{"title":"洛铂联合图像引导体积调制弧线放射治疗局部晚期宫颈癌的 I 期临床试验","authors":"","doi":"10.1016/j.ijrobp.2024.07.012","DOIUrl":null,"url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>We aimed to determine the maximum tolerable dose (MTD) and dose-limiting toxicity (DLT) of weekly lobaplatin combined with concurrent radiotherapy using image-guided volumetric modulated arc therapy (VMAT) and brachytherapy in locally advanced cervical cancer (LACC) patients.</div></div><div><h3>Materials/Methods</h3><div>Patients with clinical stage IB3-IVA cervical cancer were enrolled and received image-guided volume-modulated arc radiation therapy and brachytherapy combined with concurrent weekly lobaplatin following a standard 3+3 dose escalation design. Patients received 45 Gy in 25 fractions to the pelvis and 60 Gy in 25 fractions to the involved pelvic and para-aortic lymph nodes. High-dose-rate intracavitary brachytherapy was conducted weekly during the fourth or fifth week of radiation at a dose of 28 Gy in 4 fractions. The starting weekly dose of lobaplatin 8 mg/m<sup>2</sup>, which was subsequently successively increased by 2 mg/m<sup>2</sup> for a total of 5 levels. The primary endpoints were the MTD and DLT of weekly lobaplatin. DLTs were defined as follows: (1) grade 4 hematologic toxicity, febrile neutropenia, or grade 3 or higher thrombocytopenia with bleeding; (2) grade 3 or higher nonhematologic toxicity (except nausea, vomiting, or alopecia); and (3) less than 3 cycles of lobaplatin due to treatment-related toxicity.</div></div><div><h3>Results</h3><div>Between December 30 and October 19, there were 21 patients who were enrolled in this study. All patients completed image-guided volume-modulated arc radiotherapy and brachytherapy per protocol. Three patients experienced DLTs: grade 3 fatigue at 14 mg/m<sup>2</sup>, two cycles of chemotherapy at 16 mg/m<sup>2</sup>, and grade 3 fatigue at 16 mg/m<sup>2</sup>. Grade 3 hematologic toxicities were observed only at 14 mg/m<sup>2</sup> and 16 mg/m<sup>2</sup>, with 7 patients (33.3%) having leukopenia and 1 (4.8%) having neutropenia. The only severe and dose-limiting nonhematologic toxicity was Grade 3 fatigue. The MTD of weekly lobaplatin was 14 mg/m<sup>2</sup>.</div></div><div><h3>Conclusion</h3><div>In this phase I clinical trial, the MTD of weekly lobaplatin combined with image-guided volume-modulated arc radiation therapy and brachytherapy for LACC was found to be 14 mg/m<sup>2</sup>.</div></div>","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":null,"pages":null},"PeriodicalIF":6.4000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Phase I Clinical Trial of Lobaplatin Combined with Image-Guided Volume-Modulated Arc Radiation Therapy in Locally Advanced Cervical Cancer\",\"authors\":\"\",\"doi\":\"10.1016/j.ijrobp.2024.07.012\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Purpose/Objective(s)</h3><div>We aimed to determine the maximum tolerable dose (MTD) and dose-limiting toxicity (DLT) of weekly lobaplatin combined with concurrent radiotherapy using image-guided volumetric modulated arc therapy (VMAT) and brachytherapy in locally advanced cervical cancer (LACC) patients.</div></div><div><h3>Materials/Methods</h3><div>Patients with clinical stage IB3-IVA cervical cancer were enrolled and received image-guided volume-modulated arc radiation therapy and brachytherapy combined with concurrent weekly lobaplatin following a standard 3+3 dose escalation design. Patients received 45 Gy in 25 fractions to the pelvis and 60 Gy in 25 fractions to the involved pelvic and para-aortic lymph nodes. High-dose-rate intracavitary brachytherapy was conducted weekly during the fourth or fifth week of radiation at a dose of 28 Gy in 4 fractions. The starting weekly dose of lobaplatin 8 mg/m<sup>2</sup>, which was subsequently successively increased by 2 mg/m<sup>2</sup> for a total of 5 levels. The primary endpoints were the MTD and DLT of weekly lobaplatin. DLTs were defined as follows: (1) grade 4 hematologic toxicity, febrile neutropenia, or grade 3 or higher thrombocytopenia with bleeding; (2) grade 3 or higher nonhematologic toxicity (except nausea, vomiting, or alopecia); and (3) less than 3 cycles of lobaplatin due to treatment-related toxicity.