A randomized double-blind placebo-controlled trial of the effectiveness of melatonin on neurocognition and sleep in survivors of childhood cancer.

BACKGROUND: Adult survivors of childhood cancer are at risk of developing sleep and neurocognitive problems, yet few efficacious interventions exist targeting these prevalent late effects. Melatonin has known sleep-promoting effects; however, it has not been well studied among childhood cancer survivors. METHOD: Survivors (n = 580; mean age = 33.5 years; 26 years post-diagnosis) from the St. Jude Lifetime Cohort were randomized (1:1) to a six-month double-blind placebo-controlled trial of 3 mg time-release melatonin within three strata (stratum 1: neurocognitive impairment only; stratum 2: neurocognitive and sleep impairment; stratum 3: sleep impairment only). Neurocognitive performance was assessed at baseline and post-intervention using standardized measures. Sleep was assessed via self-report and actigraphy. Independent sample t tests compared mean change scores from baseline to six months. Post-hoc analyses compared the prevalence of clinically significant treatment responders among melatonin and placebo conditions within and across strata. RESULTS: Intent-to-treat analyses revealed no statistically significant differences in neurocognitive performance or sleep from baseline to post-intervention. However, among survivors with neurocognitive impairment only, a larger proportion randomized to melatonin versus placebo demonstrated a treatment response for visuomotor speed (63% vs 41%, P = 0.02) and nonverbal reasoning (46% vs 28%, P = 0.04). Among survivors with sleep impairment only, a larger proportion treated with melatonin demonstrated a treatment response for shifting attention (44% vs 28%, P = 0.05), short-term memory (39% vs 19%, P = 0.01), and actigraphy-assessed sleep duration (47% vs 29%, P = 0.05). CONCLUSION: Melatonin was not associated with improved neurocognitive performance or sleep in our intent-to-treat analyses; however, a subset of survivors demonstrated a clinically significant treatment response.

Safety, tolerability, pharmacokinetics, and antimalarial efficacy of a novel Plasmodium falciparum ATP4 inhibitor SJ733: a first-in-human and induced blood-stage malaria phase 1a/b trial.

BACKGROUND: (+)-SJ000557733 (SJ733) is a novel, orally bioavailable inhibitor of Plasmodium falciparum ATP4. In this first-in-human and induced blood-stage malaria phase 1a/b trial, we investigated the safety, tolerability, pharmacokinetics, and antimalarial activity of SJ733 in humans. METHODS: The phase 1a was a single-centre, dose-escalation, first-in-human study of SJ733 allowing modifications to dose increments and dose-cohort size on the basis of safety and pharmacokinetic results. The phase 1a took place at St Jude Children's Research Hospital and at the University of Tennessee Clinical Research Center (Memphis, TN, USA). Enrolment in more than one non-consecutive dose cohort was allowed with at least 14 days required between doses. Participants were fasted in seven dose cohorts and fed in one 600 mg dose cohort. Single ascending doses of SJ733 (75, 150, 300, 600, 900, or 1200 mg) were administered to participants, who were followed up for 14 days after SJ733 dosing. Phase 1a primary endpoints were safety, tolerability, and pharmacokinetics of SJ733, and identification of an SJ733 dose to test in the induced blood-stage malaria model. The phase 1b was a single-centre, open-label, volunteer infection study using the induced blood-stage malaria model in which fasted participants were intravenously infected with blood-stage P falciparum and subsequently treated with a single dose of SJ733. Phase 1b took place at Q-Pharm (Herston, QLD, Australia) and was initiated only after phase 1a showed that exposure exceeding the threshold minimum exposure could be safely achieved in humans. Participants were inoculated on day 0 with P falciparum-infected human erythrocytes (around 2800 parasites in the 150 mg dose cohort and around 2300 parasites in the 600 mg dose cohort), and parasitaemia was monitored before malaria inoculation, after inoculation, immediately before SJ733 dosing, and then post-dose. Participants were treated with SJ733 within 24 h of reaching 5000 parasites per mL or at a clinical score higher than 6. Phase 1b primary endpoints were calculation of a parasite reduction ratio (PRR48) and parasite clearance half-life, and safety and tolerability of SJ733 (incidence, severity, and drug-relatedness of adverse events). In both phases of the trial, SJ733 hydrochloride salt was formulated as a powder blend in capsules containing 75 mg or 300 mg for oral administration. Healthy men and women (of non-childbearing potential) aged 18-55 years were eligible for both studies. Both studies are registered with ClinicalTrials.gov (NCT02661373 for the phase 1a and NCT02867059 for the phase 1b). FINDINGS: In the phase 1a, 23 healthy participants were enrolled and received one to three non-consecutive doses of SJ733 between March 14 and Dec 7, 2016. SJ733 was safe and well tolerated at all doses and in fasted and fed conditions. 119 adverse events were recorded: 54 (45%) were unrelated, 63 (53%) unlikely to be related, and two (2%) possibly related to SJ733. In the phase 1b, 17 malaria-naive, healthy participants were enrolled. Seven participants in the 150 mg dose cohort were inoculated and dosed with SJ733. Eight participants in the 600 mg dose cohort were inoculated, but two participants could not be dosed with SJ733. Two additional participants were subsequently inoculated and dosed with SJ733. SJ733 exposure increased proportional to the dose through to the 600 mg dose, then was saturable at higher doses. Fasted participants receiving 600 mg exceeded the target area under the concentration curve extrapolated to infinity (AUC0-∞) of 13 000 µg × h/L (median AUC0-∞ 24 283 [IQR 16 135-31 311] µg × h/L, median terminal half-life 17·4 h [IQR 16·1-24·0], and median timepoint at which peak plasma concentration is reached 1·0 h [0·6-1·3]), and this dose was tested in the phase 1b. All 15 participants dosed with SJ733 had at least one adverse event. Of the 172 adverse events recorded, 128 (74%) were mild. The only adverse event attributed to SJ733 was mild bilateral foot paraesthesia that lasted 3·75 h and resolved spontaneously. The most common adverse events were related to malaria. Based on parasite clearance half-life, the derived log10PRR48 and corresponding parasite clearance half-lives were 2·2 (95% CI 2·0-2·5) and 6·47 h (95% CI 5·88-7·18) for 150 mg, and 4·1 (3·7-4·4) and 3·56 h (3·29-3·88) for 600 mg. INTERPRETATION: The favourable pharmacokinetic, tolerability, and safety profile of SJ733, and rapid antiparasitic effect support its development as a fast-acting component of combination antimalarial therapy. FUNDING: Global Health Innovative Technology Fund, Medicines for Malaria Venture, and the American Lebanese Syrian Associated Charities.

