Mandell L R, Ghavimi F, Exelby P, Fuks Z
Dept. of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Int J Radiat Oncol Biol Phys. 1988 Jul;15(1):197-203. doi: 10.1016/0360-3016(88)90366-5.
In an attempt to reduce treatment (Rx) related acute toxicity and improve protocol compliance without compromising local control nor overall survival, a Phase II single arm pilot employing alternating intensive multiagent CT and radiotherapy (RT) in children with gross residual or metastatic RMS was begun at Memorial Sloan-Kettering Cancer Center (MSKCC) in 1984. Hyperfractionated radiotherapy (HART) was adopted to allow for timely delivery of both the RT and CT. From July, 1984 through July, 1986 12 patients (pts), aged 2 to 23 yr (median 10 yr) were enrolled on study. CT treatment was delivered over approximately 14 months and included 2 induction and 5 maintenance cycles. The induction CT consisted of two repetitive cycles of Vincristine, Dactinomycin, Cyclophosphamide, Adriamycin, Bleomycin, and Methotrexate; the maintenance CT included the same agents as reduced drug doses. The HART was delivered to the primary site during cycle I of induction at fractions of 150 cGy BID to a total dose of 5400 cGy in 2 courses of 3000 cGy and 2400 cGy, respectively. One hundred percent of patients completed the recommended dose of HART; 0% required unplanned interruptions of HART due to treatment toxicity. With a median follow-up (f/u) from diagnosis of surviving patients of 25 months (range 20-30), the local control rate is 83% (10/12 pts) and the overall survival, 58% (7/12 pts). The median time (MT) to any failure, local or metastatic, is 9 months (mo); and to death, 14 mo. Comparison of results with 12 historical controls with concomitant split-course standard fractionation RT (180-200 cGy/per fraction) and T6 CT during a MSKCC trial from 1975-1984, matched by site and stage of primary, revealed that 9 pts (75%) completed the recommended dose of RT, and 7 pts (58%) required interruptions of RT. With a median f/u of 78 mo (range 34-109), the local control rate was 75% (9/12 pts) and the overall survival, 42% (5/12 pts). The MT to any failure was 14 mo; and to death, 18 mo. These results indicate that the mode of alternating CT and HART (HART T6) as employed in this pilot study is well tolerated. It appears to offer a significant improvement in protocol compliance over previous protocols using concomitant CT and RT without any apparent compromise in local primary control or survival rates with a median f/u suggestive of adequate elapsed time for the appearance of most relapses and deaths in advanced RMS.
为了在不影响局部控制率和总生存率的前提下，降低与治疗（Rx）相关的急性毒性并提高方案依从性，1984年，纪念斯隆 - 凯特琳癌症中心（MSKCC）开展了一项II期单臂试验，对有大块残留或转移性横纹肌肉瘤（RMS）的儿童采用交替强化多药化疗（CT）和放射治疗（RT）。采用超分割放射治疗（HART）以便及时进行放疗和化疗。从1984年7月至1986年7月，12例年龄在2至23岁（中位年龄10岁）的患者入组研究。化疗疗程约14个月，包括2个诱导周期和5个维持周期。诱导化疗由长春新碱、放线菌素D、环磷酰胺、阿霉素、博来霉素和甲氨蝶呤的两个重复周期组成；维持化疗包括相同药物但剂量减少。在诱导治疗的第I周期，对原发部位进行HART，每次剂量为150 cGy，每日2次，分两个疗程，分别给予3000 cGy和2400 cGy，总剂量达5400 cGy。100%的患者完成了推荐剂量的HART；0%的患者因治疗毒性需要对HART进行计划外中断。存活患者从诊断起的中位随访时间（f/u）为25个月（范围20 - 30个月），局部控制率为83%（10/12例患者），总生存率为58%（7/12例患者）。出现任何局部或远处转移失败的中位时间（MT）为9个月（mo）；死亡的中位时间为14个月。将这些结果与1975 - 1984年MSKCC一项试验中的12例历史对照患者进行比较，这些对照患者采用同步分割标准分次放疗（每次180 - 200 cGy）及T6化疗方案，按原发部位和分期匹配，结果显示9例（75%）患者完成了推荐剂量的放疗，7例（58%）患者需要中断放疗。中位随访时间为78个月（范围34 - 109个月），局部控制率为75%（9/12例患者），总生存率为42%（5/12例患者）。出现任何失败的MT为14个月；死亡的MT为18个月。这些结果表明，本试验研究中采用的交替化疗和HART（HART T6）模式耐受性良好。与以往采用同步化疗和放疗的方案相比，它在方案依从性方面有显著改善，在局部原发控制或生存率方面没有明显降低，中位随访时间提示有足够时间出现晚期RMS的大多数复发和死亡。
