Efficacy and safety evaluation of albumin-bound paclitaxel chemotherapy in East Asian patients with gynecological tumors based on the degree of paclitaxel binding to patient plasma.

Nab-PTX is a special dosage form of antitumor drug that is different from other injections. In order to explore the efficacy and safety of albumin-bound paclitaxel, we developed an analytical method with UPLC-MS/MS to quantify the total and free paclitaxel in plasma, and prospectively evaluate the impact of unbound fraction fu (%) on the prognosis and adverse reactions of patients with gynecological tumors. From 2020.10 to 2021.10, a total of 116 patients with gynecological tumors were included, application of albumin-bound paclitaxel combined with platinum chemotherapy drugs, the blood collection time is 18-30 h after nab-PTX intravenous infusion. The collection time and the start (end) time of intravenous drip are recorded correctly, and a high-precision and sensitive UPLC-MS/MS method for the simultaneous determination of total and free paclitaxel was established. With fu (%) = Cunbound/Ctotal as the evaluation index, the concentration of total paclitaxel and free paclitaxel were determined by UPLC-MS/MS. The value of fu (%) was closely related to clinical adverse reactions, neutropenia, thrombocytopenia, leukopenia and bone marrow suppression. Neurotoxicity was statistically remarkable ( P up0.001), and fu (%) has a significant correlation with clinical efficacy ( P up0.001). We have developed a highly precise, highly sensitive and specific UPLC-MS/MS method for the simultaneous determination of binding and free albumin-bound paclitaxel concentrations in patients' serum. In addition, we found that fu (%) could be used as the detection index. The higher the fu (%) was, the more taxol could be free, the more adverse reactions related to toxic events occurred in patients.

Effect of concomitant antibiotics use on patient outcomes and adverse effects in patients treated with ICIs.

Background: Immune checkpoint inhibitors (ICIs) such as PD-1/PD-L1/CTLA-4 inhibitors have brought new opportunities for the cure of cancer patients and have been widely used and which are the most successful cancer immunotherapy drug in recent years. Gut microbiome and metabolites exert a critical regulatory function in cancer immunotherapy of ICIs, which can be affected by antibiotics intervention. However, inflammatory infections caused by impaired immune function in tumor patients often require antibiotic treatment.Objective: In this review, we briefly discussed the correlation between antibiotics and ICIs treatment to evaluate the impact of antibiotics on cancer progression.Methods: By searches of PubMed, we collected the data such as progression-free survival time (PFS) and overall survival time (OS) in patients with non-small cell lung cancer (NSCLC), kidney cancer, Melanoma, colorectal cancer, and other tumors.Results: Antibiotics have a negative effect on the prolongation of survival in cancer patients treated with ICIs. This may depend on the patient's cancer type and the type of ICIs and antibiotics they have used.Conclusions: Antibiotics may reduce the effectiveness of immunotherapy by depleting the body's microbiome. Therefore, paying attention to the changes in the level of microorganisms in cancer patients, while making more individualized and precise improvements in treatment regimens, may bring new opportunities to improve the efficacy of immunotherapy.

Correlation between pharmacokinetic parameters of 5-fluorouracil and related metabolites and adverse reactions in East-Asian patients with advanced colorectal cancer.

BACKGROUND AND OBJECTIVE: To examine the range of the area under the concentration-time curve (AUC) calculated using plasma 5-FU concentration at steady-state plasma concentration-time of 5-fluorouracil (5-FU) and correlation between 5-FU metabolites (5,6-dihydro-5-fluorouracil, 5-FUH2 and α-fluoro-ß-Alanine, FBAL) plasma concentration and adverse reactions when patients with advanced colorectal cancer (CRC) received 5-FU-based chemotherapy. METHODS: 74 patients with advanced CRC receiving 5-FU-based chemotherapy from Aug. 2017 to Nov. 2020 in Harbin Medical University Cancer Hospital were involved in this study, the dosage of 5-FU being determined according to the patient's body surface area (BSA). Using an ultra-high performance liquid chromatography-tandem mass spectrum (UPLC-MS/MS) to determine the 5-FU steady-state plasma concentration (CSS) and plasma concentration of 5-FUH2 and FBAL in CRC patients receiving 5-FU in continuous intravenous infusion for 18-30 h, the start time and end time of 5-FU infusion in patients were accurately recorded and the continuous infusion time (TCI) was calculated. The AUC value was calculated according to AUC = CSS × TCI. At the same time, the treatment effects and adverse drug reactions of patients were evaluated, to analyze the relationship between 5-FU AUC, 5-FUH2 and FBAL plasma concentration and clinical efficacy and adverse reactions in CRC patients, and explore the ideal AUC range of 5-FU in the treatment of colorectal cancer. RESULTS: The AUC of 5-FU was not normally distributed and ranged from 3.13 to 41.12mgh/L, with an average value of 14.81 ± 8.62 mg·h /L, and the AUC values had obvious inter-individual differences up to 13 times. 5-FUH2 ranged from 131.98 to 987.93 ng/mL, with an average of 550.58 ± 260.60 ng/mL; FBAL ranged from 23.58 to 262.48 ng/mL, with an average of 89.79 ± 58.47 ng/mL. Correlation analysis results revealed a significant correlation between 5-FU AUC, 5-FUH2 and FABL plasma concentration and adverse reactions, 5-FU AUC and clinical efficacy. CONCLUSIONS: There are obvious individual differences in AUC values in CRC patients receiving different dosages of 5-FU based on BSA. The ideal AUC range of 5-FU is 18.23-29.17 mg·h/L. There was a significant correlation between 5-FUH2 and FABL plasma concentration and adverse reactions.