Pharmacokinetics and safety of cyclophosphamide and docetaxel in a hemodialysis patient with early stage breast cancer: a case report

Abstract

BackgroundStandardized chemotherapy used in cancer patients with severe kidney insufficiency is ineffective. Although there are some pharmacokinetic studies on cyclophosphamide in kidney insufficiency patients, to the best of our knowledge, the pharmacokinetics and safety of combination of cyclophosphamide and docetaxel as postoperative chemotherapy in a patient with early stage breast cancer undergoing hemodialysis is unclear thus far.Case PresentationThe patient received regular TC regimen (cyclophosphamide 600 mg/m2, docetaxel 75 mg/m2). She underwent hemodialysis 48 h after chemotherapy. Blood samples at multiple time-points were collected for determination of plasma levels of cyclophosphamide and docetaxel. Pharmacokinetic analyses indicated that compared with the reference data, the in vivo half-life (66.96 h) and drug exposure (150 %) of cyclophosphamide significantly increased; however, pharmacokinetic parameters of docetaxel was unaffected. Patient developed grade I thrombocytopenia and grade III leukopenia without any other severe adverse reactions. In total, four cycles of treatment were completed. After the chemotherapy, the patient received tamoxifen as endocrine therapy for one and a half years. No recurrence was reported.ConclusionThese results suggest that the standard TC regimen is mostly safe and could be used as postoperative adjuvant chemotherapy for hemodialysis patients with early stage breast cancer.

Predicting Metabolism‐Related Drug–Drug Interactions Using a Microphysiological Multitissue System

“…Due to the negative impact of higher concentrations of KCZ on hLiMT health ( Figure S2, Supporting Information), we selected RTV as the CYP3A4 inhibitor for all DDI experiments. Based on previous experiments we used CP and IFF concentrations of 1 × 10 −3 m. [33] Maximum blood plasma concentrations in patients, depending on the administration route and dosing regimen, were reported to range between 80 × 10 −6 and 157 × 10 −6 m for CP [50][51][52] and between 75 × 10 −6 and 350 × 10 −6 m for IFF. [53][54][55] RTV successfully inhibited CYP3A4 at concentrations of 1 × 10 −6 m, while reported blood plasma concentrations in HIV patients were between 10 × 10 −6 and 22 × 10 −6 m. [56] Compared to the in vivo situation, our testing system required tenfold higher prodrug concentrations but a comparably low RTV concentration to obtain full CYP3A4 inhibition.…”

Decreased Disposition of Anticancer Drugs Predominantly Eliminated via the Liver in Patients with Renal Failure

“…The AUC in the hemodialysis group only increased by 23%, suggesting the removal of cyclophosphamide into the dialysate. A patient who underwent hemodialysis treated with cyclophosphamide 600 mg/m 2 and docetaxel 75 mg/m 2 (TC regimen) displayed a 50% increase in drug exposure [70]. In another report, the elimination of cyclophosphamide in a patient with moderate renal insufficiency was also reduced when compared to a reference population, resulting in a 67% increased exposure to this compound [71].…”

“…The occurrence and severity of adverse events associated with docetaxel were also not increased owing to the reduced renal function. Docetaxel AUC was unaffected in a patient who underwent hemodialysis and received regular TC regimen [70]. Furthermore, in a preliminary study including 11 patients with advanced urothelial carcinoma and renal impairment [73], the treatment with 100 mg/m 2 docetaxel was relatively well-tolerated with no treatment-related deaths; an evident relationship between renal function and toxicity did not exist.…”

Evaluating patient-specific neoadjuvant regimens for breast cancer via a mathematical model constrained by quantitative magnetic resonance imaging data

“…Here we expand the model (from [25] ) to acknowledge their differing efficacies and decay rates using the following equation: where is the efficacy of each drug, is the initial concentration of each drug for each dose with being time relative to the patient scan data (described in more detail below), and the exponential decay terms ( ) represent the eventual washout of the drug over time after each dose. The and parameters are calibrated for each patient and each drug, where the calibration is restricted using bounds defined from ranges in the literature for the terminal elimination half-lives of each drug [39] , [40] , [41] , [42] , [43] , [44] . The initial concentration of drug, , is approximated using the DCE-MRI data as described above in Section 2.3 (see Supplemental materials).…”