Palenzuela Gilles, Schiffler Camille, Frappaz Didier, Peyrl Andreas, Gerber Nicolas U, Kortmann Rolf-Dieter, Philippe Michael, Zimmermann Martin, Murray Matthew J, Nicholson James C, Calaminus Gabriele, Faure-Conter Cécile
University Hospital, Department of Paediatric Haematology and Oncology, Montpellier, France.
Department of Biostatistics, Centre Léon Bérard, Lyon, France.
Front Oncol. 2024 Jul 15;14:1421418. doi: 10.3389/fonc.2024.1421418. eCollection 2024.
SIOP-CNS-GCT-II European trial was opened for the treatment of patients of any age with central nervous system germ cell tumour (CNS-GCT). Four courses of pre-irradiation chemotherapy were delivered. The influence of patient age on chemotherapy related acute toxicity (CRAT) was assessed.
CRAT was analysed according to age-groups: children (aged ≤11 years), adolescents (aged 12-17 years), adults (aged ≥18 years) and to chemotherapy type: CarboPEI (alternating etoposide-carboplatin/etoposide-ifosfamide) for non-metastatic germinoma; PEI (cisplatin-etoposide-ifosfamide) for standard-risk non-germinomatous GCT (NGGCT); PEI and high-dose PEI (HD-PEI), for high-risk or poorly responsive NGGCTs.
296 patients were assessable for CRAT: 105 children, 121 adolescents, 70 adults (max age: 41 years). Median cumulative doses/m² of chemotherapy were similar among age-groups. The proportion of germinoma over NGGCT (and accordingly use of CarboPEI chemotherapy) was higher in the adult groups (79%) versus the other two groups (62%). Delay in chemotherapy ≥7 days was noticed in 27%, 38%, and 19% of children, adolescents, and adults, respectively. Grade ≥3 haematological and non-haematological adverse events (AEs) were observed in 94%/31%, 97%/36%, and 77%/21% of children, adolescents, and adults, respectively. No toxic death was reported. Grade ≥3 AEs and delayed chemotherapies were significantly rarer in adults when compared with adolescents, even when adjusted on chemotherapy type: odds ratio: 0.1 [95%CI 0.02-0.4], and 0.2 [95%CI 0.1-0.4] in the group treated with CarboPEI.
Adult patients can be treated safely with a chemotherapy intensive protocol, with even less toxicity than that observed in adolescents. Further work is required to understand age-related differences regarding toxicity.
SIOP-CNS-GCT-II欧洲试验开启，用于治疗任何年龄的中枢神经系统生殖细胞肿瘤（CNS-GCT）患者。进行了四个疗程的放疗前化疗。评估了患者年龄对化疗相关急性毒性（CRAT）的影响。
根据年龄组分析CRAT：儿童（年龄≤11岁）、青少年（年龄12 - 17岁）、成人（年龄≥18岁），并根据化疗类型分析：非转移性生殖细胞瘤采用CarboPEI（交替使用依托泊苷-卡铂/依托泊苷-异环磷酰胺）；标准风险非生殖细胞性生殖细胞瘤（NGGCT）采用PEI（顺铂-依托泊苷-异环磷酰胺）；高风险或反应不佳的NGGCT采用PEI和高剂量PEI（HD-PEI）。
296例患者可评估CRAT：105例儿童、121例青少年、70例成人（最大年龄：41岁）。各年龄组化疗的中位累积剂量/平方米相似。成人组中生殖细胞瘤相对于NGGCT的比例（相应地使用CarboPEI化疗的比例）高于其他两组（分别为79%和62%）。化疗延迟≥7天的情况在儿童、青少年和成人中分别为27%、38%和19%。≥3级血液学和非血液学不良事件（AE）在儿童、青少年和成人中分别观察到94%/31%、97%/36%和77%/21%。未报告毒性死亡。与青少年相比，成人中≥3级AE和化疗延迟明显少见，即使在根据化疗类型进行调整后也是如此：使用CarboPEI治疗的组中，比值比分别为0.1 [95%CI：0.02 - 0.4]和0.2 [95%CI：0.1 - 0.4]。
成人患者可以安全地接受强化化疗方案治疗，其毒性甚至低于青少年。需要进一步开展工作以了解与年龄相关的毒性差异。
