Phase I Clinical Trial of Lobaplatin Combined with Image-Guided Volume-Modulated Arc Radiation Therapy in Locally Advanced Cervical Cancer

Abstract

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.