Improvement of Paclitaxel-Associated Adverse Reactions (ADRs) via the Use of Nano-Based Drug Delivery Systems: A Systematic Review and Network Meta-Analysis

Abstract

Pi-Ling Chou, 1, 2,* Ya-Ping Huang, 3, 4,* Meng-Hsuan Cheng, 5–7 Kun-Ming Rau, 8, 9 Yi-Ping Fang 2, 3, 10  1School of Nursing, College of Nursing, Kaohsiung Medical University, Kaohsiung, Taiwan; 2Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 3School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; 4Department of Pharmacy, Antai Tian-Sheng Memorial Hospital, Pingtung, Taiwan; 5Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 6School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 7Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 8Department of Hematology-Oncology, E-Da Cancer Hospital, Kaohsiung, Taiwan; 9School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan; 10Regenerative Medical and Cell Therapy Center, Kaohsiung Medical University, Kaohsiung, Taiwan*These authors contributed equally to this workCorrespondence: Yi-Ping Fang 100, Shih-Chuan 1st Road, San Ming District, Kaohsiung, Taiwan 80708 Tel [phone] ext. 2261Fax [phone]Email [email protected]: Paclitaxel is wildly used in chemotherapy, however, the adverse drug reactions (ADRs) occurred frequently. Various novel nano-based paclitaxel delivery systems were developed. The aim performed systemically review and meta-analyses to evaluate the effect adverse drug reactions (ADRs) of paclitaxel and its nano-based delivery systems.Methods: Systematically searched PubMed, Embase, Web of Science, Cochrane, Clinicalkey, Clinicaltrial.com, ASCO and ESMO. Data of adverse effect were analyzed to odds ratio (ORs) with 95% confidence interval (CI). The quality of studies was assessed with CASP Randomised Controlled Trial Checklist. Statistical analysis was used WinBUGS software (version 1.4.3) with the NetMetaXL interface (version 1.6.1).Results: Twenty-one studies, including 7011 patients and 6 paclitaxel formulations fulfilled the inclusion criteria. In all grade hypersensitivity reactions, comparing to SB-P, people with Lip-P had 0.19 times (95% CI= 0.02, 1.3) of chance, with Nab-P had 0.47 times (95% CI= 0.11, 1.40) of chance, with PPX had 0.44 times (95% CI= 0.03, 5.7) of chance for all grade adverse effect. In All grad neutropenia, comparing to Lip-P, people with SB-P had 0.83 times (95% CI= 0.15, 4.81) of chance for all grade adverse effect; comparing to PM-P, people with SB-P had 0.73 times (95% CI= 0.22, 2.42) of chance for all grade adverse effect. In leucopenia, comparing to Nab-P, people with SB-P had 0.66 times (95% CI= 0.50, 0.87) of chance for all grade adverse effect; comparing to PM-P, people with SB-P had 0.64 times (95% CI= 0.32, 1.16) of chance for all grade adverse effect. The rate of incidence in peripheral sensory neuropathy, myalgias and arthralgias tend to no significant differences between different formulations.Conclusion: Nano-based paclitaxel delivery resulted in fewer hypersensitivity reactions than solvent-based delivery. However, the incidence of neutropenia and leucopenia was higher in nano-based than solvent-based paclitaxel delivery. Dose-dependent ADRs were more frequent in paclitaxel anticancer treatment.Keywords: paclitaxel, nano-based paclitaxel delivery systems, adverse reaction, network meta-analysis

Keywords

• paclitaxel
• nano-based paclitaxel delivery systems
• adverse reaction
• network meta-analysis