</div></div><div><h3>Results</h3><div>Between December 30 and October 19, there were 21 patients who were enrolled in this study. All patients completed image-guided volume-modulated arc radiotherapy and brachytherapy per protocol. Three patients experienced DLTs: grade 3 fatigue at 14 mg/m<sup>2</sup>, two cycles of chemotherapy at 16 mg/m<sup>2</sup>, and grade 3 fatigue at 16 mg/m<sup>2</sup>. Grade 3 hematologic toxicities were observed only at 14 mg/m<sup>2</sup> and 16 mg/m<sup>2</sup>, with 7 patients (33.3%) having leukopenia and 1 (4.8%) having neutropenia. The only severe and dose-limiting nonhematologic toxicity was Grade 3 fatigue. The MTD of weekly lobaplatin was 14 mg/m<sup>2</sup>.</div></div><div><h3>Conclusion</h3><div>In this phase I clinical trial, the MTD of weekly lobaplatin combined with image-guided volume-modulated arc radiation therapy and brachytherapy for LACC was found to be 14 mg/m<sup>2</sup>.</div></div>\",\"PeriodicalId\":14215,\"journal\":{\"name\":\"International Journal of Radiation Oncology Biology Physics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":6.4000,\"publicationDate\":\"2024-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Radiation Oncology Biology Physics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0360301624007740\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Radiation Oncology Biology Physics","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0360301624007740","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
Phase I Clinical Trial of Lobaplatin Combined with Image-Guided Volume-Modulated Arc Radiation Therapy in Locally Advanced Cervical Cancer
Purpose/Objective(s)
We aimed to determine the maximum tolerable dose (MTD) and dose-limiting toxicity (DLT) of weekly lobaplatin combined with concurrent radiotherapy using image-guided volumetric modulated arc therapy (VMAT) and brachytherapy in locally advanced cervical cancer (LACC) patients.
Materials/Methods
Patients with clinical stage IB3-IVA cervical cancer were enrolled and received image-guided volume-modulated arc radiation therapy and brachytherapy combined with concurrent weekly lobaplatin following a standard 3+3 dose escalation design. Patients received 45 Gy in 25 fractions to the pelvis and 60 Gy in 25 fractions to the involved pelvic and para-aortic lymph nodes. High-dose-rate intracavitary brachytherapy was conducted weekly during the fourth or fifth week of radiation at a dose of 28 Gy in 4 fractions. The starting weekly dose of lobaplatin 8 mg/m2, which was subsequently successively increased by 2 mg/m2 for a total of 5 levels. The primary endpoints were the MTD and DLT of weekly lobaplatin. DLTs were defined as follows: (1) grade 4 hematologic toxicity, febrile neutropenia, or grade 3 or higher thrombocytopenia with bleeding; (2) grade 3 or higher nonhematologic toxicity (except nausea, vomiting, or alopecia); and (3) less than 3 cycles of lobaplatin due to treatment-related toxicity.
Results
Between December 30 and October 19, there were 21 patients who were enrolled in this study. All patients completed image-guided volume-modulated arc radiotherapy and brachytherapy per protocol. Three patients experienced DLTs: grade 3 fatigue at 14 mg/m2, two cycles of chemotherapy at 16 mg/m2, and grade 3 fatigue at 16 mg/m2. Grade 3 hematologic toxicities were observed only at 14 mg/m2 and 16 mg/m2, with 7 patients (33.3%) having leukopenia and 1 (4.8%) having neutropenia. The only severe and dose-limiting nonhematologic toxicity was Grade 3 fatigue. The MTD of weekly lobaplatin was 14 mg/m2.
Conclusion
In this phase I clinical trial, the MTD of weekly lobaplatin combined with image-guided volume-modulated arc radiation therapy and brachytherapy for LACC was found to be 14 mg/m2.
期刊介绍:
International Journal of Radiation Oncology • Biology • Physics (IJROBP), known in the field as the Red Journal, publishes original laboratory and clinical investigations related to radiation oncology, radiation biology, medical physics, and both education and health policy as it relates to the field.
This journal has a particular interest in original contributions of the following types: prospective clinical trials, outcomes research, and large database interrogation. In addition, it seeks reports of high-impact innovations in single or combined modality treatment, tumor sensitization, normal tissue protection (including both precision avoidance and pharmacologic means), brachytherapy, particle irradiation, and cancer imaging. Technical advances related to dosimetry and conformal radiation treatment planning are of interest, as are basic science studies investigating tumor physiology and the molecular biology underlying cancer and normal tissue radiation response.