Paclitaxel and Carboplatin in Combination with Low-intensity Pulsed Ultrasound for Glioblastoma.

Autor:	Habashy KJ; Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.; Northwestern Medicine Lou and Jean Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois., Dmello C; Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.; Northwestern Medicine Lou and Jean Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois., Chen L; Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.; Northwestern Medicine Lou and Jean Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois., Arrieta VA; Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.; Northwestern Medicine Lou and Jean Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois., Kim KS; Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.; Northwestern Medicine Lou and Jean Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois., Gould A; Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.; Northwestern Medicine Lou and Jean Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois., Youngblood MW; Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.; Northwestern Medicine Lou and Jean Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois., Bouchoux G; Carthera, Lyon, France., Burdett KB; Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois., Zhang H; Northwestern Medicine Lou and Jean Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.; Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois., Canney M; Carthera, Lyon, France., Stupp R; Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.; Northwestern Medicine Lou and Jean Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.; Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.; Division of Hematology/Oncology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois., Sonabend AM; Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.; Northwestern Medicine Lou and Jean Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2024 Apr 15; Vol. 30 (8), pp. 1619-1629.
DOI:	10.1158/1078-0432.CCR-23-2367
Abstrakt:	Purpose: We recently reported on clinical trials for patients with recurrent glioblastoma where low-intensity pulsed ultrasound and microbubbles (LIPU/MB) improved paclitaxel or carboplatin delivery into the brain. Here, we report variable local tumor control with paclitaxel at the maximal/target dose in our phase I trial (NCT04528680). To address this, we investigated the combination of paclitaxel with carboplatin in preclinical glioma models. Experimental Design: We performed MRI-based analysis to evaluate disease control in patients from our trial. We studied the cytotoxicity of paclitaxel and carboplatin against 11 human glioma lines as monotherapy and in combination at concentrations derived from human intraoperative studies. Synergy was assessed with the Loewe model and the survival benefit evaluated in two xenografts. We examined the effects on cell cycle progression, DNA damage, and apoptosis. Results: Patients treated with paclitaxel and LIPU/MB exhibited variable local tumor control, which correlated with overall survival. We observed limited cross-resistance to paclitaxel and carboplatin in glioma lines, with almost a third of them being exclusively susceptible to one drug. This combination led to susceptibility of 81% of lines and synergy in 55% of them. The combination proved more efficacious in two intracranial xenografts when administered with LIPU/MB, leading to complementary effects on cell cycle arrest. Conclusions: Combining paclitaxel and carboplatin in gliomas may be more efficacious than monotherapy, as in other cancers, due to synergy and independent susceptibility to each drug. These results form the basis for an ongoing phase II trial (NCT04528680) where we investigate this combination with LIPU/MB. (©2024 American Association for Cancer Research.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu