Abstract
Chemotherapy for treatment of osteosarcoma was demonstrated to be effective in eradicating primary tumor and pulmonary metastases in the mid-twentieth century. The first agents that held promise were doxorubicin and high-dose methotrexate with leucovorin (citrovorin factor) in the mid-1970s. Since then, other agents that can eliminate or cause regression of tumor have been discovered: cis-diamminedichloroplatinum II (cisplatin) and the oxazaphosphorines ifosfamide and cyclophosphamide. Additional agents await further study to define their potential. The effective agents have been utilized in various combination regimens and have escalated the survival rate from <10 to 75 %. They have also enabled pulmonary metastectomy in patients with persistent and/or recurrent pulmonary metastases and tumor ablation and limb salvage in 80 % of newly diagnosed patients. Unfortunately, however, despite these impressive advances no change in survival expectancy of patients with osteosarcoma during the past 40 years has occurred. There have been no new chemotherapeutic agents effective in addressing disease that is resistant to current agents; the few that have been introduced await further study to substantiate their efficacy. This also includes attempts at alternate administration of chemotherapy (intra-arterial and inhalation therapy.) In this chapter, we provide an account of the sequential introduction of the chemotherapeutic agents, review the results of their application in selected regimens, and discuss the role of neoadjuvant chemotherapy.
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References
Gross SW (1879) Sarcomas of the long bones: based on a study of one hundred and sixty five cases. Am J Med Sci 8:338–377
Jaffe N, Frei E III, Traggis D et al (1974) Adjuvant methotrexate and citrovorin factor in osteogenic sarcoma. N Engl J Med 291:994–997
Jeffree GM, Price CH, Sissons HA (1975) The metastatic patterns of osteosarcoma. Br M Cancer 32(1):87–107
Friedman M, Carter SK (1972) The therapy of osteogenic sarcoma: current status and thoughts for the future. J Surg Oncol 4(5):482–510
Sullivan MP, Sutow WW, Taylor G (1963) L-phenylalanine mustard as treatment for metastatic osteogenic sarcoma in children. J Ped 63:227–237
Sutow WW, Sullivan MP, Fernbach DJ et al (1975) Adjuvant chemotherapy in primary treatment of osteogenic sarcoma. Cancer 36:1598–1602
Evans AE (1961) Mitomycin C. Cancer Chemother Rep 14:1–9
Frank W, Osterberg A (1971) Mitomycin C” (NSC-26980) clinical brochure. Cancer Chemother Rep 55:285–291
Finkelstein JZ, Hittle RE, Hammond CD (1969) Evaluation of a high dose cyclophosphamide regimen in childhood tumors. Cancer 23:1239–1242
Haggard M (1967) Cyclophosphamide (NSC-26271) in the treatment of children with malignant neoplasms. Cancer Chemother Rep 51:403–405
Pinkle D (1962) Cyclophosphamide in children with cancer. Cancer 15:42–49
Sutow WW, Vietti TJ, Fernbach DJ et al (1971) Evaluation of chemotherapy in children with metastatic Ewing’s sarcoma and osteogenic sarcoma. Cancer Chemother Rep 55:67–81
Selawry O, Holland J, Wolman J (1988) Effect of vincristine (NSC-67574) on malignant solid tumors in children. Cancer Chemother Rep 52:497–560
Groesbeck H, Budmore J (1963) Evaluation of 5-fluouracil (5-FU) in surgical practice. Am Surg 29:683–691
Jaffe N, Traggis D, Enriquez C (1971) Evaluation of mitomycin C (NSC-26980), phenylalanine mustard (NSC-16210) and vincristine (NSC-67574) in the treatment of osteogenic sarcoma. Cancer Chemother Rep 55:181–191
Sutow WW (1975) Combination chemotherapy with Adriamycin (NSC-123127) in primary treatment of osteosarcoma (Part III). Cancer Chemother Rep 6:315–317
Sutow WW, Gehan EA, Dyment PC et al (1978) Multi-drug adjuvant chemotherapy in osteosarcoma: interim report of the Southwest Oncology Group Studies. Cancer Treat Rep 62(2):265–269
