Boulad F, Kernan N A, LaQuaglia M P, Heller G, Lindsley K L, Rosenfield N S, Abramson S J, Gerald W L, Small T N, Gillio A P, Gulati S C, O'Reilly R J, Ghavimi F
Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
J Clin Oncol. 1998 May;16(5):1697-706. doi: 10.1200/JCO.1998.16.5.1697.
To improve response and survival rates in patients with high-risk rhabdomyosarcoma (RMS), extraosseous Ewing's sarcoma, and undifferentiated sarcoma, we used a short course of induction with multi-agent chemotherapy, hyperfractionated radiotherapy, and surgery when possible. Consolidation was with intensive chemotherapy and autologous bone marrow transplantation (ABMT).
Twenty-six patients (21 with RMS, three with undifferentiated sarcoma, and two with extraosseous Ewing's sarcoma) were entered onto the protocol between June 1990 and March 1994. Induction consisted of ifosfamide, etoposide, doxorubicin, dactinomycin, cyclophosphomide, and vincristine, and a split course of hyperfractionated radiotherapy. Patients who attained a complete response (CR) or good partial response (GPR) received consolidation with high-dose melphalan and etoposide followed by ABMT.
Of 26 previously untreated patients 19 (73%) achieved a CR (n=13) or GPR (n=6) at the completion of induction and underwent ABMT. Two-year overall survival (OS) was 56% (95% confidence interval [CI], 36% to 76%) and progression-free survival (PFS) was 53% for the whole group (95% CI, 33% to 73%).
Consolidation of response by myeloablative chemotherapy was well tolerated. Split-course hyperfractionated radiotherapy did not increase the rate of local control. The results of this short-course therapy were comparable to previous therapies of 1 to 2 years' duration. Induction and consolidation chemotherapy, as well as radiation dose, could be further intensified, since no death due to toxicity occurred among these patients.
为提高高危横纹肌肉瘤(RMS)、骨外尤文肉瘤和未分化肉瘤患者的缓解率和生存率,我们采用了短期诱导化疗、超分割放疗,并尽可能进行手术。巩固治疗采用强化化疗和自体骨髓移植(ABMT)。
1990年6月至1994年3月,26例患者(21例RMS、3例未分化肉瘤、2例骨外尤文肉瘤)进入本方案。诱导治疗包括异环磷酰胺、依托泊苷、多柔比星、放线菌素D、环磷酰胺和长春新碱,以及超分割放疗的分段疗程。达到完全缓解(CR)或良好部分缓解(GPR)的患者接受大剂量美法仑和依托泊苷巩固治疗,随后进行ABMT。
26例未经治疗的患者中,19例(73%)在诱导治疗结束时达到CR(n = 13)或GPR(n = 6)并接受了ABMT。全组两年总生存率(OS)为56%(95%置信区间[CI],36%至76%),无进展生存率(PFS)为53%(95%CI,33%至73%)。
清髓性化疗巩固缓解效果耐受性良好。分段超分割放疗未提高局部控制率。这种短期治疗的结果与之前1至2年疗程的治疗相当。由于这些患者中未发生因毒性导致的死亡,诱导和巩固化疗以及放疗剂量可进一步强化。