Crist W, Gehan E A, Ragab A H, Dickman P S, Donaldson S S, Fryer C, Hammond D, Hays D M, Herrmann J, Heyn R
Childrens Cancer Group, Arcadia CA.
J Clin Oncol. 1995 Mar;13(3):610-30. doi: 10.1200/JCO.1995.13.3.610.
The ultimate goal of the Third Intergroup Rhabdomyosarcoma Study (IRS-III, 1984 to 1991) was to improve treatment outcome in children with rhabdomyosarcoma through clinical trials comparing risk-based protocols of surgery and multiagent chemotherapy, with or without irradiation.
One thousand sixty-two previously untreated, eligible patients who were entered onto the study after surgery were randomized or assigned to treatment by clinical group (I through IV), histology (unfavorable or favorable), and site of the primary tumor. Initial responses, progression-free survival (PFS), and survival (S) were the end points used in comparisons between randomized groups and between patients treated in IRS-III and IRS-II (1978 to 1984).
The overall outcome of therapy in IRS-III was significantly better than in IRS-II (5-year PFS, 65% +/- 2% v 55% +/- 2%; P < .001 by stratified testing). Patients with group I favorable-histology tumors fared as well on a 1-year regimen of vincristine and dactinomycin (VA), as did a comparable group treated with VA plus cyclophosphamide (C) (5-year PFS, 83% +/- 3% v 76% +/- 4%; P = .18). Results for patients with group II favorable-histology tumors, excluding orbit, head, and paratesticular sites, were inconclusive regarding the benefit from addition of doxorubicin (ADR) to VA. Patients with group III tumors, excluding those in special pelvic, orbit, and other selected nonparameningeal head sites, fared much better on the more intensive regimens of IRS-III than on pulsed VAC or VAC-VADRC in IRS-II (5-year PFS estimates, 62% +/- 3% v 52% +/- 3%; P < .01); however, there were no significant differences in outcome among the groups treated in IRS-III. Patients with metastatic disease at diagnosis (clinical group IV) did not benefit significantly from the more complex therapies evaluated in IRS-III.
Intensification of therapy for most patients in IRS-III, using a risk-based study design, significantly improved treatment outcome overall. The largest gain from this strategy was realized in patients with gross residual tumor after biopsy (clinical group III). It was also possible to decrease therapy for selected patient subsets without compromising survival.
第三届横纹肌肉瘤协作组研究（IRS-III，1984年至1991年）的最终目标是通过临床试验比较基于风险的手术和多药化疗方案（有或无放疗）来改善横纹肌肉瘤患儿的治疗效果。
1062例术后进入该研究的既往未接受治疗的合格患者，根据临床分组（I至IV组）、组织学类型（预后不良或预后良好）和原发肿瘤部位进行随机分组或分配治疗。初始反应、无进展生存期（PFS）和总生存期（S）是用于随机分组之间以及IRS-III组和IRS-II组（1978年至1984年）治疗患者之间比较的终点指标。
IRS-III的总体治疗效果明显优于IRS-II（5年PFS，65%±2%对55%±2%；分层检验P<0.001）。I组预后良好组织学类型肿瘤患者接受长春新碱和放线菌素D（VA）1年方案治疗的效果，与接受VA加环磷酰胺（C）治疗的类似组相当（5年PFS，83%±3%对76%±4%；P = 0.18）。对于II组预后良好组织学类型肿瘤患者（不包括眼眶、头部和睾丸旁部位），在VA方案中加用阿霉素（ADR）是否有益尚无定论。III组肿瘤患者（不包括特殊盆腔、眼眶和其他选定的非脑膜旁头部部位），在IRS-III更强化的方案下的治疗效果比IRS-II的脉冲VAC或VAC-VADRC方案好得多（5年PFS估计值，62%±3%对52%±3%；P<0.01）；然而，IRS-III治疗的各组之间在治疗效果上没有显著差异。诊断时患有转移性疾病的患者（临床IV组）没有从IRS-III评估的更复杂治疗中显著获益。
IRS-III中大多数患者采用基于风险的研究设计强化治疗，总体上显著改善了治疗效果。该策略最大的获益体现在活检后有肉眼残留肿瘤的患者（临床III组）。对于选定的患者亚组，在不影响生存的情况下减少治疗也是可行的。
