High-dose Versus Moderate-dose Chemotherapy for Osteosarcoma: A Systematic Review_Chinese Journal of Evidence-Based Medicine

Authors：

LI Tongxiang ¹ , BAI Jingping ¹ , XILIN Boleri ¹ , JIANG Renbing ¹ , HE Zusheng ¹ , HUANG Weimin ² ,  WU Taixiang ³

1. The Affiliated Oncology Hospital of Xinjiang Medical University, Urumqi 830054, China 2. Xinjiang Jiangong Hospital, Urumqi 830002, China 3. Chinese Evidence-Based Medicine Centre/INCLEN CERTC, West China Hospital, Sichuan University, Chengdu 610041,China;

Corresponding author：

WU Taixiang, Email: 1971@163.com

Keywords：

Osteosarcoma; Chemotherapy; High-dose chemotherapy; Moderate-dose chemotherapy; Systematic review

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Objective 　To assess the efficacy of high-dose chemotherapy versus moderate-dose chemotherapy in the treatment of osteosarcoma.
Methods 　We searched MEDLINE, EMbase, OVID database, CBMdisc, Cochrane CENTRAL Register of Controlled Trials in The Cochrane Library, and handsearched Journal of Chinese Oncology, Journal of Chinese Clinical Oncology and Tumor. The search time was updated to Feburary 2006.The quality of the included studies was evaluated by two reviewers and meta-analyses were performed on the results of homogenous studies.
Results 　Four studies involving 937 participants with primary, high-grade and non-metastatic extremity osteosarcoma were included. All the included studies were judged to be inadequate at reporting randomization and blinding, only one reported allocation concealment. All included studies reported the number of withdrawals and the reasons for these. The meta-analyses showed that there were no significant differences in 5-year event free survival (EFS) (RR 1.10, 95% CI 0.96 to1.25), 5-year overall survival (OS) (RR 1.08, 95% CI 0.97 to1.20), local recurrence rate (RR 0.92, 95% CI 0.54 to 1.57), proportion of good histological response (RR 0.93, 95% CI 0.81 to 1.07), proportion of limb salvage [RR 0.97, 95% CI 0.92 to 1.02) between the high-dose group and the moderate-dose group. The 5-year EFS of the good histological response group was significantly higher than in the poor histological response group [OR 2.45, 95% CI 1.76 to 3.39,P lt;0.00001 ).
Conclusions 　No advantage is shown for high-dose chemotherapy over moderate-dose chemotherapy in 5-year EFS, 5-year OS, local recurrence rate, proportion of good histological response and proportion of limb salvage. Histological response to preoperative chemotherapy is an independent prognosis factor for osteosarcoma. Due to the potential risk of selection bias, performance bias and publication bias, the evidence is not b enough to judge whether high-dose chemotherapy is better than moderate-dose chemotherapy in the treatment of osteosarcoma. Our conclusion suggests that large-scale randomized trials should be performed.

Citation： LI Tongxiang,BAI Jingping,XILIN Boleri,JIANG Renbing,HE Zusheng,HUANG Weimin,WU Taixiang. High-dose Versus Moderate-dose Chemotherapy for Osteosarcoma: A Systematic Review. Chinese Journal of Evidence-Based Medicine, 2006, 06(11): 826-832. doi: Copy

1.	徐万鹏, 冯传汉. 主编. 骨科肿瘤学. 第1版. 北京: 民军医出版社; 2001. 179.
2.	Xu WP, Feng CH. Orthopaedic Oncology. First Edition. Beijing: Peoples Military Medical Publisher; 2001. 179.
3.	Horfman HD, Czerniak B. Bone tumors. St Louis: Mosby; 1998: 32–33.
4.	Saeter G, Oliveira J, Bergh J, ESMO Guidelines Task Force. ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of osteosarcoma. Ann Oncol, 2005; 16 (Suppl 1): 73–74.
5.	Dahlin D, Coventry M. Osteogenic sarcoma: a study of six hundred cases. J Bone Joint Surg Am, 1975; 57(3): 397–404.
6.	Enneking WF. An abbreviated history of orthopaedic oncology in North America. Clin Orthop Relat Res, 2000; (374): 115–124.
7.	Goorin AM, Abelson HT, Frei III E. Osteosarcoma: Fifteen years later. N Engl J Med, 1985; 313(26): 1637–1642.
8.	Campanacci M, Bacci G, Bertoni F, et al. The treatment of osteosarcoma of the extremities: twenty years’ experience at theIstituto Ortopedico Rizzoli. Cancer, 1981; 48(7): 1569–1581.
9.	Hudson M, Jaffe MR, Jaffe N, et al. Pediatric osteosarcoma: therapeutic strategies, results and alprognostic factors derived from a 10-year experience. J Clin Oncol, 1990; 8(12): 1988–1997.
10.	Jaffe N. Adjuvant chemotherapy in osteogenic sarcoma. J Clin Oncol, 1984; 2(10): 1179–1181.
11.	Meyers PA, Heller G, Healey J, et al. Chemotherapy for non-metastatic osteosarcoma: the Memorial Sloan-Kettering experience. J Clin Oncol, 1992; 10(1): 5–15.
12.	Eilber F, Giuliano A, Eckardt J, et al. Adjuvant chemotherapy for osteosarcoma: a randomised prospective trial. J Clin Oncol, 1987; 5(1): 21–26.
13.	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. Italian Journal of Orthopaedics & Traumatology, 1988; 14(1): 23–39.
14.	Gaetano B, Cristiana F, Stefano F, et al. Neoadjuvant chemotherapy forosteosarcoma of the extremity: intensification of preoperative treatment does not increase the rate of good histologic response to the primary tumor or improve the final outcome. J Pediatr Hematal Onco, 2003; 25(11): 845–853.
15.	Meyers PA, Gorlick R, Hellr G, et al. Intensification of preoperative chemotherapy for osteogenic sarcoma:rsults of the memorial sloan-kettering (t12) protocol. Journal of Clinical Oncology, 1998; 16(7): 2452–2458.
16.	Bacci G, Gherlinzoni F, Picci P, et al. Adriamycin-methotrexae high dose as verss adriamycin-methotrexae moderate dose as adjuvant chemotherapy for osteosarcoma of the extremities: a randomized study. Eur J Clin Oncol, 1986; 22(11): 1337–1345.
17.	Souhami L, Craft AW, Van der Eijken JW, et al. Randomized trial of two regmens of chemotherapy in operative osteosarcoma: a study of the European osteosarcoma intergroup. Lancet, 1997; 350(9082): 911–917.
18.	Damron TA, Pritchard DJ. Current combined treatment high-grade osteosarcomas. Oncology, 1995; 9(4): 327–343; discussion 343–344, 347–350.
19.	Meyers PA, Gorlick R. Osteosarcoma. Pediatr Clin North Am, 1997; 44(3): 973–989.
20.	Rosen G, Marcove RC, Caparros B, et al. Primary osteogenic sarcoma:the rational for preoperative chemotherapy and delayed surgery. Cancer, 1979; 43(6): 2163–2177.

