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BACKGROUND: Carboplatin is a second-generation platinum agent, commonly used as initial chemotherapy and in second-line or salvage therapy in gynecologic cancers. It is often preferred over cisplatin, because of its relative lack of nephrotoxicity, neurotoxicity, and emetogenicity. As its utilization has increased, cases of hypersensitivity reactions (HSRs) have been documented, with an incidence of approximately 16.8% in patients with ovarian cancer. Patients affected by these reactions must either undergo desensitization or avoid the drug completely, with therapeutic alternatives of unknown comparative efficacy. OBJECTIVE: To compare the overall survival and time to progression (TTP) among patients undergoing carboplatin desensitization after HSR, those receiving a non–platinum-containing regimen after HSR, and patients without HSR who received carboplatin-based therapy. METHODS: This was a single-center, retrospective, case control study between January 1, 2009, and June 30, 2014. Women aged ≥18 years with a confirmed diagnosis of an advanced-stage or recurrent platinum-sensitive gynecologic oncology malignancy, including ovarian, fallopian tube, primary peritoneal, or endometrial cancer, were eligible for study inclusion. Patients were placed into 3 groups: patients undergoing carboplatin desensitization after HSR (Group A); those receiving a non–platinum-containing regimen after HSR (Group B); and those without HSR who were receiving carboplatin-based therapy (Group C). The overall survival and TTP outcomes were assessed for each group. RESULTS: A total of 60 patients were identified for study inclusion, including 15 patients who successfully completed 55 carboplatin cycle desensitizations. The median TTP for Group A, Group B, and Group C was 26.4 months, 20 months, and 18.1 months, respectively (P = .42). Group A had a median overall survival of 48.5 months and Group B had a median overall survival of 50.1 months (P = .16). The median overall survival was not reached in Group C. Overall, 11 (73%) patients in Group A tolerated the carboplatin desensitization without a reaction. CONCLUSION: Carboplatin desensitization in patients with gynecologic cancers did not result in a significantly different median TTP or overall survival compared with patients who continued carboplatin therapy without any HSRs or those who switched to a non–platinum-based regimen after the onset of hypersensitivity. [ABSTRACT FROM AUTHOR]

Midostaurin is a multitargeted tyrosine kinase inhibitor approved by the Food and Drug Administration for FMS-related tyrosine kinase 3-positive acute myeloid leukemia in combination with standard daunorubicin and cytarabine induction and high-dose cytarabine consolidation. The pharmacokinetics of midostaurin in the setting of severe renal impairment (creatinine clearance [CrCl] 15-29 mL/min utilizing Cockcroft-Gault method) and end-stage renal disease are unknown. Midostaurin is primarily metabolized by the liver through the CYP3A4 enzyme with fecal excretion accounting for 95% of the dose (4% recovered as unchanged drug). Only 5% of the parent drug is found in the urine. This is the first case report documenting the administration of midostaurin in two patients with end-stage renal disease on HD. Given the limited excretion of both active and inactive metabolites of midostaurin in the urine, one does not expect an increase in toxicity related to impaired drug excretion. Although this report describes the likely successful utilization of midostaurin, caution should be exercised when administering in patient populations with end organ disease. Medical history, concomitant comorbidities, and goals of therapy should be taken into account. [ABSTRACT FROM AUTHOR]

Introduction: Gilteritinib is a multitargeted tyrosine kinase inhibitor (TKI) approved by the Food and Drug Administration (FDA) for acute myeloid leukemia (AML) with a FMS-related tyrosine kinase 3 (FLT3) mutation. The pharmacokinetics of gilteritinib in the setting of severe renal impairment (creatinine clearance [CrCl] 15-29 mL/min utilizing Cockcroft-Gault method) and end-stage renal disease are unknown. Gilteritinib is primarily metabolized by the liver through the CYP3A4 enzyme and is eliminated in both the feces and urine. Its excretion is primarily through the fecal route, accounting for 64.5% of the recovered dose. Only about 16.4% of the recovered dose has been detected in the urine of human subjects. Case Report: We describe our patient case documenting the administration of gilteritinib in the setting of end-stage renal disease (ESRD) and hemodialysis (HD). Management and Outcomes: Our patient was initiated on single agent gilteritinib 120 mg by mouth once daily for relapse FLT3-TDK positive AML. Treatment course was complicated by pancytopenia, neutropenic fever, and staphylococcus lugdunensis bacteremia requiring temporary interruption of therapy. Discussion: Given that gilteritinib is metabolized by the liver and eliminated primarily in the feces, one does not expect an increase in toxicity related to impaired renal function. Although this report describes the successful utilization of gilteritinib, caution should be exercised when administering in patient populations with end organ disease, and patient comorbidities should be taken into account. [ABSTRACT FROM AUTHOR]

Midostaurin is the first approved FMS-related tyrosine kinase 3 (FLT3) inhibitor indicated for FLT3 mutated acute myeloid leukemia. Midostaurin is a major cytochrome P450 3A4 (CYP3A4) substrate. Coadministration with a strong CYP3A4 inhibitor or inducer can lead to a potential increase or decrease in midostaurin exposure. This report describes a 43-year-old patient with FLT3-internal tandem duplication (FLT3-ITD) positive acute myeloid leukemia who initially presented with leukocytosis and concern for acute leukemia. Following the initiation of induction chemotherapy, the patient developed lung nodules concerning for a fungal infection. Isavuconazole, a moderate CYP3A4 inhibitor, was successfully initiated and maintained, while midostaurin therapy was also administered. Clinicians should be aware and exercise caution when using midostaurin with CYP3A4 inhibitors and inducers. [ABSTRACT FROM AUTHOR]