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Analysis of chemotherapy dosage and dosage intensity and survival outcomes of high-grade osteosarcoma patients younger than 40 years.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Sun, Lingling Li, Yingjun Li, Hengyuan Zhang, Jian Li, Binghao Ye, Zhaoming
Description	Country affiliation: China Author Affiliation: Sun L ( Department of Orthopaedics, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.); Li Y ( Department of Epidemiology and Health Statistics, School of Medicine, Zhejiang University, Hangzhou, China.); Li H ( Department of Orthopaedics, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.); Zhang J ( Department of Orthopaedics, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.); Li B ( Department of Orthopaedics, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.); Ye Z ( Department of Orthopaedics, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. Electronic address: yezhaoming123@gmail.com.)
Abstract	BACKGROUND: Chemotherapy is essential for long-term survival of osteosarcoma patients. However, the impact of dosage and dosage intensity (DI) of chemotherapeutic agents on patients with high-grade osteosarcoma is largely unknown. OBJECTIVE: The object of this study was to evaluate the influence of these dosage-related variables on treatment outcomes in terms of event-free survival (EFS). METHODS: PubMed was searched for relevant English-language articles. Two reviewers extracted data independently. Sufficient data were presented to calculate the planned total dosage and DI for doxorubicin, cisplatin, ifosfamide, and methotrexate. Univariate analysis and partial regression analysis were performed to determine the association of 5-year EFS and the planned total dosage and DI of each drug. RESULTS: Seventeen studies comprising 23 trial arms met the inclusion criteria. The analysis recruited a total of 2257 patients. The study period ranged from 1976 to 2006. Using univariate analysis, the planned dosage and DI of methotrexate and ifosfamide correlated with better 5-year EFS (P = 0.001 for methotrexate dosage; P = 0.030 for ifosfamide dosage; P < 0.001 for methotrexate DI; and P = 0.033 for ifosfamide DI). There was a trend toward worse 5-year EFS with increase of doxorubicin DI (P = 0.055). Based on the partial regression analysis, the association of doxorubicin DI and ifosfamide dosage and DI with EFS became no longer statistically significant, and the planned total dosage and DI of methotrexate remained significantly correlated with better 5-year EFS (P = 0.001 and P = 0.004, respectively). CONCLUSIONS: We observed a correlation of higher planned methotrexate total dosage and DI with better treatment outcomes in osteosarcoma patients. The present study showed that methotrexate dosage and DI were important predictors of the clinical outcomes and provided the rationale of high-dosage methotrexate in the context of multi-agent chemotherapy.
File Format	HTM / HTML
ISSN	01492918
Issue Number	4
Volume Number	36
e-ISSN	1879114X
Journal	Clinical Therapeutics
Language	English
Publisher	Elsevier
Publisher Date	2014-04-01
Publisher Place	United States
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Pharmacology Antineoplastic Agents Administration & Dosage Antineoplastic Combined Chemotherapy Protocols Bone Neoplasms Drug Therapy Osteosarcoma Adolescent Adult Analysis Of Variance Mortality Pathology Cisplatin Disease-free Survival Doxorubicin Female Humans Ifosfamide Male Methotrexate Neoplasm Grading Treatment Outcome Journal Article Meta-analysis Research Support, Non-u.s. Gov't Review
Content Type	Text
Resource Type	Article
Subject	Pharmacology Pharmacology (medical)

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