Wilbur J (1974) Combination chemotherapy for rhabdomyosarcoma. Cancer Chemother Rep 58(2):281–284
Herson J, Sutow WW, Elder K (1980) Adjuvant chemotherapy in non-metastatic osteosarcoma: a Southwest Oncology Group Study. Med Pediatr Oncol 8:343–352
Cortez EP, Holland JF, Wang JJ et al (1972) Doxorubicin in disseminated osteosarcoma. JAMA 221:1132–1137
Bonnaonna G, Monifardi S, Douglass RC et al (1970) Phase I and preliminary phase II evaluation of Adriamycin (NSC-123127). Cancer Res 30:2572–2582
Cortez EP, Holland JF, Wang JJ et al (1972) Chemotherapy of adjuvant osteosarcoma. In: Proceedings of the 24th Symposium of the Colston Research Society, April, 1972. Butterworths, London
Gottlieb JA, Baker LH, O’Bryan RM et al (1975) Adriamycin (NSC-123127) used alone and in combination with soft tissue bone sarcoma. Cancer Chemother Rep 3:271–282
Middleman E, Luce L, Frei E (1971) Clinical trials with Adriamycin. Cancer 28:844–850
O’Bryan RM, Luce JK, Talley R et al (1973) Phase II evaluation of Adriamycin in human neoplasia. Cancer 32:1–7
Cortez EP, Holland JF, Wang JJ et al (1974) Amputation and Adriamycin in primary osteosarcoma. N Engl J Med 291:998–1000
Cassady JR, Richter MP, Piro AJ et al (1975) Radiation Adriamycin interactions-preliminary clinical observations. Cancer 36:946–949
Eilber FR, Grant T, Morton DC (1978) Adjuvant chemotherapy for osteosarcoma. Cancer Treat Rep 62:213–216
Seifert CF, Nesser ME, Thompson DF (1994) Dexrazoxane in the prevention of doxorubicin-induced cardiotoxicity. Ann Pharmacother 28:1063–1072
Smith MA, Ungerleider RS, Horowitz ME et al (1991) Influence of doxorubicin dose intensity on response and outcome for patients with osteogenic sarcoma and Ewing’s sarcoma. J Nat Cancer Inst 83:1460–1470
Farber S, Diamond LK, Mercer RD et al (1946) Temporary remissions in children in acute leukemia produced by folic acid antagonist 4-aminopteroyl-glutamic acid (aminopterin). N Engl J Med 238:787–793
Fyfe MJ, Goldman ID (1973) Characteristics of the vincristine augmentation of methotrexate uptake in Ehrlich ascites tumor cells. J Biol Chem 248:5067–5073
Goldin A, Mantel N, Greenhouse SW et al (1954) Effect of delayed administration of citrovorum factor on the antileukemic effectiveness of aminopterin in mice. Cancer Res 14:43–48
Djerassi I, Abir E, Boyer GL et al (1966) Long-term remissions in childhood acute leukemia: use of infrequent infusions of methotrexate; supportive roles of platelet transfusions and citrovorum factor. Clin Pediatr 5:502–509
Jaffe N (1972) Recent advances in the chemotherapy of osteogenic sarcoma. Cancer 30:1627–1631
Skipper HE, Schabel FM, Wilcox WS (1964) Experimental evaluation of potential anticancer agents. XIV Further study of certain basic concepts underlying chemotherapy of leukemia. Cancer Chemother Rep 35:1–28
Laster WR Jr, Mayo JG, Simpson-Herrin L et al (1969) Success and failure in the treatment of solid tumors. II. Kinetic parameters and “cell cure” of moderately advanced carcinoma. Cancer Chemother Rep 53:169–188
Schabel FM Jr (1975) Concepts for systemic treatment of micro-metastases. Cancer 35:15–24
Jaffe N (1974) Progress report on high-dose methotrexate (NSC-740) with citrovorum rescue in the treatment of metastatic bone tumor. Cancer Chemother Rep 58:275–280
Jaffe N, Traggis D (1975) Toxicity of high-dose methotrexate (NSC-740) and citrovorum factor (NSC-3590) in osteogenic sarcoma. Cancer Chemother Rep 6:31–36
Jaffe N, Traggis D, Cassady JR et al (1976) Multidisciplinary treatment for macrometastatic osteogenic sarcoma. Br Med J 2:1039–1041
Frei E III, Jaffe N, Tattersall MHN, Pitman S, Parker L (1975) New approaches to cancer chemotherapy with methotrexate. N Engl J Med 292:846–851
Pratt C, Shanks E, Hustu O et al (1977) Adjuvant multiple drug chemotherapy for osteosarcoma of the extremity. Cancer 39:51–57
Rosen G, Tefft M, Martinez A et al (1975) Combination chemotherapy and radiation therapy in the treatment of metastatic osteosarcoma. Cancer 35:622–630
