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Article
Investigating the influence of relevant pharmacogenetic variants on the pharmacokinetics and pharmacodynamics of orally administered docetaxel combined with ritonavir
The anticancer drug docetaxel exhibits large interpatient pharmacokinetic and pharmacodynamic variability. In this study, we aimed to assess the functional significance of 14 polymorphisms in the CYP3A, CYP1B1...
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Article
Open AccessEffect of Food on the Pharmacokinetics of the Oral Docetaxel Tablet Formulation ModraDoc006 Combined with Ritonavir (ModraDoc006/r) in Patients with Advanced Solid Tumours
ModraDoc006 is a novel docetaxel tablet formulation that is co-administrated with the cytochrome P450 3A4 and P-glycoprotein inhibitor ritonavir (r): ModraDoc006/r.
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Article
Population Pharmacokinetics of Intracellular 5-Fluorouridine 5′-Triphosphate and its Relationship with Hand-and-Foot Syndrome in Patients Treated with Capecitabine
Capecitabine is an oral pro-drug of 5-fluorouracil. Patients with solid tumours who are treated with capecitabine may develop hand-and-foot syndrome (HFS) as side effect. This might be a result of accumulation...
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Article
Quantification of the pharmacokinetic-toxicodynamic relationship of oral docetaxel co-administered with ritonavir
Introduction Oral formulations of docetaxel have successfully been developed as an alternative for intravenous administration. Co-administration with the enzyme inhibitor ritonavir boosts the docetaxel plasma exp...
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Article
Phase I study of continuous olaparib capsule dosing in combination with carboplatin and/or paclitaxel (Part 1)
Background The PARP inhibitor olaparib has shown acceptable toxicity at doses of up to 400 mg twice daily (bid; capsule formulation) with encouraging signs of antitumor activity. Based on its mode of action, olap...
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Article
Phase I study of intermittent olaparib capsule or tablet dosing in combination with carboplatin and paclitaxel (part 2)
Background In the first part of this extensive phase I study (NCT00516724), continuous olaparib twice daily (bid) with carboplatin and/or paclitaxel resulted in myelosuppression and dose modifications. Here, we r...
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Article
Open AccessPhase I pharmacological study of continuous chronomodulated capecitabine treatment
Capecitabine is an oral pre-pro-drug of the anti-cancer drug 5-fluorouracil (5-FU). The biological activity of the 5-FU degrading enzyme, dihydropyrimidine dehydrogenase (DPD), and the target enzyme thymidylat...
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Article
Phase I study of lapatinib plus trametinib in patients with KRAS-mutant colorectal, non-small cell lung, and pancreatic cancer
KRAS oncogene mutations cause sustained signaling through the MAPK pathway. Concurrent inhibition of MEK, EGFR, and HER2 resulted in complete inhibition of tumor growth in KRAS-mutant (KRASm) and PIK3CA wild-type...
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Article
Open AccessPhase 1 study of the pan-HER inhibitor dacomitinib plus the MEK1/2 inhibitor PD-0325901 in patients with KRAS-mutation-positive colorectal, non-small-cell lung and pancreatic cancer
Mutations in KRAS result in a constitutively activated MAPK pathway. In KRAS-mutant tumours existing treatment options, e.g. MEK inhibition, have limited efficacy due to resistance through feedback activation of ...
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Article
Open AccessA phase I followed by a randomized phase II trial of two cycles carboplatin-olaparib followed by olaparib monotherapy versus capecitabine in BRCA1- or BRCA2-mutated HER2-negative advanced breast cancer as first line treatment (REVIVAL): study protocol for a randomized controlled trial
Preclinical studies in breast cancer models showed that BRCA1 or BRCA2 deficient cell lines, when compared to BRCA proficient cell lines, are extremely sensitive to PARP1 inhibition. When combining the PARP1 inhi...
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Article
A phase 0 clinical trial of novel candidate extended-release formulations of capecitabine
To examine the pharmacokinetic (PK) profile of several candidate extended-release (ER) formulations of capecitabine in patients.
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Article
Open AccessLong-term safety and anti-tumour activity of olaparib monotherapy after combination with carboplatin and paclitaxel in patients with advanced breast, ovarian or fallopian tube cancer
Olaparib (AZD2281), a PARP-1/2 inhibitor, has been extensively investigated in clinical trials. However, limited clinical data are available about its long-term safety and anti-tumour activity.
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Article
“Effect of the drug transporters ABCB1, ABCC2, and ABCG2 on the disposition and brain accumulation of the taxane analog BMS-275,183”
BMS-275,183 is a novel oral C-4 methyl carbonate analogue of paclitaxel. Recently, a drug-drug interaction between BMS-275,183 and benzimidazole proton pump inhibitors (PPIs) was suggested in clinical trials r...
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Article
The Effect of St John’s Wort on the Pharmacokinetics of Docetaxel
St John’s wort (SJW), a herbal antidepressant, is commonly used by cancer patients, and its component hyperforin is a known inducer of the cytochrome P450 (CYP) isoenzyme 3A4. Here, the potential pharmacokinet...
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Article
Effect of the drug transporters ABCG2, Abcg2, ABCB1 and ABCC2 on the disposition, brain accumulation and myelotoxicity of the aurora kinase B inhibitor barasertib and its more active form barasertib-hydroxy-QPA
We explored whether barasertib (AZD1152), a selective Aurora B kinase inhibitor, is a substrate for P-glycoprotein (Pgp, MDR1), breast cancer resistance protein (BCRP), and multidrug resistance protein 2 (MRP2...
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Article
Erratum to: Effect of the drug transporters ABCG2, Abcg2, ABCB1 and ABCC2 on the disposition, brain accumulation and myelotoxicity of the aurora kinase B inhibitor barasertib and its more active form barasertib-hydroxy-QPA
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Article
Pharmacokinetic evaluation of three oral formulations of docetaxel boosted with ritonavir: two single-drug formulations vs. a fixed-dose combination tablet
The ability to deliver the potent anti-cancer agent docetaxel via the oral route may enable the development of promising new treatment regimens with reduced toxicity, increased efficacy, and increased patient ...
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Article
Disposition and metabolism of 14C-dovitinib (TKI258), an inhibitor of FGFR and VEGFR, after oral administration in patients with advanced solid tumors
This study investigated the metabolism and excretion of dovitinib (TKI258), a tyrosine kinase inhibitor that inhibits fibroblast, vascular endothelial, and platelet-derived growth factor receptors, in patients...
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Article
The effect of hydroxyurea on P-glycoprotein/BCRP-mediated transport and CYP3A metabolism of imatinib mesylate
It has been reported that the combination therapy of imatinib mesylate, a tyrosine kinase inhibitor, plus hydroxyurea, a ribonucleotide reductase inhibitor, is associated with remarkable antitumor activity in ...
