pm-01183 and Thrombocytopenia

Lurbinectedin is a selective inhibitor of oncogenic transcription. Reversible myelosuppression is its most relevant toxicity. Pharmacokinetic-pharmacodynamic analyses were conducted to characterize the time course of absolute neutrophil count and platelet count recovery and to detect and quantify the effect of relevant covariates in patients with advanced solid tumors treated with lurbinectedin. Absolute neutrophil count, platelet count, and lurbinectedin total plasma concentration were assessed in 244 patients treated with lurbinectedin with varied dosing schedules and doses. A reference extended semimechanistic pharmacokinetic-pharmacodynamic model of myelosuppression was used. Granulocyte colony-stimulating factor (G-CSF) administration was modeled as a dichotomous covariate, and platelet transfusions were included as a bolus dose into the last compartment of the model, representing the central circulation. Final models were suitable to describe the time course of absolute neutrophil count and platelet count recovery. A lurbinectedin dose of 3.2 mg/m

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Carbolines; Dose-Response Relationship, Drug; Female; Granulocyte Colony-Stimulating Factor; Heterocyclic Compounds, 4 or More Rings; Humans; Male; Middle Aged; Models, Biological; Neoplasms; Neutropenia; Neutrophils; Patient Acuity; Platelet Count; Severity of Illness Index; Thrombocytopenia; Young Adult

Lurbinectedin is an alkylating agent approved for the second-line treatment of small cell lung cancer. Although initial studies showed no association between body surface area (BSA) and drug clearance, the recommended dose is 3.2 mg/m

Topics: Anemia; Body Surface Area; Carbolines; Heterocyclic Compounds, 4 or More Rings; Humans; Lung Neoplasms; Thrombocytopenia