Muggia FM, Louis AC (1978) Five years of adjuvant chemotherapy: more questions than answers. Cancer Treat Rep 62:30–36
Taylor WF, Ivins JC, Prichard DJ et al (1985) Trends and variability in survival among patients with osteosarcoma: a 7-year update. Mayo Clin Proc 60(2):91–104
Edmonson JH, Green SJ, Ivins JC et al (1984) A controlled pilot study of high-dose methotrexate as postsurgical adjuvant treatment for primary osteosarcoma. J Clin Oncol 2:152–156
Carter SK (1984) Adjuvant chemotherapy in osteogenic sarcoma: the triumph that isn’t? J Clin Oncol 2:147–148
Gehan EA, Sutow WW, Urube Botero T et al (1978) Osteosarcoma. The MD Anderson Experience 1850-1974. In: Terry WD, Windhorst D (eds) Immunotherapy of cancer. Present status of trials in man. Raven, New York, NY, pp 271–282
Mike V, Marcove RC (1978) Osteogenic sarcoma under the age of 21. Experiences at Memorial Sloan Kettering Cancer Center. In: Terry WD, Windhorst D (eds) Immunotherapy of cancer. Present status of trials in man. Raven, New York, NY, pp 283–292
Frei E III, Blum R, Jaffe N (1978) Sarcoma: natural history and treatment. In: Terry WD, Windhorst D (eds) Immunotherapy of cancer. Present status of trials in man. Raven, New York, NY, pp 248–255
Campanacci M, Bacci G, Bertoni F et al (1981) The treatment of osteosarcoma of the extremities: twenty years’ experience at the Instituto Ortopedico Rizzoli. Cancer 48:1569–1581
Link MP, Vietti TJ (1983) Role of adjuvant chemotherapy in the treatment of osteosarcoma. Cancer Treat Rep 67:744–745
Lang EB, Levin AS (1982) Is it ethical not to conduct a prospectively controlled trial of adjuvant chemotherapy in osteosarcoma? Cancer Treat Rep 66:1699–1704
Link MP, Goorin AM, Miser A et al (1986) The effect of adjuvant chemotherapy on relapse-free survival in patients with osteosarcoma of the extremity. N Engl J Med 314:1600–1606
Eilber FR, Douglass HI Jr, Mendel ER et al (1986) Adjuvant Adriamycin and cisplatin in newly diagnosed nonmetastatic osteosarcoma of the extremity. J Clin Oncol 4:353–362
Jaffe N (1986) Osteosarcoma. N Engl J Med 314:1513
Holland JF (1987) Adjuvant chemotherapy of osteosarcoma: no runs, no hits, two men left on base. J Clin Oncol 5:4–6
Jaffe N, Gorlick R (2008) High-dose methotrexate in osteosarcoma: let the questions surcease—time for final acceptance. J Clin Oncol 24:4365–4366
Van Dalen EC, van As JW, de Camargo B Methotrexate for high-grade osteosarcoma in children and young adults. Cochrane Database of Systematic Reviews 2011, Issue 5. Art. No.: CD006325. doi: 10.1002/14651858.CD006325.pub3
Jaffe N, Robertson R, Ayala A, Wallace S (1985) Comparison of intra-arterial CDP II with high-dose methotrexate and citrovorum factor rescue in the treatment of primary osteosarcoma. J Clin Oncol 3:1101–1104
Jaffe N (1979) Antifolate rescue use of high-dose methotrexate and citrovorin factor. In: Rossowsky A (ed) Advances in chemotherapy. Marcel Decker Inc., New York, NY, pp 111–141
Rosenberg B, Van Camp L, Krigas T (1965) Inhibition of cell division in Escherichia coli by electrolysis products from a platinum electrode. Nature 205(4972):698–699
Baum E, Greenberg L, Gaynon P et al (1978) Use of cis–diamminedichloroplatinum–II (CDDP) in osteogenic sarcoma in children (Abstract C-315). Proc AACR-ASCO 19:385
Nitschke R, Starling KA, Vats T et al (1978) Cis-diamminedichloroplatinum II (NSC119875) In: Childhood malignancies. A Southwest Oncology Group study. Med Pediatr Oncol 4:127–132
Ochs JJ, Freeman AI, Douglass HO Jr et al (1978) Cis-diamminedichloroplatinum (II) in advanced osteogenic sarcoma. Cancer Treat Rep 62:239–245
Pratt CB, Champion JE, Senzer N et al (1985) Treatment of unresectable or metastatic osteosarcoma with cisplatin or cisplatin–doxorubicin. Cancer 56:1930–1933
