Pegylated Liposomal Doxorubicin Combined with Cisplatin for Advanced Osteosarcoma: A Single-dose Dose-escalating Trial
- VernacularTitle:聚乙二醇修饰脂质体阿霉素联合顺铂单次给药治疗晚期骨肉瘤的剂量递增试验
- Author:
Xi-zhi WEN
1
;
Qiu-zhong PAN
1
;
De-sheng WENG
1
;
Jing-jing ZHAO
1
;
Hai-rong XU
2
;
Zhen HUANG
2
;
Xiao-hui NIU
2
;
Xing ZHANG
1
Author Information
1. Melanoma and Sarcoma Medical Oncology Unit, Biotherapy Center, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
2. Department of Orthopaedic Oncology Surgery, Jishuitan Hospital, Beijing 100000, China
- Publication Type:Journal Article
- Keywords:
osteosarcoma;
pegylated liposome doxorubicin(PLD);
phase I clinical trial
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2020;41(4):582-588
- CountryChina
- Language:Chinese
-
Abstract:
【Objective】 To explore the maximum tolerated dose(MTD) of pegylated liposome doxorubicin(PLD) when combined with cisplatin as a modified regimen for osteosarcoma. 【Methods】 A total of 14 patients with pathologically confirmed metastatic or unresectable osteosarcoma received one cycle of PLD combined with cisplatin therapy. The study used a traditional 3+3 design, with three PLD dose levels(40, 50, and 60 mg/ m2, day 1). It was designed to recruit three patients initially at each dose level. Cisplatin was given at a dose of 100 mg/m2(administered within four days) for each patients. Patients received prophylactic granulocyte stimulating factor therapy 48 h after chemotherapy. Toxicities were documented according to the the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0(NCI CTCAE v4.0) . 【Results】 Of the 14 patients, 9 were male and 5 female, with a median age of 20 years(range 14~43). Both of the patients at dose level of 60 mg/m2 experienced dose-limiting toxicity(DLT) (grade 3 oral mucositis and grade 4 neutropenic fever). Only 1 of the 9 patients at dose level of 50 mg/m2 experienced DLT(grade 4 thrombocytopenia lasting for more than 3 days) and thus the MTD was 50 mg/m2. Most common grade 3~4 adverse events across all cohorts included neutropenia(12 cases, 12/14), thrombocytopenia(7 cases, 7/14), anemia(4 cases, 4/14) and oral mucositis(2 cases, 2/14). All the adverse events were relieved after symptomatic and supportive treatment. No treatment-related death was observed. 【Conclusions】 For advanced osteosarcoma, when combined with cisplatin, the MTD of PLD was 50 mg/m2. The main DLT was oral mucositis and neutropenic fever. The adverse events can be relieved after symptomatic treatment.
