Assessment of pharmacokinetic interaction between rilotumumab and epirubicin, cisplatin and capecitabine (ECX) in a Phase 3 study in gastric cancer

Zhang, Yilong; Kuchimanchi, Mita; Zhu, Min; Doshi, Sameer; Hoang, Tien; Kasichayanula, Sreeneeranj

doi:10.1111/bcp.13179

Cited by 6 publications

(4 citation statements)

References 31 publications

(49 reference statements)

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“…Etoposide, a widely used drug for SCLC treatment, has been found to possess repressive impacts on the function of CYP3A4 and CYP2C9 [ 17 ]. In clinical practice, special attention is also given to the potential drug interactions between cisplatin, or anti-PDL1 antibody atezolizumab when they are in combination therapy during cancer treatment [ 18 , 19 ]. Patients with cancers are highly susceptible to DDIs due to the co-administration of anticancer drugs with other medications.…”

Section: Introductionmentioning

confidence: 99%

Metabolism characterization and toxicity of N-hydap, a marine candidate drug for lung cancer therapy by LC–MS method

Lu,

Liang,

et al. 2024

Nat. Prod. Bioprospect.

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N-Hydroxyapiosporamide (N-hydap), a marine product derived from a sponge-associated fungus, has shown promising inhibitory effects on small cell lung cancer (SCLC). However, there is limited understanding of its metabolic pathways and characteristics. This study explored the in vitro metabolic profiles of N-hydap in human recombinant cytochrome P450s (CYPs) and UDP-glucuronosyltransferases (UGTs), as well as human/rat/mice microsomes, and also the pharmacokinetic properties by HPLC–MS/MS. Additionally, the cocktail probe method was used to investigate the potential to create drug-drug interactions (DDIs). N-Hydap was metabolically unstable in various microsomes after 1 h, with about 50% and 70% of it being eliminated by CYPs and UGTs, respectively. UGT1A3 was the main enzyme involved in glucuronidation (over 80%), making glucuronide the primary metabolite. Despite low bioavailability (0.024%), N-hydap exhibited a higher distribution in the lungs (26.26%), accounting for its efficacy against SCLC. Administering N-hydap to mice at normal doses via gavage did not result in significant toxicity. Furthermore, N-hydap was found to affect the catalytic activity of drug metabolic enzymes (DMEs), particularly increasing the activity of UGT1A3, suggesting potential for DDIs. Understanding the metabolic pathways and properties of N-hydap should improve our knowledge of its drug efficacy, toxicity, and potential for DDIs. Graphical Abstract

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Section: Introductionmentioning

confidence: 99%

Metabolism characterization and toxicity of N-hydap, a marine candidate drug for lung cancer therapy by LC–MS method

Lu,

Liang,

et al. 2024

Nat. Prod. Bioprospect.

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“…Accumulated reports suggest that HGF is important for OC progression, and anti-HGF antibodies have been developed as a targeted OC therapeutics. Several HGF-targeting antibodies, such as Rilotumumab, Ficlatuzumab, and HuL2G have been tested in clinical trials, but they were discontinued because no therapeutic effects were observed in patients with gastric cancer, pulmonary adenocarcinoma, or non-small cell lung cancer (22)(23)(24)(25). Unlike these three antibodies that bind to the HGF β-chain, YYB-101 effectively blocks c-MET signaling by binding to the HGF α-chain involved in the high-affinity binding of c-MET .…”

Section: Discussionmentioning

confidence: 99%

YYB-101, a Humanized Antihepatocyte Growth Factor Monoclonal Antibody, Inhibits Ovarian Cancer Cell Motility and Proliferation

Kim

Heo

2021

Anticancer Res

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Background/Aim: Hepatocyte growth factor (HGF) acts as a key regulator in promoting ovarian cancer metastasis. Previously, we observed that YYB-101, a humanized anti-HGF antibody, effectively inhibits ovarian cancer cell migration, invasion, and progression. Here, we evaluated the signaling mechanisms affected by YYB-101 that are important in ovarian cancer cell progression. Materials and Methods: Using cell migration, invasion and proliferation assays, we evaluated the effects of YYB-101 on A2780/luc and SKOV3 cells. The effects of YYB-101 on signaling molecules were determined by immunocytochemistry and immunoblot analysis. Results: YYB-101 inhibited HGF-induced ovarian cancer cell motility by down-regulating paxillin phosphorylation and actincytoskeleton rearrangement. Also, YYB-101 inhibited ovarian cancer cell proliferation by reducing c-MET phosphorylation and activating apoptosis in vitro and in vivo. These effects were significantly enhanced by combining YYB-101 treatment with paclitaxel, a standard chemotherapy drug. Conclusion: YYB-101 can be examined as a new therapeutic agent for the treatment of patients with ovarian cancer.

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“…The PPCs of drugs used in this study are listed as follows: adriamycin, 0.5 µg/mL; cisplatin, 2.4 µg/mL; gemcitabine, 5 µg/mL; oxaliplatin, 3 µg/mL; 5-fluorouracil, 27 µg/mL. 17–21 Each assay was repeated in triplicate.…”

Section: Methodsmentioning

confidence: 99%

High-throughput three-dimensional spheroid tumor model using a novel stamp-like tool

Liao

Wang

et al. 2019

J Tissue Eng

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Spheroid culture is a widely used three-dimensional culture technology that simulates the three-dimensional structure of tumors in vivo and has been considered a good model for tumor research. However, current commercialized spheroid culture tools have the shortcomings of high cost or relatively poor spheroid-forming results for some special cells. To solve such problems, we designed a 3D printed, reusable, stamp-like resin mold that could shape microstructures for spheroid culture of tumor cells on the surface of agarose substrate in a 96-well plate. We applied this homemade three-dimensional culture tool in spheroid formation for hepatocellular carcinoma cells. The experimental data show that the effect of spheroid culture on four hepatocellular carcinoma cell lines in our homemade spheroid culture plate is better than that of the commercialized ultralow attachment spheroid culture plate, and compared to two-dimensional culture, three-dimensional culture improves cell functions. In addition, the drug-sensitive test based on patient-derived hepatocellular carcinoma cells showed a different pattern between spheroid and two-dimensional cultures. In conclusion, our spheroid culture tool is characterized by its low cost, reusability, low cell consumption, convenience in medium exchange, and good effect of spheroid formation, suggesting that this technique could be widely used in individual treatment and high-throughput drug screening.

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Assessment of pharmacokinetic interaction between rilotumumab and epirubicin, cisplatin and capecitabine (ECX) in a Phase 3 study in gastric cancer

Abstract: The results suggest lack of PK-based DDI between rilotumumab and ECX.

Cited by 6 publications

References 31 publications

Metabolism characterization and toxicity of N-hydap, a marine candidate drug for lung cancer therapy by LC–MS method

Metabolism characterization and toxicity of N-hydap, a marine candidate drug for lung cancer therapy by LC–MS method

YYB-101, a Humanized Antihepatocyte Growth Factor Monoclonal Antibody, Inhibits Ovarian Cancer Cell Motility and Proliferation

High-throughput three-dimensional spheroid tumor model using a novel stamp-like tool

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