Rosen G, Caparros B, Huvos A G, Kosloff C, Nirenberg A, Cacavio A, Marcove R C, Lane J M, Mehta B, Urban C
Cancer. 1982 Mar 15;49(6):1221-30. doi: 10.1002/1097-0142(19820315)49:6<1221::aid-cncr2820490625>3.0.co;2-e.
Since June 1978, 57 patients with primary osteogenic sarcoma of an extremity were treated with high-dose methotrexate (HDMTX) and citrovorum factor rescue (CFR), Adriamycin, and the combination of bleomycin, cyclophosphamide and dactinomycin (BCD) given for 4-16 weeks prior to definitive surgery. Histologic examination of the resected primary tumor determined the effect of preoperative chemotherapy with many primary tumors showing greater than 90% tumor necrosis attributable to preoperative chemotherapy. All patients having this favorable effect of chemotherapy on the primary tumor were continued on the same chemotherapy regimen postoperatively (regimen B). However, in those patients not having a good effect of preoperative chemotherapy on the primary tumor, HDMTX with CFR was subsequently deleted from their postoperative chemotherapy and they were placed on a regimen containing cisplatinum at the dose of 120mg/M2 with mannitol diuresis combined with Adriamycin in addition to BCD (regimen A). In the current study, 35 of the 57 patients did not demonstrate a good effect of chemotherapy on the primary tumor and were assigned to regimen A postoperatively. Of these 35 patients, 32 (91%) have remained continuously free of recurrent or metastatic disease from 6-34 months following the start of therapy. Among the 22 remaining patients having a good histologic response and treated with regimen B postoperatively, there has been only one relapse in a patient who had a local recurrence in the area of an inadequately resected primary tumor three months after the cessation of chemotherapy. Thus, 53 of 57 patients (93%) are continuously with no evidence of recurrent or metastatic disease from 6-35 months (median, 20 months) from the start of treatment. This study demonstrates the value of thorough histologic examination in predicting survival in responding patients and in helping identify patients whose disease-free survival rate can be substantially increased if they are given alternative postoperative adjuvant chemotherapy after failing to have a good response to preoperative chemotherapy. This individualized chemotherapeutic strategy has yielded the highest disease-free survival rate reported to date for osteogenic sarcoma.
自1978年6月起，57例肢体原发性骨肉瘤患者接受了大剂量甲氨蝶呤（HDMTX）和亚叶酸钙解救（CFR）、阿霉素以及博来霉素、环磷酰胺和放线菌素D联合方案（BCD）治疗，在确定性手术前给药4 - 16周。对切除的原发性肿瘤进行组织学检查，以确定术前化疗的效果，许多原发性肿瘤显示术前化疗导致肿瘤坏死率超过90%。所有原发性肿瘤化疗效果良好的患者术后继续采用相同的化疗方案（方案B）。然而，对于那些术前化疗对原发性肿瘤效果不佳的患者，术后化疗中随后停用了HDMTX和CFR，并将他们置于含顺铂（剂量为120mg/M²）、甘露醇利尿联合阿霉素以及BCD的方案中（方案A）。在本研究中，57例患者中有35例术前化疗对原发性肿瘤效果不佳，术后被分配至方案A。在这35例患者中，32例（91%）自治疗开始后6 - 34个月持续无复发或转移疾病。在其余22例组织学反应良好且术后接受方案B治疗的患者中，仅有1例患者在化疗停止三个月后，在原发性肿瘤切除不充分的区域出现局部复发。因此，57例患者中有53例（93%）自治疗开始后6 - 35个月（中位时间20个月）持续无复发或转移疾病证据。本研究证明了全面组织学检查在预测反应性患者生存以及帮助识别那些术前化疗效果不佳但术后给予替代辅助化疗可显著提高无病生存率的患者方面的价值。这种个体化化疗策略产生了迄今为止骨肉瘤报告的最高无病生存率。