Jaffe N, Knapp J, Chuang VP et al (1983) Osteosarcoma intra-arterial treatment of the primary tumor with cis-diamminedichloroplatinum-II (CDP). Angiographic, pathologic and pharmacologic studies. Cancer 51:402–407
Jaffe N, Raymond AK, Ayala A et al (1989) Effect of cumulative courses of intra-arterial cis-diamminedichloroplatinum II on the primary tumor in osteosarcoma. Cancer 63:63–68
Jaffe N (2009) Osteosarcoma: review of the past, impact on the future. The American experience. In: Jaffe N, Bruland O, Bielack S (eds) Pediatric and adolescent osteosarcoma. Springer, New York, NY, pp 239–262
Hudson M, Jaffe MR, Jaffe N et al (1990) Pediatric osteosarcoma: therapeutic strategies, results and prognostic factors derived from a 10-year experience. J Clin Oncol 8:1988–1997
Lin PP, Patel S (2013) Osteosarcoma. In: Lin PP, Patel S (eds) Bone sarcoma. Springer, New York, NY, pp 75–97
Petrilli AS, de Camargo B, Filho VO et al (2006) Results of the Brazilian Osteosarcoma Treatment Group Studies III and IV: prognostic factors and impact on survival. J Clin Oncol 24:1161–1168
Goodman LS, Wintrobe MM, Dameshek W et al (1946) Nitrogen mustard therapy. JAMA 132(3):126–132
Sutow WW, Sullivan MP, Wilbur JR et al (1975) The study of adjuvant chemotherapy in osteogenic sarcoma. J Clin Pharmacol 15:530–533
Antman KH, Montella D, Rosenbaum C et al (1985) Phase II trial of ifosfamide with mesna in previously treated metastatic osteosarcoma. Cancer Treat Rep 69:499–504
Bowman LG, Mayer WN, Douglass EC et al (1987) Activation of ifosfamide in metastatic and unresectable osteosarcoma (Abstract). Proc ASCO C-214:844
Meyer WH, Pratt CB, Farham D et al (1988) The activity of ifosfamide (IFOS) in previously pretreated patients with osteosarcoma (OS): preliminary results of SJCRH OS-86 Study. Proc ASCO 7:26180
Goorin AM, Harris MB, Bernstein M et al (2002) Phase II/III trial of etoposide and high–dose ifosfamide in newly diagnosed metastatic osteosarcoma: a Pediatric Oncology Group Trial. J Clin Oncol 20:426–433
Kleinerman ES, Jia S-F, Griffin J (1992) Phase II study of liposomal muramyl tripeptide in osteosarcoma: the cytokine cascade and monocyte activation following administration. J Clin Onc 10(8):1310–1316
Meyers P, Schwartz CL, Krailo M et al (2008) Osteosarcoma: the addition of muramyl tripeptide to chemotherapy improves overall survival – a report from the Children’s Oncology Group. J Clin Oncol 26:633–688
Navid F, Willert JR, McCarville MB et al (2008) Combination of gemcitabine and docetaxel in the treatment of children and young adults with refractory bone sarcoma. Cancer 113:419–425
Fox E, Aplenc R, Bagatell R (2010) 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 28:5174–5181
Andrews NA (2013) Osteosarcoma therapy: what is the way forward? IBMS BoneKEy, doi 1038/bonekey.2013.106
Arndt CAS, Koshkina NV, Inwards CY (2010) Inhaled granulocyte macrophage colony stimulating factor for first pulmonary recurrence of osteosarcoma on disease-free survival and immunomodulation. A report from the Children’s Oncology Group. Cancer Clin Res 16:4024–4030
Chou AJ, Gupta R, Bell MD et al (2013) Inhaled lipid cisplatin (ILC) in the treatment of patients with relapsed progressive osteosarcoma metastatic to the lung. Ped Blood Can 60(4):580–586
Rosen G, Caparros B, Huvos AG et al (1982) Preoperative chemotherapy for osteogenic sarcoma: selection of postoperative adjuvant chemotherapy based on the response of the primary tumor to preoperative chemotherapy. Cancer 49:1221–1230
Huvos AG, Rosen G, Marcove RC (1997) Primary osteogenic sarcoma: pathologic aspects in 20 patients after treatment with chemotherapy, en bloc resection, and prosthetic bone replacement. Arch Pathol Lab Med 101:14–18
DeVita VT (1983) The relationship between tumor mass and resistance to chemotherapy. Implications for surgical adjuvant treatment of cancer. Cancer 51:1209–1220
