Phase I/II study of single-agent lenvatinib in children and adolescents with refractory or relapsed solid malignancies and young adults with osteosarcoma (ITCC-050)☆.

BACKGROUND: We report results from the phase I dose-finding and phase II expansion part of a multicenter, open-label study of single-agent lenvatinib in pediatric and young adult patients with relapsed/refractory solid tumors, including osteosarcoma and radioiodine-refractory differentiated thyroid cancer (RR-DTC) (NCT02432274). PATIENTS AND METHODS: The primary endpoint of phase I was to determine the recommended phase II dose (RP2D) of lenvatinib in children with relapsed/refractory solid malignant tumors. Phase II primary endpoints were progression-free survival rate at 4 months (PFS-4) for patients with relapsed/refractory osteosarcoma; and objective response rate/best overall response for patients with RR-DTC at the RP2D. RESULTS: In phase I, 23 patients (median age, 12 years) were enrolled. With lenvatinib 14 mg/m2, three dose-limiting toxicities (hypertension, n = 2; increased alanine aminotransferase, n = 1) were reported, establishing 14 mg/m2 as the RP2D. In phase II, 31 patients with osteosarcoma (median age, 15 years) and 1 patient with RR-DTC (age 17 years) were enrolled. For the osteosarcoma cohort, PFS-4 (binomial estimate) was 29.0% [95% confidence interval (CI) 14.2% to 48.0%; full analysis set: n = 31], PFS-4 by Kaplan-Meier estimate was 37.8% (95% CI 20.0% to 55.4%; full analysis set) and median PFS was 3.0 months (95% CI 1.8-5.4 months). The objective response rate was 6.7% (95% CI 0.8% to 22.1%). The patient with RR-DTC had a best overall response of partial response. Some 60.8% of patients in phase I and 22.6% of patients in phase II (with osteosarcoma) had treatment-related treatment-emergent adverse events of grade ≥3. CONCLUSIONS: The lenvatinib RP2D was 14 mg/m2. Single-agent lenvatinib showed activity in osteosarcoma; however, the null hypothesis could not be rejected. The safety profile was consistent with previous tyrosine kinase inhibitor studies. Lenvatinib is currently being investigated in osteosarcoma in combination with chemotherapy as part of a randomized, controlled trial (NCT04154189), in pediatric solid tumors in combination with everolimus (NCT03245151), and as a single agent in a basket study with enrollment ongoing (NCT04447755).

Risk Factors for Chronic Kidney Disease in Newly Diagnosed Hypertensive Subjects in Southeast Nigeria.

BACKGROUND: The aim of this study was to determine the prevalence and associated risk factors for chronic kidney disease (CKD) in newly diagnosed hypertensive patients. MATERIALS AND METHODS: This was a cross-sectional analytical study involving consenting newly diagnosed hypertensive patients who presented at GOPD of Federal Medical Centre, Umuahia, within 0-3 months of diagnosis; and non-hypertensive controls. A semi-structured interviewer- administered questionnaire was used to record the socio-demographic, anthropometric, clinical and bio-chemical characteristics of the respondents. Data were analyzed and compared between the hypertensive group and the non-hypertensive control group. RESULTS: Two hundred and sixty participants took part in the study. However, only 240 completed the study (120 hypertensive, and 120 control participants). After follow-up for 3 months, 42 (35.0%) hypertensive patients had CKD compared to 11 (9.2%) of the non-hypertensive control group. The prevalence of CKD in the hypertensive participants was significantly higher (2=23.27, p<0.001). Multivariate regression analysis of CKD with variables in the hypertensive study group showed an association between CKD and sex (p=0.020), serum triglycerides (p=0.030) as well as serum uric acid (p=0.030). In the control group there was significant association between CKD and sex (p=0.020), serum total cholesterol (p=0.030) as well as serum uric acid (p=0.030). CONCLUSION: The prevalence of CKD among newly diagnosed hypertensives in southeast Nigeria was high. In this group, CKD had an association with sex, serum uric acid and serum triglyceride.

The socioeconomic impact of burns in Lagos, Nigeria: a one-year prospective study.

A one-year prospective study of burn patients presenting to the National Orthopaedic Hospital, Igbobi, Lagos from June 1, 2007 to May 31, 2008 was conducted to evaluate the socioeconomic impact of burn injuries sustained by the patients. A proforma reflecting the various data of interest was the main instrument of the study. The data was subjected to simple statistical analysis. A total of 52 patients with a mean age of 25 ± 17.1 years were studied. There were 27 males and 25 females giving a M:F ratio of 1.1:1. Man-hours were lost by 88.5% of the patients, 55.8% of whom were income earners. About 74% of the patients had returned to work or school at the conclusion of the study. The most common opportunity cost of treatment was a relative stopping work or school. Half of the patients were unsatisfied with their appearance and 26.9% desired cosmetic surgery. Social interactions were normal in 74.5% of the patients and none reported a poor quality of life. The study showed a significant socioeconomic burden from burns. It highlighted the importance of the informal sociocultural support system and the need for formal, well-structured social support systems.

Une étude prospective concernant les patients brûlés se présentant à l'hôpital orthopédique national Igobi de Lagos entre le 1er juin 2007 et le 31 mai 2008 a été conduite afin d'évaluer l'impact socio-économique de leur blessure. Une feuille de recueil des données à étudier a été utilisée, les variables étant ensuite analysées. Cinquante deux patients de 25 ± 17,1 ans ont été inclus. Il y avait 27 hommes et 25 femmes soit un sex-ratio de 1,1:1. Un arrêt de travail a été nécessaire pour 88,5 % des patients dont 55,8 % étaient soutien de famille. A peu près les 3/4 des patients avaient repris le travail ou l'école à la fin de l'étude, cet arrêt d'activité représentant l'essentiel des coûts indirects. La moitié des patients souffraient de leur apparence et 26,9 % désiraient une prise en charge de chirurgie plastique. La vie sociale était normale pour 74,5 % des patients, aucun d'eux ne se plaignait d'une mauvaise qualité de vie. L'étude a montré un impact socio-économique significatif des brûlures. Elle a permis de souligner l'importance du rôle de soutien du système socio-culturel informel et donc la nécessité d'en développer un officiel.