Addressing challenges of clinical trials in acute pain: The Pain Management of Vaso-occlusive Crisis in Children and Young Adults with Sickle Cell Disease Study.

BACKGROUND/AIMS: Neuropathic pain is a known component of vaso-occlusive pain in sickle cell disease; however, drugs targeting neuropathic pain have not been studied in this population. Trials of acute pain are complicated by the need to obtain consent, to randomize participants expeditiously while optimally treating pain. We describe the challenges in designing and implementing the Pain Management of Vaso-occlusive Crisis in Children and Young Adults with Sickle Cell Disease Study (NCT01954927), a phase II, randomized, double-blind, placebo-controlled trial to determine the effect of gabapentin for vaso-occlusive crisis. METHODS: In the Pain Management of Vaso-occlusive Crisis in Children and Young Adults with Sickle Cell Disease Study, we aim to assess the analgesic effect of gabapentin during vaso-occlusive crisis. Difficulties we identified included avoiding delay of notification of study staff of potential participants which we resolved by automated notification. Concern for rapid randomization and drug dispensation was addressed through careful planning with an investigational pharmacy and a single liquid formulation. We considered obtaining consent during well-visits to avoid the time constraints with acute presentations, but the large number of patients and limited duration that consent is valid made this impractical. RESULTS: In all, 79% of caregivers/children approached have agreed to participate. The trial is currently active, and enrollment is at 45.8% of that targeted (76 of 166) and expected to continue for two more years. Maintaining staff availability after-hours remains problematic, with 8% of screened patients missed for lack of available staff. LESSONS LEARNED: Lessons learned in designing a trial to expedite procedures in the acute pain setting include (1) building study evaluations upon a standard-of-care backbone; (2) implementing a simple study design to facilitate consent and data capture; (3) assuring ample, well-trained study staff; and (4) utilizing technology to automate procedures whenever possible. CONCLUSION: This study design has circumvented many of the logistical barriers usually associated with acute pain trials and may serve as a prototype for future studies.

Efficacy of glucarpidase (carboxypeptidase g2) in patients with acute kidney injury after high-dose methotrexate therapy.

