCrossRef
101.
Chou AJ, Bell MD, Mackinson C, et al. Phase Ib/IIa study of sustained release lipid inhalation targeting cisplatin by inhalation in the treatment of patients with relapsed/progressive osteosarcoma metastatic to the lung [abstract no. 9525]. Proceedings of the American Society of Clinical Oncology (ASCO) 43rd Annual Meeting; 2007 Jun 1–5; Chicago (IL). J Clin Oncol 2007; 25: 18S
102.
Rao RD, Markovic SN, Anderson PM. Aerosol therapy for malignancy involving the lungs. Curr Cancer Drug Targets 2003 Aug; 3(4): 239–50PubMedCrossRef
103.
Anderson PM, Markovic SN, Sloan JA, et al. Aerosol granulocyte macrophagecolony stimulating factor: a low toxicity, lung-specific biological therapy in patients with lung metastases. Clin Cancer Res 1999 Sep; 5(9): 2316–23PubMed
104.
Anderson PM, Pearson M. Novel therapeutic approaches in pediatric and young adult sarcomas. Curr Oncol Rep 2006 Jul; 8(4): 310–5PubMedCrossRef
105.
Khanna C, Anderson PM, Hasz DE, et al. Interleukin-2 liposome inhalation therapy is safe and effective for dogs with spontaneous pulmonary metastases. Cancer 1997 Apr 1; 79(7): 1409–21PubMedCrossRef
106.
Skubitz KM, Anderson PM. Inhalational interleukin-2 liposomes for pulmonary metastases: a phase I clinical trial. Anticancer Drugs 2000 Aug; 11(7): 555–63PubMedCrossRef
107.
Bjornsti MA, Houghton PJ. The TOR pathway: a target for cancer therapy. Nat Rev Cancer 2004 May; 4(5): 335–48PubMedCrossRef
108.
109.
Vilella-Bach M, Nuzzi P, Fang Y, et al. The FKBP12-rapamycin-binding domain is required for FKBP12-rapamycin-associated protein kinase activity and G1 progression. J Biol Chem 1999 Feb 12; 274(7): 4266–72PubMedCrossRef
110.
Wan X, Mendoza A, Khanna C, et al. Rapamycin inhibits ezrin-mediated metastatic behavior in a murine model of osteosarcoma. Cancer Res 2005 Mar 15; 65(6): 2406–11PubMedCrossRef
111.
Casas-Ganem J, Healey JH. Advances that are changing the diagnosis and treatment of malignant bone tumors. Curr Opin Rheumatol 2005 Jan; 17(1): 79–85PubMedCrossRef
112.
McGary EC, Weber K, Mills L, et al. Inhibition of platelet-derived growth factormediated proliferation of osteosarcoma cells by the novel tyrosine kinase inhibitor STI571. Clin Cancer Res 2002 Nov; 8(11): 3584–91PubMed
113.
Scotlandi K, Manara MC, Nicoletti G, et al. Antitumor activity of the insulin-like growth factor-I receptor kinase inhibitor NVP-AEW541 in musculoskeletal tumors. Cancer Res 2005 May 1; 65(9): 3868–76PubMedCrossRef
114.
Pollak MN, Polychronakos C, Richard M. Insulinlike growth factor I: a potent mitogen for human osteogenic sarcoma. J Natl Cancer Inst 1990 Feb 21; 82(4): 301–5PubMedCrossRef
115.
Burrow S, Andrulis IL, Pollak M, et al. Expression of insulin-like growth factor receptor, IGF-1, and IGF-2 in primary and metastatic osteosarcoma. J Surg Oncol 1998 Sep; 69(1): 21–7PubMedCrossRef
116.
Benini S, Baldini N, Manara MC, et al. Redundancy of autocrine loops in human osteosarcoma cells. Int J Cancer 1999 Feb 9; 80(4): 581–8PubMedCrossRef
117.
