The time course of neutropenia was well characterized by the model that was developed, which simultaneously accounts for the acute-immediate neutrophilia response induced by CRS and the HIO myelosuppressive effect produced in the bone marrow. This model suggests that higher doses than those evaluated to date could be used in peritoneal carcinomatosis patients without substantially increasing the risk of severe neutropenia.

Abstract. The objective of this study was to characterize the pharmacokinetics and the time course of the neutropenia-induced by hyperthermic intraperitoneal oxaliplatin (HIO) after cytoreductive surgery in cancer patients with peritoneal carcinomatosis. Data from 30 patients who received 360 mg/m 2 of HIO following cytoreductive surgery were used for pharmacokinetic-pharmacodynamic (PK/PD) analysis. The oxaliplatin plasma concentrations were characterized by an open two-compartment pharmacokinetic model after first-order absorption from peritoneum to plasma. An oxaliplatin-sensitive progenitor cell compartment was used to describe the absolute neutrophil counts in blood. The reduction of the proliferation rate of the progenitor cells was modeled by a linear function of the oxaliplatin plasma concentrations. The typical values of oxaliplatin absorption and terminal half-lives were estimated to be 2.2 and 40 h, with moderate interindividual variability. Oxaliplatin reduced the proliferation rate of the progenitor cells by 18.2% per mg/L. No patient's covariates were related to oxaliplatin PK/PD parameters. Bootstrap and visual predictive check evidenced the model was deemed appropriate to describe oxaliplatin pharmacokinetics and the incidence and severity of neutropenia. A peritoneum oxaliplatin exposure of 65 and 120 mg·L/h was associated with a 20% and 33% incidence of neutropenia grade 4. The time course of neutropenia following HIO administration was well described by the semiphysiological PK/PD model. The maximum tolerated peritoneum oxaliplatin exposure is 120 mg L/h and higher exposures should be avoided in future studies. We suggest the prophylactic use of granulocyte colony stimulating factor for patients treated with HIO exposure higher than 65 mg L/h.

BackgroundDiagnosis and treatment of differentiated thyroid carcinomas (DTC) cause anxiety and depression. Additionally, these patients suffer hormonal alterations that are associated with psychological symptoms (e.g., changes in mood, emotional instability, and memory loss). This study aims to evaluate the effectiveness of a psycho-oncological intervention based on counseling to reduce anxiety and depression related to the treatment in patients with DTC.MethodsA non-randomized controlled study, with two groups [experimental group (EG), n = 37, and control group (CG), n = 38] and baseline and posttreatment measures, was designed. Patients in the EG received a psycho-oncological intervention based on counseling in addition to the standard treatment. The independent variable was the assigned group and the dependent one was the evolution of anxiety and depression, which were analyzed separately, and both were evaluated using the Hospital Anxiety and Depression Scale. Other relevant covariables related to the quality of life (QoL) were also analyzed using Short Form-36 Health Survey and Psychological General Wellbeing Index scales.ResultsThe difference of the posttreatment-baseline variation showed a statistically significant reduction in anxiety and depression in the EG in relation to the CG (p < 0.001). The mean of the Psychological General Wellbeing Index scales score increased significantly in the EG (p < 0.001) and decreased significantly in the CG (p < 0.001). All the baseline and the posttreatment scores of the variables evaluated showed a statistically significant improvement in the EG vs. the CG.ConclusionThis study demonstrates significant benefits of psycho-oncological intervention based on counseling in anxiety, depression, QoL, and wellbeing of the patient with differentiated thyroid carcinomas.

This method was successfully applied to the determination of the drug in the plasma of 2 patients with cancer receiving sorafenib 200 and 400 mg orally twice daily, respectively, and could be useful for TDM of sorafenib in routine clinical practice.