Image-guidance volume modulated arc radiotherapy concurrently with Nab-paclitaxel plus cisplatin for patients with locally advanced cervical cancer: a single-arm dose escalation trial
Mené en Chine entre 2019 et 2021 sur 22 patientes atteintes d'un cancer du col de l'utérus de stade IB2-IVA (âge médian : 54 ans : durée médiane de suivi : 20 mois), cet essai de phase I évalue la dose maximale tolérée du nab-paclitaxel associé au cisplatine et à une arc thérapie guidée par l'image et avec modulation d'intensité volumétrique
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 (IG-VMAT) for locally advanced cervical cancer (LACC). Patients and Methods: This single-arm phase I trial followed the standard 3 + 3 dose escalation design. Patients with histologically proven stage IB2-IVA LACC were eligible. IG-VMAT 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 subsequent high dose rate intracavitary brachytherapy (HDR-IBT) at a total doses of 30.0 Gy in 5 fractions, twice a week. Concurrent chemotherapy 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 non-hematologic 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 1-3 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-paclitaxel was 50 mg/m2. Complete response rate was 90.9%.
International Journal of Radiation Oncology, Biology, Physics 2022