Patel Shreyaskumar R, Papadopolous Nicholas, Raymond A Kevin, Donato Michele, Seong Chu-Myong, Yasko Alan W, Lewis Valerae O, Lin Patrick P, Champlin Richard, Benjamin Robert S
The Sarcoma Center, The University of Texas M.D. Anderson Cancer Center, PO Box 450, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Cancer. 2004 Jul 1;101(1):156-63. doi: 10.1002/cncr.20317.
The authors evaluated the efficacy and toxicity of cisplatin, ifosfamide, and doxorubicin with peripheral blood stem cell (PBSC) support in adult patients with osteosarcomas and variants with a poor prognosis.
Between December 1994 and January 2001, 37 patients (20 males and 17 females) with a median age of 38 years (range, 18-63 years) entered the study. Ten patients had pelvic osteosarcomas (OS), 6 had malignant fibrous histiocytomas, 5 had metastatic OS, and 16 had miscellaneous histologies. The authors used doxorubicin (60-75 mg/m(2)) and ifosfamide (10 g/m(2)) followed by granulocyte-colony-stimulating factor (G-CSF) (5 microg/kg twice per day) for mobilization of PBSC, collected at a median of 12 days (range, 10-14 days). Three cycles with cisplatin (120 mg/m(2)), ifosfamide (10 g/m(2)), and doxorubicin (75 mg/m(2)), given 28 days apart, were planned followed by PBSC (2-4 x 10(6) CD34-positive cells/kg) infusion plus G-CSF.
Patients received a median of three cycles (range, one to three cycles) in addition to the mobilizing cycle. The median PBSC collection was 17.5 x 10(6)/kg (range, 13.2-90.8 x 10(6)/kg) with a median of 1 apheresis (range, 1-2 aphereses). Twenty-eight patients underwent surgery, 10 achieved 95-100% necrosis, and 4 achieved 90-94% necrosis. Six patients required early discontinuation of therapy due to toxicities, two patients developed progressive disease, and one patient was deemed unresectable. The median time to progression (TTP) and overall survival by Kaplan-Meier estimates for all 37 patients was 19 months and 49 months, respectively.
The authors accomplished the objective of improving the rate of necrosis with intensification of preoperative therapy. However, TTP and survival rates remained poor. The toxicity profile of this regimen is prohibitive and alternative strategies need to be investigated.
作者评估了顺铂、异环磷酰胺和阿霉素联合外周血干细胞（PBSC）支持疗法对成年骨肉瘤患者及预后不良变体的疗效和毒性。
1994年12月至2001年1月期间，37例患者（20例男性和17例女性）进入研究，中位年龄38岁（范围18 - 63岁）。10例患者患有骨盆骨肉瘤（OS），6例患有恶性纤维组织细胞瘤，5例患有转移性OS，16例具有其他组织学类型。作者使用阿霉素（60 - 75mg/m²）和异环磷酰胺（10g/m²），随后使用粒细胞集落刺激因子（G - CSF）（5μg/kg，每日两次）动员PBSC，中位采集时间为12天（范围10 - 14天）。计划每28天给予顺铂（120mg/m²）、异环磷酰胺（10g/m²）和阿霉素（75mg/m²）三个周期，随后输注PBSC（2 - 4×10⁶个CD34阳性细胞/kg）并加用G - CSF。
除动员周期外，患者接受的中位周期数为三个周期（范围一至三个周期）。PBSC的中位采集量为17.5×10⁶/kg（范围13.2 - 90.8×10⁶/kg），中位单采次数为1次（范围1 - 2次）。28例患者接受了手术，10例坏死率达到95 - 100%，4例坏死率达到90 - 94%。6例患者因毒性反应需要提前终止治疗，2例患者疾病进展，1例患者被认为无法切除。根据Kaplan - Meier估计，所有37例患者的中位进展时间（TTP）和总生存期分别为19个月和49个月。
作者通过强化术前治疗实现了提高坏死率的目标。然而，TTP和生存率仍然较差。该方案的毒性令人望而却步，需要研究替代策略。
