Arndt C, Tefft M, Gehan E, Anderson J, Jenson M, Link M, Donaldson S, Breneman J, Wiener E, Webber B, Maurer H
Mayo Clinic, Rochester, MN 55905, USA.
J Pediatr Hematol Oncol. 1997 Mar-Apr;19(2):124-9. doi: 10.1097/00043426-199703000-00005.
The purpose of this study was to determine the feasibility, toxicity, and early response of patients with clinical group III rhabdomyosarcoma (RMS) to a chemotherapy regimen of etoposide (ETOP), ifosfamide (IFOS), and vincristine (VCR) with hyperfractionated radiation therapy (XRT).
Sixty-eight patients aged < 21 years, previously untreated, with clinical group III RMS or undifferentiated sarcoma with normal organ function were eligible for this study. Chemotherapy was as follows: weeks 0-8: IFOS 1.8 g/m2/day X 5 days every 3 weeks X 3 (with mesna), ETOP 100 mg/m2/day X 5 days every 3 weeks X 3, and VCR 1.5 mg/m2/week X 9; weeks 9-16: hyperfractionated XRT (except patients with parameningeal tumors with meningeal extension, who received XRT on day 0), IFOS/mesna weeks 9, 12, 16, and VCR weeks 9, 10, 11, 12, 16; weeks 20-99; IFOS/mesna q 3 weeks X 2, ETOP q 3 weeks X 2, and VCR weekly X 6 weeks. Four drug cycles were repeated every 9 weeks, beginning at week 29. In January 1991, the duration of therapy was reduced to 12 courses due to emerging evidence of IFOS-induced renal tubular dysfunction.
Of the 62 patients evaluable for response, 45 (73%) achieved a complete response. There were three fatal toxicities due to infection. Life-threatening neutropenia was seen in 55 of 60 patients, and life-threatening infections occurred in 27 of 60 patients. Twenty-five patients (42%) developed some degree of neurotoxicity from vincristine. Eleven patients (18%) developed nephrotoxicity, 7 cases of which were severe; 6 of the 11 patients who developed nephrotoxicity were < 2 years old.
This pilot study had toxicity and response rates comparable to the other two Intergroup Rhabdomyosarcoma Study (IRS)-IV pilot trials of vincristine-actinomycin-cyclophosphamide and vincristine-actinomycin-ifosfamide and is, therefore, being evaluated in the current IRS randomized trial. Due to the high incidence of life-threatening neutropenia and infections, the use of growth factors is now routine. Five of 11 patients who developed nephrotoxicity did so after more than eight courses of IFOS; therefore, the current randomized trial limits IFOS to a total of eight courses.
本研究旨在确定临床Ⅲ组横纹肌肉瘤（RMS）患者接受依托泊苷（ETOP）、异环磷酰胺（IFOS）和长春新碱（VCR）联合超分割放射治疗（XRT）化疗方案的可行性、毒性及早期反应。
68例年龄＜21岁、未曾接受过治疗、临床诊断为Ⅲ组RMS或器官功能正常的未分化肉瘤患者符合本研究条件。化疗方案如下：第0 - 8周：IFOS 1.8 g/m²/天，每3周连用5天，共3次（同时使用美司钠）；ETOP 100 mg/m²/天，每3周连用5天，共3次；VCR 1.5 mg/m²/周，共9次。第9 - 16周：超分割XRT（除有脑膜扩展的颅底肿瘤患者在第0天接受XRT外），第9、12、16周使用IFOS/美司钠，第9、10、11、12、16周使用VCR。第20 - 99周：IFOS/美司钠每3周1次，共2次；ETOP每3周1次，共2次；VCR每周1次，共6周。从第29周开始，每9周重复4个周期的化疗。1991年1月，由于有新证据表明IFOS可导致肾小管功能障碍，治疗疗程减至12个疗程。
62例可评估反应的患者中，45例（73%）达到完全缓解。有3例因感染导致致命毒性反应。60例患者中有55例出现危及生命的中性粒细胞减少，60例患者中有27例发生危及生命的感染。25例患者（42%）因长春新碱出现一定程度的神经毒性。11例患者（18%）出现肾毒性，其中7例严重；11例发生肾毒性的患者中有6例年龄＜2岁。
本初步研究的毒性和反应率与横纹肌肉瘤研究组（IRS）-IV另外两项长春新碱-放线菌素-环磷酰胺及长春新碱-放线菌素-异环磷酰胺的初步试验相当，因此正在当前的IRS随机试验中进行评估。由于危及生命的中性粒细胞减少和感染发生率高，目前常规使用生长因子。11例发生肾毒性的患者中有5例是在接受超过8个疗程的IFOS治疗后出现的；因此，当前的随机试验将IFOS的总疗程限制为8个疗程。