1. 徐万鹏, 冯传汉. 主编. 骨科肿瘤学. 第1版. 北京: 民军医出版社; 2001. 179.
2. Xu WP, Feng CH. Orthopaedic Oncology. First Edition. Beijing: Peoples Military Medical Publisher; 2001. 179.
3. Horfman HD, Czerniak B. Bone tumors. St Louis: Mosby; 1998: 32–33.
4. Saeter G, Oliveira J, Bergh J, ESMO Guidelines Task Force. ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of osteosarcoma. Ann Oncol, 2005; 16 (Suppl 1): 73–74.
5. Dahlin D, Coventry M. Osteogenic sarcoma: a study of six hundred cases. J Bone Joint Surg Am, 1975; 57(3): 397–404.
6. Enneking WF. An abbreviated history of orthopaedic oncology in North America. Clin Orthop Relat Res, 2000; (374): 115–124.
7. Goorin AM, Abelson HT, Frei III E. Osteosarcoma: Fifteen years later. N Engl J Med, 1985; 313(26): 1637–1642.
8. Campanacci M, Bacci G, Bertoni F, et al. The treatment of osteosarcoma of the extremities: twenty years’ experience at theIstituto Ortopedico Rizzoli. Cancer, 1981; 48(7): 1569–1581.
9. Hudson M, Jaffe MR, Jaffe N, et al. Pediatric osteosarcoma: therapeutic strategies, results and alprognostic factors derived from a 10-year experience. J Clin Oncol, 1990; 8(12): 1988–1997.
10. Jaffe N. Adjuvant chemotherapy in osteogenic sarcoma. J Clin Oncol, 1984; 2(10): 1179–1181.
11. Meyers PA, Heller G, Healey J, et al. Chemotherapy for non-metastatic osteosarcoma: the Memorial Sloan-Kettering experience. J Clin Oncol, 1992; 10(1): 5–15.
12. Eilber F, Giuliano A, Eckardt J, et al. Adjuvant chemotherapy for osteosarcoma: a randomised prospective trial. J Clin Oncol, 1987; 5(1): 21–26.
13. 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. Italian Journal of Orthopaedics & Traumatology, 1988; 14(1): 23–39.
14. Gaetano B, Cristiana F, Stefano F, et al. Neoadjuvant chemotherapy forosteosarcoma of the extremity: intensification of preoperative treatment does not increase the rate of good histologic response to the primary tumor or improve the final outcome. J Pediatr Hematal Onco, 2003; 25(11): 845–853.
15. Meyers PA, Gorlick R, Hellr G, et al. Intensification of preoperative chemotherapy for osteogenic sarcoma:rsults of the memorial sloan-kettering (t12) protocol. Journal of Clinical Oncology, 1998; 16(7): 2452–2458.
16. Bacci G, Gherlinzoni F, Picci P, et al. Adriamycin-methotrexae high dose as verss adriamycin-methotrexae moderate dose as adjuvant chemotherapy for osteosarcoma of the extremities: a randomized study. Eur J Clin Oncol, 1986; 22(11): 1337–1345.
17. Souhami L, Craft AW, Van der Eijken JW, et al. Randomized trial of two regmens of chemotherapy in operative osteosarcoma: a study of the European osteosarcoma intergroup. Lancet, 1997; 350(9082): 911–917.
18. Damron TA, Pritchard DJ. Current combined treatment high-grade osteosarcomas. Oncology, 1995; 9(4): 327–343; discussion 343–344, 347–350.
19. Meyers PA, Gorlick R. Osteosarcoma. Pediatr Clin North Am, 1997; 44(3): 973–989.
20. Rosen G, Marcove RC, Caparros B, et al. Primary osteogenic sarcoma:the rational for preoperative chemotherapy and delayed surgery. Cancer, 1979; 43(6): 2163–2177.

Chinese Journal of Evidence-Based Medicine

High-dose Versus Moderate-dose Chemotherapy for Osteosarcoma: A Systematic Review

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