Image Guidance Volume-Modulated Arc Radiation Therapy Concurrently With Nab-Paclitaxel Plus Cisplatin for Patients With Locally Advanced Cervical Cancer: A Single-Arm Dose Escalation Trial

Purpose: Nanoparticle albumin-bound (nab) paclitaxel has improved uptake by tumor cells in comparison to paclitaxel. The aim of this study was to determine the maximal tolerated dose (MTD) and the dose-limiting toxicity (DLT) of nab-paclitaxel plus cisplatin with concurrent image guidance volume modulated arc therapy for locally advanced cervical cancer (LACC).Methods and Materials: This single-arm phase 1 trial followed the standard 3 + 3 dose escalation design. Patients with histo-logically proven stage IB2-IVA LACC were eligible. Image guidance volume modulated arc therapy included 50.4 Gy in 28 fractions to the pelvis and 59.4 Gy simultaneous boost in 28 fractions to involved pelvic and para-aortic lymph nodes, and sub-sequent high-dose-rate intracavitary brachytherapy at a total dose of 30.0 Gy in 5 fractions, twice a week. Concurrent chemo-therapy regimen included weekly cisplatin (40 mg/m2) and weekly nab-paclitaxel at escalating doses (10, 20, 33, 50, and 70 mg/m2 per week). Duration of the planned treatment was 8 weeks. Grade 4 hematologic toxicity and grade 3 or above nonhe-matologic toxicity were considered as DLT. MTD was defined as the highest dose with <= 33% DLT.Results: A total of 22 patients were enrolled from September 2019 to August 2021. The most common adverse events were grade 1 to 3 leukopenia, diarrhea, and nausea/vomiting. A total of 4 patients (18.0%) experienced DLT: grade 3 hypokalemia at 33 mg/m2 (1 of 6 subjects), grade 3 deep vein thrombosis at 50 mg/m2 (1 of 6) and 70 mg/m2 (1 of 4), and grade 3 perineum edema at 70 mg/m2 (1 of 3). The estimated MTD was 50 mg/m2. Complete response was observed in 20 patients (90.9%). Conclusions: In patients undergoing concurrent IG-VAMT with nab-paclitaxel plus cisplatin for LACC, MTD of nab-pacli-taxel was 50 mg/m2. Complete response rate was 90.9%. (c) 2022 Published by Elsevier Inc.

Automated summary

The purpose of this study was to determine the maximal tolerated dose (MTD) and dose-limiting toxicity (DLT) of nab-paclitaxel plus cisplatin for locally advanced cervical cancer (LACC) using image guidance volume modulated arc therapy. The study found that the MTD of nab-paclitaxel was 50 mg/m2 and the complete response rate was 90.9%.