Carter Thomas J, Milic Marina, McDerra Joanna, McTiernan Anne, Ahmed Mahbubl, Karavasilis Vasilios, Michelagnoli Maria, Windsor Rachael, Seddon Beatrice, Whelan Jeremy, Dileo Palma, Strauss Sandra J
London Sarcoma Service, University College London Hospital, Euston Road, London NW1 2PG, UK.
Research Department of Oncology, UCL Cancer Institute, 70 Huntley Street, London WC1E 6BT, UK.
Cancers (Basel). 2020 Nov 17;12(11):3408. doi: 10.3390/cancers12113408.
Ifosfamide is used to treat soft-tissue sarcoma (STS) and bone sarcoma (BS), with improved efficacy at doses above 9 g/m/cycle. To mitigate treatment-associated toxicity with higher doses, continuous infusional ifosfamide is increasingly used. However, clinical outcome data remain limited. Single-centre retrospective analysis of patients treated with four-weekly infusional ifosfamide (14 g/m/14d) between August 2012 and February 2019 was conducted. Radiological response, progression-free survival (PFS), overall survival (OS) and toxicity were evaluated. Eighty patients were treated-46 with STS and 34 with BS. Patients received a median of three cycles of infusional ifosfamide (1-24). Overall disease control rate (DCR) in STS was 50% (23 of 46 patients), with a median PFS of 3.8 months, and median OS of 13.0 months. In synovial sarcoma (SS), DCR was 80% (12/15), median PFS 8.1 months and median OS 20.9 months. Overall DCR in BS (34 patients) was 30%, with a median PFS of 2.5 months and median OS of 6.2 months. Five patients (6%) stopped treatment due to toxicity alone within the first two cycles. A further 10 patients stopped treatment due to toxicity during later treatment cycles (12%) and 18 patients (23%) required dose modification. Forty-five patients (56%) experienced grade (G) 3/4 haematological toxicity, with 12 episodes of febrile neutropenia and one treatment-related death. Twenty-seven patients (34%) experienced G3/4 non-haematological toxicity, most commonly nausea and vomiting (10, 13%). In summary, infusional ifosfamide has efficacy in STS, most notable in SS. Benefit appears limited in BS. Treatment is associated with toxicity that requires specialist supportive care.
异环磷酰胺用于治疗软组织肉瘤(STS)和骨肉瘤(BS),在剂量高于9 g/m²/周期时疗效更佳。为减轻高剂量治疗相关的毒性,持续输注异环磷酰胺的使用越来越多。然而,临床结局数据仍然有限。对2012年8月至2019年2月期间接受每四周输注一次异环磷酰胺(14 g/m²/14天)治疗的患者进行了单中心回顾性分析。评估了放射学反应、无进展生存期(PFS)、总生存期(OS)和毒性。80例患者接受了治疗,其中46例为STS患者,34例为BS患者。患者接受异环磷酰胺输注的中位数为3个周期(1 - 24个周期)。STS的总体疾病控制率(DCR)为50%(46例患者中的23例),中位PFS为3.8个月,中位OS为13.0个月。在滑膜肉瘤(SS)中,DCR为80%(15例中的12例),中位PFS为8.1个月,中位OS为20.9个月。BS(34例患者)的总体DCR为30%,中位PFS为2.5个月,中位OS为6.2个月。5例患者(6%)仅在前两个周期内因毒性而停止治疗。另外10例患者在后续治疗周期中因毒性而停止治疗(12%),18例患者(23%)需要调整剂量。45例患者(56%)发生3/4级血液学毒性,有12次发热性中性粒细胞减少发作,1例与治疗相关的死亡。27例患者(3