Chou A, Merola P, Sowers R, et al. Analysis of aberrant signal transduction pathways in osteosarcoma cell lines [abstract no. 4551]. Proceedings of the American Association of Cancer Research 96th Annual Meeting; 2005 Apr 16–20; Anaheim (CA), 46
118.
Akatsuka T, Wada T, Kokai Y,et al. ErbB2 expression is correlated with increased survival of patients with osteosarcoma. Cancer 2002 Mar 1; 94(5): 1397–404PubMedCrossRef
119.
Gorlick R, Huvos AG, Heller G, et al. Expression of HER2/erbB-2 correlates with survival in osteosarcoma. J Clin Oncol 1999 Sep; 17(9): 2781–8PubMed
120.
Hughes DP, Thomas DG, Giordano TJ, et al. Essential erbB family phosphorylation in osteosarcoma as a target for CI-1033 inhibition. Pediatr Blood Cancer 2006 May 1; 46(5): 614–23PubMedCrossRef
121.
Morris CD, Gorlick R, Huvos G, et al. Human epidermal growth factor receptor 2 as a prognostic indicator in osteogenic sarcoma. Clin Orthop Relat Res 2001 Jan (382): 59–65
122.
Scotlandi K, Manara MC, Hattinger CM, et al. Prognostic and therapeutic relevance of HER2 expression in osteosarcoma and Ewing’s sarcoma. Eur J Cancer 2005 Jun; 41(9): 1349–61PubMedCrossRef
123.
Somers GR, Ho M, Zielenska M, et al. HER2 amplification and overexpression is not present in pediatric osteosarcoma: a tissue microarray study. Pediatr Dev Pathol 2005 Sep–Oct; 8(5): 525–32PubMedCrossRef
124.
Charity RM, Foukas AF, Deshmukh NS, et al. Vascular endothelial growth factor expression in osteosarcoma. Clin Orthop Relat Res 2006 Jul; 448: 193–8PubMedCrossRef
125.
DuBois S, Demetri G. Markers of angiogenesis and clinical features in patients with sarcoma. Cancer 2007 Mar 1; 109(5): 813–9PubMedCrossRef
126.
Kaya M, Wada T, Akatsuka T, et al. Vascular endothelial growth factor expression in untreated osteosarcoma is predictive of pulmonary metastasis and poor prognosis. Clin Cancer Res 2000 Feb; 6(2): 572–7PubMed
127.
Kaya M, Wada T, Kawaguchi S, et al. Increased pre-therapeutic serum vascular endothelial growth factor in patients with early clinical relapse of osteosarcoma. Br J Cancer 2002 Mar 18; 86(6): 864–9PubMedCrossRef
128.
Lee YH, Tokunaga T, Oshika Y, et al. Cell-retained isoforms of vascular endothelial growth factor (VEGF) are correlated with poor prognosis in osteosarcoma. Eur J Cancer 1999 Jul; 35(7): 1089–93PubMedCrossRef
129.
Lee J, Hoang B, Chou A, et al. Expression of vascular endothelial growth factor correlates with chemotherapy response in osteosarcoma patients [abstract no. 3489]. Proceedings of the American Association for Cancer Research Annual Meeting 2007 Apr 14–18; Los Angeles (CA)
130.
Maris JM, Courtright J, Houghton PJ, et al. Initial testing of the VEGFR inhibitor AZD2171 by the pediatric preclinical testing program. Pediatr Blood Cancer 2008 Mar; 50(3): 581–7PubMedCrossRef
131.
Mintz MB, Sowers R, Brown KM, et al. An expression signature classifies chemotherapy-resistant pediatric osteosarcoma. Cancer Res 2005 Mar 1; 65(5): 1748–54PubMedCrossRef
132.
Guise TA, Yin JJ, Mohammad KS. Role of endothelin-1 in osteoblastic bone metastases. Cancer 2003 Feb 1; 97 (3 Suppl.): 779–84PubMedCrossRef
133.
Itoh Y, Tamai M, Yokogawa K, et al. Involvement of multidrug resistance-associated protein 2 in in vivo cisplatin resistance of rat hepatoma AH66 cells. Anticancer Res 2002 May–Jun; 22(3): 1649–53PubMed
