Zalupski Mark M, Rankin Cathryn, Ryan James R, Lucas David R, Muler Jeffrey, Lanier Keith S, Budd George Thomas, Biermann J Sybil, Meyers Frederick J, Antman Karen
Department of Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, USA.
Cancer. 2004 Feb 15;100(4):818-25. doi: 10.1002/cncr.20021.
The objective of this study was to estimate the time to treatment failure and survival rate of the three-drug combination of doxorubicin, cisplatin, and ifosfamide as primary and postoperative, adjunctive treatment for teenagers and adults with osteosarcoma (OS).
Sixty-three eligible patients with nonmetastatic OS of the extremities were registered from 24 institutions from February, 1992 through December, 1996. Chemotherapy was comprised of doxorubicin at a dose of 75 mg/m2 and cisplatin at a dose of 120 mg/m2, alternating with doxorubicin at a dose of 50 mg/m2 and ifosfamide at a dose of 8 g/m2. Four cycles were given prior to surgical resection, and four cycles were given after surgery. Outcome measures included the time to treatment failure, overall survival, toxicity, and centralized assessment of tumor necrosis.
Thirty-one of 63 eligible patients died, for a 5-year overall survival rate of 58% (95% confidence interval [95% CI], 46-71%). The median time to treatment failure was 19 months (95% CI, 12-41 months). A good pathologic response (> or = 90% necrosis) to neoadjuvant chemotherapy was observed in 48% of patients who underwent surgery. There was no correlation noted between response to neoadjuvant chemotherapy and patient outcome. Grade 4 hematologic toxicities were frequent (89%), although serious nonhematologic toxicities other than nausea and emesis were uncommon.
The regimen and schedule used in the current study did not improve outcomes compared with prior trials of doxorubicin and cisplatin alone. New, more effective drugs are needed for the treatment of patients with OS. The identification and utilization of molecular markers to predict outcome and response to therapy would facilitate clinical management, limiting exposure to toxic therapies for patients with favorable molecular profiles and identifying those patients who may fail with current approaches as candidates for clinical trials.
本研究的目的是评估多柔比星、顺铂和异环磷酰胺三药联合方案作为青少年和成人骨肉瘤（OS）的一线及术后辅助治疗的治疗失败时间和生存率。
1992年2月至1996年12月期间，从24家机构登记了63例符合条件的四肢非转移性骨肉瘤患者。化疗方案为多柔比星剂量75mg/m²和顺铂剂量120mg/m²交替使用，多柔比星剂量50mg/m²和异环磷酰胺剂量8g/m²交替使用。手术切除前给予4个周期，术后给予4个周期。观察指标包括治疗失败时间、总生存率、毒性以及肿瘤坏死的集中评估。
63例符合条件的患者中有31例死亡，5年总生存率为58%（95%置信区间[95%CI]，46 - 71%）。治疗失败的中位时间为19个月（95%CI，12 - 41个月）。48%接受手术的患者对新辅助化疗有良好的病理反应（坏死率≥90%）。新辅助化疗反应与患者预后之间未发现相关性。4级血液学毒性常见（89%），但除恶心和呕吐外的严重非血液学毒性不常见。
与之前单独使用多柔比星和顺铂的试验相比，本研究中使用的方案和疗程并未改善预后。治疗骨肉瘤患者需要新的、更有效的药物。识别和利用分子标志物来预测预后和治疗反应将有助于临床管理，减少对分子特征良好的患者的毒性治疗暴露，并识别那些可能对当前方法治疗失败的患者作为临床试验的候选者。
