ABSTRACT
We report the case of a patient with metastatic breast cancer who presented with an orthostatic headache. After a comprehensive diagnostic workup including MRI and lumbar puncture, we maintained the diagnosis of intracranial hypotension (IH). The patient was therefore treated with two consecutive non targeted epidural blood patches, resulting in the remission of IH symptoms for 6 months. IH in cancer patients is a rarer cause of headache than carcinomatous meningitis. As the diagnosis can be made by standard examination and the treatment is relatively simple and effective, IH deserves to be better known by oncologists.
Subject(s)
Breast Neoplasms , Intracranial Hypotension , Meningeal Carcinomatosis , Humans , Female , Breast Neoplasms/complications , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/therapy , Intracranial Hypotension/complications , Intracranial Hypotension/diagnostic imagingSubject(s)
Breast Neoplasms , Triple Negative Breast Neoplasms , Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Chemotherapy, Adjuvant , Drug Approval , Female , Humans , Neoadjuvant Therapy , Triple Negative Breast Neoplasms/drug therapyABSTRACT
Background: Pazopanib (PAZ) is an oral angiogenesis inhibitor approved to treat soft tissue sarcoma (STS) but associated with a large interpatient pharmacokinetic (PK) variability and narrow therapeutic index. We aimed to define the specific threshold of PAZ trough concentration (Cmin) associated with better progression-free survival (PFS) in STS patients. Methods: In this observational study, PAZ Cmin was monitored over the treatment course. For the primary endpoint, the 3-month PFS in STS was analyzed with logistic regression. Second, we performed exposure−overall survival (OS) (Cox model plus Kaplan−Meier analysis/log-rank test) and exposure−toxicity analyses. Results: Ninety-five STS patients were eligible for pharmacokinetic/pharmacodynamic (PK/PD) assessment. In the multivariable analysis, PAZ Cmin < 27 mg/L was independently associated with a risk of progression at 3 months (odds ratio (OR) 4.21, 95% confidence interval (CI) (1.47−12.12), p = 0.008). A higher average of PAZ Cmin over the first 3 months was associated with a higher risk of grade 3−4 toxicities according to the NCI-CTCAE version 5.0 (OR 1.07 per 1 mg/L increase, CI95 (1.02−1.13), p = 0.007). Conclusion: PAZ Cmin ≥ 27 mg/L was independently associated with improved 3-month PFS in STS patients. Pharmacokinetically-guided dosing could be helpful to optimize the clinical management of STS patients in daily clinical practice.