134.
Wuyts W, Van Wesenbeeck L, Morales-Piga A, et al. Evaluation of the role of RANK and OPG genes in Paget’s disease of bone. Bone 2001 Jan; 28(1): 104–7PubMedCrossRef
135.
Miyamoto N, Higuchi Y, Mori K, et al. Human osteosarcoma-derived cell lines produce soluble factor(s) that induces differentiation of blood monocytes to osteoclast-like cells. Int Immunopharmacol 2002 Jan; 2(1): 25–38PubMedCrossRef
136.
Wittrant Y, Lamoureux F, Mori K, et al. RANKL directly induces bone morphogenetic protein-2 expression in RANK-expressing POS-1 osteosarcoma cells. Int J Oncol 2006 Jan; 28(1): 261–9PubMed
137.
Ashton JA, Farese JP, Milner RJ, et al. Investigation of the effect of pamidronate disodium on the in vitro viability of osteosarcoma cells from dogs. Am J Vet Res 2005 May; 66(5): 885–91PubMedCrossRef
138.
Cheng YY, Huang L, Lee KM, et al. Alendronate regulates cell invasion and MMP-2 secretion in human osteosarcoma cell lines. Pediatr Blood Cancer 2004 May; 42(5): 410–5PubMedCrossRef
139.
Ory B, Heymann MF, Kamijo A, et al. Zoledronic acid suppresses lung metastases and prolongs overall survival of osteosarcoma-bearing mice. Cancer 2005 Dec 1; 104(11): 2522–9PubMedCrossRef
140.
Houghton PJ, Morton CL, Kolb EA, et al. Initial testing (stage 1) of the proteasome inhibitor bortezomib by the pediatric preclinical testing program. Pediatr Blood Cancer 2008 Jan; 50(1): 37–45PubMedCrossRef
141.
Lock R, Carol H. Houghton PJ, et al. Initial testing (stage 1) of the BH3 memetic ABT-263 by the pediatric preclinical testing program. Pediatr Blood Cancer 2008 Jun; 50(6): 1181–0PubMedCrossRef
142.
Houghton PJ, Morton CL, Kolb EA, et al. Initial testing (stage 1) of the mTOR inhibitor rapamycin by the pediatric preclinical testing program. Pediatr Blood Cancer 2008 Apr; 50(4): 799–805PubMedCrossRef
143.
Maris JM, Courtright J, Houghton PJ, et al. Initial testing (stage 1) of sunitinib by the pediatric preclinical testing program. Pediatr Blood Cancer 2008 Jul; 51(1): 42–8PubMedCrossRef
Metadata
Title
Therapy for Osteosarcoma
Where Do We Go From Here?
Authors
Alexander J. Chou
David S. Geller
Dr Richard Gorlick
Publication date
01-09-2008
Publisher
Springer International Publishing
Published in
Pediatric Drugs / Issue 5/2008
Print ISSN: 1174-5878
Electronic ISSN: 1179-2019
DOI
https://doi.org/10.2165/00148581-200810050-00005

Other articles of this Issue 5/2008

Pediatric Drugs 5/2008 Go to the issue

Therapy In Practice

Treatment of Invasive Candidiasis in Immunocompromised Pediatric Patients

Commentary

The Need for and Creation of a Comprehensive Pediatric Research Network

Adis Drug Profile

Live Attenuated Measles, Mumps, Rubella, and Varicella Zoster Virus Vaccine (Priorix-Tetra™)

Original Research Article

Pharmacodynamic Target Attainment of Oral β-Lactams for the Empiric Treatment of Acute Otitis Media in Children

Therapy In Practice

Current Management of Tuberous Sclerosis Complex

Commentary

Improved Understanding of Genetic and Genomic Influences on Drug Disposition and Action