10535 Background: ERI is an inhibitor of microtubule dynamics. IRI is used to treat pediatric sarcomas. In the pediatric preclinical testing program, ERI was well tolerated and had promising activity compared with vincristine (a common chemotherapeutic for pediatric cancers) for various solid tumors ( in vivo xenograft panels). Methods: Children with relapsed/refractory solid tumors (excluding active central nervous system tumors) were enrolled. Prior treatment with IRI was allowed. Dose escalation was conducted for 2 schedules with the primary objective (phase 1) of determining the maximum tolerated dose and the recommended phase 2 dose: (A) ERI 1.4 mg/m2 IV infusion (Days 1 + 8 of 21-day cycle) + IRI 20 or 40 mg/m2 IV infusion (Days 1–5 of 21-day cycle); (B) ERI 1.4 mg/m2 IV infusion (Days 1 + 8 of 21-day cycle) + IRI 100 or 125 mg/m2 IV infusion (Days 1 + 8 of 21-day cycle). Safety and pharmacokinetic parameters were assessed. Results: 13 patients (pts) were enrolled (median age: 9 years [range: 3–17]); 4 pts had rhabdomyosarcoma (RMS), 2 had non-RMS soft tissue sarcoma, 2 had Ewing sarcoma, 2 had hepatoblastoma, 2 had nephroblastoma, and 1 had neuroblastoma. Overall, 7 pts previously received IRI. No dose-limiting toxicities (DLTs) were reported for either schedule. At data cut-off (July 14, 2019), 4 pts (with Ewing sarcoma, neuroblastoma, RMS, or hepatoblastoma) continued treatment (A, n = 2; B, n = 2) and 9 pts discontinued treatment (primarily for radiographic progression, n = 7 [A, n = 4; B, n = 3]). All pts experienced ≥1 treatment-emergent adverse event (TEAE); the most common any grade TEAE was neutropenia (n = 10; A, n = 5; B, n = 5). 11 pts had grade ≥3 TEAEs (A, n = 6; B, n = 5); the most frequent grade ≥3 TEAE was neutropenia (n = 9; A, n = 5; B, n = 4). No pt withdrew ERI or IRI due to an AE; 3 pts had dose reductions for ERI (A, n = 1; B, n = 2) and 3 pts had dose interruption of ERI (A, n = 2; B, n = 1) due to AEs. No pt had dose reductions for IRI, and 3 pts had dose interruption of IRI (A, n = 2; B, n = 1) due to AEs. 3 deaths occurred; 2 deaths were the result of tumor progression (A, n = 1; B, n = 1), and the cause of 1 was unknown (B). 1 pt with neuroblastoma treated according to schedule A had a partial response. Systemic exposures of ERI, IRI, and SN-38 (IRI active metabolite) were similar between schedules and doses. Conclusions: No DLTs were observed. Toxicity was manageable. Administration of IRI treatment on Days 1–5 is widely used in pediatric cancers; enrollment for phase 2 is ongoing with treatment Schedule A (ERI 1.4 mg/m2 Days 1 + 8 of 21-day cycle; IRI 40 mg/m2 Days 1–5 of 21-day cycle). Clinical trial information: NCT03245450.
Introduction The analysis of urinary catecholamine metabolites is a cornerstone of neuroblastoma diagnostics. Currently, there is no consensus regarding the sampling method, and variable combinations of catecholamine metabolites are being used. We investigated if spot urine samples can be reliably used for analysis of a panel of catecholamine metabolites for the diagnosis of neuroblastoma. Methods Twenty‐four‐hour urine or spot urine samples were collected from patients with and without neuroblastoma at diagnosis. Homovanillic acid (HVA), vanillylmandelic acid (VMA), dopamine, 3‐methoxytyramine, norepinephrine, normetanephrine, epinephrine and metanephrine were measured by high‐performance liquid chromatography coupled with fluorescence detection (HPLC‐FD) and/or ultra‐performance liquid chromatography coupled with electrospray tandem mass spectrometry (UPLC‐MS/MS). Results Catecholamine metabolite levels were measured in urine samples of 400 neuroblastoma patients (24‐hour urine, n = 234; spot urine, n = 166) and 571 controls (all spot urine). Excretion levels of catecholamine metabolites and the diagnostic sensitivity for each metabolite were similar in 24‐hour urine and spot urine samples (p > .08 and >.27 for all metabolites). The area under the receiver‐operating‐characteristic curve (AUC) of the panel containing all eight catecholamine metabolites was significantly higher compared to that of only HVA and VMA (AUC = 0.952 vs. 0.920, p = .02). No differences were observed in metabolite levels between the two analysis methods. Conclusion Catecholamine metabolites in spot urine and 24‐hour urine resulted in similar diagnostic sensitivities. The Catecholamine Working Group recommends the implementation of spot urine as standard of care. The panel of eight catecholamine metabolites has superior diagnostic accuracy over VMA and HVA.
Background: Oral anticancer agents (OAAs) can be effective in cancer control, but patients should conduct adequate self-care in managing OAAs and related toxicities to improve their quality of life. However, tools are lacking for measuring self-care behaviours in cancer patients on OAAs. The aim of this study was to develop a new selfreported instrument, the Self-Care of Oral Anticancer Agents Index (SCOAAI) and to test its content validity.Methods: SCOAAI items were developed according to the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) criteria. The Middle Range Theory of Self-Care of Chronic Illnesses was used to guide item development, including self-care maintenance (i.e. behaviours to maintain condition stability), self-care monitoring (i.e. behaviours to monitor OAAs side effects) and selfcare management (i.e. patients' responses to deal with OAAs side effects). A literature review and qualitative interviews with patients and healthcare professionals were conducted to develop SCOAAI-specific items and to assess their comprehensibility and comprehensiveness. The Content Validity Index (CVI) was calculated.Results: A first version of the SCOAAI included 44 items. Patients participating in the cognitive interviews (n¼12; n¼6 women, mean age 65 years [SD AE 8]; 37.5% with lung cancer) deemed the instructions, items and response options to be comprehensible and comprehensive. Face-to-face interviews with 5 experts (n¼3 female, mean age: 52 years [SD AE 12.28], n¼4 physicians) addressed some issues of the instrument, resulting in removal of 12 items. The final version of the SCOAAI included 32 items: 15 in self-care maintenance, 11 in self-care monitoring and 6 in self-care management. The item CVI ranged between 0.8 and 1; the scale CVI was 0.99. Conclusions:The SCOAAI showed good content validity and is a promising and psychometrically sound instrument for the assessment of self-care behaviours of cancer patients on OAAs. Since better self-care is associated with better clinical outcomes (e.g. less toxicity, better quality of life and fewer hospitalisations), the SCOAAI, once validated, could become a useful instrument for use in oncology clinical practice and research.Legal entity responsible for the study: M. Di Nitto.Funding: "Lega Italiana per la Lotta contro i Tumori" (LILT) foundation.
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