ABSTRACT
INTRODUCTION: Albumin-bound paclitaxel (nab-PTX), a novel paclitaxel preparation, has been found to successfully blocks tumor progression in breast and lung cancer. However, at the same time of as clinical application, neurotoxicity caused by nab-PTX has become the main factor limiting the clinical application of nab-PTX, which seriously affects the quality of life of patients and increases their psychological or financial burden. In clinical applications, JHGWD combined with bloodletting therapy at the end of the extremities has a positive effect on neurotoxic symptoms such as numbness, pain, and weakness of the hands and feet caused by nab-PTX. In a single-arm experiment, it was also found that the immediate effective rate of exsanguination therapy was as high as 70%, and when combined with oral Chinese medicine treatment, it further improved the efficacy. Therefore, a randomized controlled trial (RCT) was designed to further evaluate the efficacy and safety of this treatment. METHODS: This RCT will be conducted at the Shanxi Provincial Hospital of Traditional Chinese Medicine. A total of 120 patients with Nab-PTX chemotherapy-induced neurotoxicity will be recruited. Treatment groups will be categorized into herbs alone group, bloodletting treatment alone group, and herbs combined with bloodletting group. Blank control was used. The primary outcome will be the EORTC QLQ-CIPN20 scale of the included patients, and the secondary outcomes will include EMG, peripheral neurotoxicity symptom score, NCI-CTCAE5.0 peripheral neurotoxicity grade, and WHO anti-tumor drug peripheral neurotoxicity grade. Adverse reactions will be recorded throughout the process. All data in this RCT will be analyzed by SPSS 26.0 software. DISCUSSION: The results of this RCT will contribute to treating PIPN, relieving the neurotoxic symptoms, and improving the quality of life of patients. Finally, the RCT results will be published in a relevant academic journal on completion of the trial. TRIAL REGISTRATION: ChiCTR2200060217(May22,2022).
Subject(s)
Albumin-Bound Paclitaxel , Lung Neoplasms , Humans , Albumin-Bound Paclitaxel/toxicity , Lung Neoplasms/drug therapy , Randomized Controlled Trials as TopicABSTRACT
To investigate the utility of noninvasive µPET-CT with 64Cu-DOTA-anti-CD11b (64Cu-αCD11b) in assessing bone marrow status after anticancer therapies, and the protective role of anti-CSF-1 (αCSF-1) against bone marrow suppression induced by Abraxane. Methods: MDA-MB-435 tumor-bearing mice were treated with Abraxane, αCSF-1, or αCSF-1 plus Abraxane. µPET-CT and biodistribution of 64Cu-αCD11b were performed after intravenous injection of the radiotracer. Cells from mouse bone marrow and MDA-MB-435 tumor were analyzed by flow cytometry. A humanized αCSF-1 was investigated for its role in protecting bone marrow cells, using a transgenic mouse model that expresses functional human CSF-1. Results: µPET-CT showed that 64Cu-αCD11b had high uptake in the bone marrow and spleen of both normal and tumor-bearing mice. Abraxane significantly reduced 64Cu-αCD11b uptake in the bone marrow and spleen of treated mice compared to untreated mice. Interestingly, 64Cu-αCD11b µPET-CT revealed that αCSF-1 alleviated the depletion of bone marrow cells by Abraxane. These changes in the bone marrow population of CD11b+ myeloid cells were confirmed by flow cytometry. Moreover, αCSF-1 potently enhanced tolerance of bone marrow granulocytic myeloid cells to Abraxane, decreased cell migration, and suppressed recruitment of myeloid cells to the tumor microenvironment. The humanized αCSF-1 also alleviated the effects of Abraxane on bone marrow cells in transgenic mice expressing human CSF-1, suggesting clinical relevance of αCSF-1 in prevention of bone marrow suppression in addition to its role in reducing tumor-infiltrating myeloid cells. Conclusions: Abraxane-induced bone marrow CD11b+ myeloid cell depletion in tumor-bearing mice could be noninvasively assessed by µPET-CT with 64Cu-αCD11b and prevented by αCSF-1.