Goldie JH, Coleman AJ (1979) A mathematical model for relating the drug sensitivity of tumors to their spontaneous mutation rate. Cancer Treat Rep 63:1727–1733
Murray JA, Jessup K, Romsdahl M et al (1985) Limb salvage surgery in osteosarcoma: early experience at MD Anderson Hospital and Tumor Institute. Cancer Treat Symp 3:131–137
Picci P, Bacci G, Campanna R et al (1988) Neoadjuvant chemotherapy for osteosarcoma - results of a prospective study. In: Ryan JR, Baker LO (eds) Recent concepts in sarcoma treatment. Kluver Academic Publishers, Dordrecht, pp 291–295
Picci P, Bacci G, Neff JR (1990) The influence of preoperative chemotherapy (POC) in the surgical planning in patients (PTS) with osteosarcoma (OS): a histopathological study on 205 PTS. Proc ASCO 9:310
Jaffe N, Spears R, Eftekhari F et al (1987) Pathologic fracture in osteosarcoma: effect of chemotherapy in primary tumor and survival. Cancer 59:701–709
Schabel FM Jr (1969) The use of tumor growth kinetics in planning “curative” chemotherapy of advanced solid tumors. Cancer Res 29:2384–2389
Schabel FM (1977) Rationale for adjuvant chemotherapy. Cancer 39:2875–2882
Nachman J, Simon MA, Dean L et al (1987) Disparate histologic prognosis in simultaneously resected primary and metastatic osteosarcoma following intravenous neoadjuvant chemotherapy. J Clin Oncol 5:1185–1190
Meyers PA, Heller G, Healy J et al (1992) Chemotherapy for non metastatic osteogenic sarcoma. The Memorial Sloan Kettering Experience. J Clin Oncol 10:5–13
Winkler K, Beron G, Dellin G et al (1988) Neoadjuvant chemotherapy for osteosarcoma: results of a randomized cooperative trial (COSS-82) with salvage chemotherapy based on histological tumor response. J Clin Oncol 6:329–337
Goorin AM, Schwartzentruber DJ, Devidas M et al (2003) Presurgical chemotherapy compared with immediate surgery and adjuvant chemotherapy for non metastatic osteosarcoma. Pediatric Oncology Group Study POG-8651. J Clin Oncol 21:1574–1580
Proviser AJ, Ettinger LJ, Nachman JB et al (1997) Treatment of non metastatic osteosarcoma of the extremity with preoperative and postoperative chemotherapy: a report from the Children’s Cancer Group. J Clin Oncol 15(1):1076–1084
Smeland B, Muller C, Alvegard TA et al (2003) Scandinavian Sarcoma Group Osteosarcoma Study SSG VIII: prognostic factors for outcome and the role of replacement salvage chemotherapy for poor histological responders. Eur J Cancer 30(4):488–494
Benjamin RS, Chawala SP, Murray J et al (1984) Preoperative chemotherapy for osteosarcoma: a treatment approach facilitating limb salvage with major prognostic indications. In: Jones SF, Salmon SE (eds) Adjuvant therapy of cancer IV. Grune and Stratton, Philadelphia, PA, pp 601–610
Marina N, Bielack S, Whelan S et al (2009) International collaboration is feasible in trials for rare conditions: the EURAMOS experience. In: Jaffe N, Bruland O, Bielack S (eds) Pediatric and adolescent osteosarcoma. Springer, New York, NY, pp 339–353
Bielack SS, Smeland S, Whelan J et al (2013) MAP plus maintenance pegylated interferon α-2b (MAPIfn) versus MAP alone in patients with resectable high-grade osteosarcoma and good histologic response to preoperative MAP: first results of the EURAMOS-“good response” randomization. J Clin Oncol 31 (suppl; abstr LBA10504)
Briccoli A, Rocca M, Salone M et al (2005) Resection of recurrent pulmonary metastases in patients with osteosarcoma. Cancer 104(8):1721–1725
Martini N, McCormack PM (1988) Pulmonary resection in sarcoma metastases. In: Ryan JR, Baker LO (eds) Recent concepts in sarcoma treatment. Kluwer Academic Publishers, Dordrecht, pp 197–200
Jaffe N, Smith E, Abelson HT et al (1983) Osteogenic sarcoma: alterations in the pattern of pulmonary metastases with adjuvant chemotherapy. J Clin Oncol 1:252–254
Harting MT, Blakely ML, Jaffe N et al (2006) Long-term survival after aggressive resection of pulmonary metastases among children and adolescents with osteosarcoma. J Pediatr Surg 41(1):194–199
