Fouladi Maryam, Gururangan Sri, Moghrabi Albert, Phillips Peter, Gronewold Lindsey, Wallace Dana, Sanford Robert A, Gajjar Amar, Kun Larry E, Heideman Richard
Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Cancer. 2009 Jul 15;115(14):3243-53. doi: 10.1002/cncr.24362.
A carboplatin-based chemotherapy regimen was used as primary postoperative therapy in infants with central nervous system (CNS) tumors to limit renal and ototoxicity and to target systemic exposure.
Fifty-three patients aged <age 3 years with embryonal CNS tumor medulloblastoma (n = 20), ependymoma (EP, n = 21), choroid plexus carcinoma (CPCA, n = 5), and primitive embryonal neoplasms including atypical teratoid rhabdoid tumors (n = 7) were treated with cyclophosphamide, etoposide, and carboplatin. Radiation therapy was used only for residual disease at the end of chemotherapy or disease progression.
The response rate after 2 cycles of chemotherapy was 34% (complete response, 13.8%; partial response, 20.7%). Myelosuppression was the dominant toxicity; 2 patients had toxic deaths related to thrombocytopenia with trauma. The 5-year overall survival (OS) was 49% +/- 7%, and the progression-free survival (PFS) was 31% +/- 7%, with a median follow-up of 11.4 years (range, 5.2-15.0 years). For medulloblastoma, the 5-year PFS was 26% +/- 9%; for EP it was 33% +/- 10%; for CPCA it was 80% +/- 18%; and for primitive neuroectodermal and atypical teratoid rhabdoid tumors it was 0%. Localized EP patients with gross total resection who did not undergo radiotherapy had a 5-year PFS of 57% +/- 17% and OS of 71% +/- 16%. Two patients developed late second malignancies; 1 was associated with germline p53 mutation.
The results confirm that carboplatin has similar activity to cisplatin in otherwise similar regimens. Five-year survival data are comparable to those reported in other recent studies, including high-dose chemotherapy studies. Of note is the marked activity in CPCA and gross totally resected EP.
基于卡铂的化疗方案被用作中枢神经系统(CNS)肿瘤婴儿的术后主要治疗方法,以限制肾毒性和耳毒性,并针对全身暴露情况。
53例年龄小于3岁的患有胚胎性CNS肿瘤的患者,包括髓母细胞瘤(n = 20)、室管膜瘤(EP,n = 21)、脉络丛癌(CPCA,n = 5)以及包括非典型畸胎样横纹肌样肿瘤在内的原始胚胎性肿瘤(n = 7),接受了环磷酰胺、依托泊苷和卡铂治疗。放射治疗仅用于化疗结束时的残留疾病或疾病进展。
2个周期化疗后的缓解率为34%(完全缓解,13.8%;部分缓解,20.7%)。骨髓抑制是主要毒性;2例患者因血小板减少伴创伤导致毒性死亡。5年总生存率(OS)为49%±7%,无进展生存率(PFS)为31%±7%,中位随访时间为11.4年(范围,5.2 - 15.0年)。对于髓母细胞瘤,5年PFS为26%±9%;对于EP为33%±10%;对于CPCA为80%±18%;对于原始神经外胚层和非典型畸胎样横纹肌样肿瘤为0%。未接受放疗的行大体全切的局限性EP患者5年PFS为57%±17%,OS为71%±16%。2例患者发生晚期第二原发恶性肿瘤;1例与种系p53突变有关。
结果证实,在其他方面相似的方案中,卡铂与顺铂具有相似的活性。5年生存数据与其他近期研究(包括高剂量化疗研究)报道的数据相当。值得注意的是CPCA和大体全切的EP有显著活性。