Phemister DB (1940) Conservative surgery in the treatment of bone tumors. Surg Gynecol Obstet 70:355–364
Parrish FF (1968) Treatment of bone tumors by total excision and replacement with massive autologous and homologous grafts. J Bone Joint Surg 48A:968–990
Jaffe N, Carrasco H, Raymond K et al (2002) Can cure in patients with osteosarcoma be achieved exclusively with chemotherapy and abrogation of surgery? Cancer 95:2202–2210
McCarten KM, Jaffe N, Kirkpatrick JA (1980) The changing radiographic appearance of osteosarcoma. Ann Radiol 23:203–208
Bielack S, Jurgens H, Jundt G et al (2009) Osteosarcoma: the COSS experience. In: Jaffe N, Bruland O, Bielack S (eds) Pediatric and adolescent osteosarcoma. Springer, New York, NY, pp 289–308
Myers PA, Gorlick R, Heller G et al (1998) Intensification of preoperative chemotherapy for osteogenic sarcoma: results of the Memorial Sloan Kettering (T12) protocol. J Clin Oncol 16(7):2452–2458
Ferrari S, Palmerini E, Staals EL et al (2009) The treatment of nonmetastatic high-grade osteosarcoma of the extremity: review of the Italian Rizzoli experience. Impact on the future experience. In: Jaffe N, Bruland O, Bielack S (eds) Pediatric and adolescent osteosarcoma. Springer, New York, NY, pp 275–287
Bruland OS, Bauer H, Alvegard T et al (2009) Treatment of osteosarcoma. The Scandinavia Sarcoma Group experience. In: Jaffe N, Bruland O, Bielack S (eds) Pediatric and adolescent osteosarcoma. Springer, New York, NY, pp 309–318
Delepine N, Delepine G, Jasmine C et al (1988) Importance of age and methotrexate dosage: prognosis in children and young adults with high-grade osteosarcoma. Biomed Pharmacother 42:257–262
Le Deley M-C, Guinebretiere J-M, Gentet J-C (2007) A randomized trial comparing preoperative high-methotrexate plus doxorubicin to high dose methotrexate plus etoposide and ifosfamide in osteosarcoma patients. Eur J Cancer 43(4):751–761
Pratt CB, Luo X, Fay L et al (1996) Response of pediatric malignant solid tumors following ifosfamide or ifosfamide/carboplatin/etoposide. A single hospital experience. Med Pediatr Oncol 27:145–148
Daw NE, Neel MD, Rao BN (2011) Frontline treatment of localized osteosarcoma without methotrexate: results of the St Jude Children’s Research Hospital OS99 trial. Cancer 117(12):2770–2778
Meyer WH, Pratt CB, Poquette CA et al (2001) Carboplatin/ifosfamide window therapy for osteosarcoma: results of the St Jude Children’s Research Hospital OS-91 trial. J Clin Oncol 19:171–182
Krailo M, Ertel I, Makley J et al (1987) A randomized study comparing high dose methotrexate with moderate dose methotrexate as components of adjuvant therapy in childhood nonmetastatic osteosarcoma: a report from the Children’s Cancer Study Group. Med Pediatr Oncol 15:69–77
Ayan I, Kebudi R, Ozger H (2009) Childhood osteosarcoma: multimodal therapy in a single-institution Turkish series. In: Jaffe N, Bruland O, Bielack S (eds) Pediatric and adolescent osteosarcoma. Springer, New York, NY, pp 319–338
Bernthal N, Federman N, Nelson S (2012) Early pathologic response to neoadjuvant therapy predictive of long term (>25 year) survival in osteosarcoma. Paper presented at 2012 annual meeting of the Connective Tissue Oncology Society, Prague, Czech Republic, and 14–17 November 2012
Craft AW (2009) Osteosarcoma: the European Osteosarcoma Intergroup (EOI) perspective. In: Jaffe N, Rutland O, Bielack S (eds) Pediatric and adolescent osteosarcoma. Springer, New York, NY, pp 263–274
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Jaffe, N. (2014). Historical Perspective on the Introduction and Use of Chemotherapy for the Treatment of Osteosarcoma. In: Kleinerman, M.D., E. (eds) Current Advances in Osteosarcoma. Advances in Experimental Medicine and Biology, vol 804. Springer, Cham. https://doi.org/10.1007/978-3-319-04843-7_1
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