STUDY OBJECTIVE: Because the incidence rate of renal impairment is 2-10% for patients treated with high-dose methotrexate and renal impairment develops in 0-12.4% of patients treated for osteosarcoma, we sought to evaluate the efficacy of glucarpidase, a recently approved drug that rapidly hydrolyzes methotrexate to inactive metabolites, which allows for nonrenal clearance in patients with delayed renal methotrexate elimination. DESIGN: Pooled analysis of efficacy data from four multicenter single-arm compassionate-use clinical trials using protocols from 1993 to 2007. PATIENTS: Of 476 patients with renal toxicity and delayed methotrexate elimination who were treated with intravenous glucarpidase for rescue after high-dose methotrexate, 169 patients had at least one preglucarpidase (baseline) plasma methotrexate concentration greater than 1 µmol/L and one postglucarpidase methotrexate concentration measurement by high-performance liquid chromatography and were included in the efficacy analysis; renal recovery was assessed in 436 patients who had at least one recorded preglucarpidase and postglucarpidase serum creatinine concentration measurement. MEASUREMENTS AND MAIN RESULTS: Efficacy was defined as rapid and sustained clinically important reduction (RSCIR) in plasma methotrexate concentration, with a concentration of 1 µmol/L or lower at all postglucarpidase determinations. Median age of efficacy-evaluable patients was 20 years (range 5 weeks-84 years). Osteosarcoma (36%), non-Hodgkin lymphoma (27%), and acute lymphoblastic leukemia (20%) were the most frequent underlying diagnoses. Median preglucarpidase serum methotrexate was 11.7 µmol/L. At the first (median 15 minutes) through the last (median 40 hours) postglucarpidase measurement, plasma methotrexate concentrations demonstrated consistent 99% median reduction. RSCIR was achieved by 83 (59%) of 140 patients. A total of 64% of patients with renal impairment greater than or equal to Common Terminology Criteria for Adverse Events grade 2 recovered to grade 0 or 1 at a median of 12.5 days after glucarpidase administration. CONCLUSION: Glucarpidase caused a clinically important 99% or greater sustained reduction of serum methotrexate levels and provided noninvasive rescue from methotrexate toxicity in renally impaired patients.

Alternative formulations of sorafenib for use in children.

BACKGROUND: Sorafenib is an oral multikinase inhibitor with antiangiogenic and antitumor activity. In most cases, the commercially available 200 mg tablet is not suitable for administration to children. We studied the chemical and physical stability of extemporaneously prepared formulations and evaluated the pharmacokinetic profile of cut tablets and smaller-dosage capsules of sorafenib in children. PROCEDURE: Commercially available 200 mg tablets of sorafenib tosylate were used to prepare liquid suspensions of sorafenib in oil and Ora-Plus(®):Ora-Sweet(®) solution, and to prepare 5, 10, 20, 50, and 100 mg capsules. Plasma concentrations of sorafenib were measured in patients receiving capsules and cut tablets, using a validated HPLC-based method with tandem mass spectrometric detection. RESULTS: At room temperature and under refrigeration, sorafenib concentrations in Ora Plus(®):Ora Sweet(®) were highly variable (means ranging from 75% to 131% of the intended concentration of 50 mg/ml). In oil suspension, sorafenib concentrations were inconsistent during compounding. In contrast, all smaller-dosage capsules, except the 5 mg capsule, were within 91-99% of the intended content and were stable at room temperature for at least 8 months. Sorafenib pharmacokinetic parameters in patients receiving capsules or cut tablets were consistent with those reported previously in adults and children receiving intact tablets. CONCLUSIONS: Sorafenib is not stable in an oral suspension prepared from commercially available tablets, but compounded capsules in smaller-dosage forms that can be sprinkled on food or cut tablets are alternatives for administration to children who need smaller doses based on body surface area or cannot swallow tablets.

Phase I pharmacokinetic and pharmacodynamic study of the multikinase inhibitor sorafenib in combination with clofarabine and cytarabine in pediatric relapsed/refractory leukemia.

PURPOSE: To assess the toxicity, pharmacokinetics, and pharmacodynamics of multikinase inhibitor sorafenib in combination with clofarabine and cytarabine in children with relapsed/refractory leukemia. PATIENTS AND METHODS: Twelve patients with acute leukemia (11 with acute myeloid leukemia [AML]) received sorafenib on days 1 to 7 and then concurrently with cytarabine (1 g/m(2)) and clofarabine (stratum one: 40 mg/m(2), n = 10; stratum two [recent transplantation or fungal infection]: 20 mg/m(2), n = 2) on days 8 to 12. Sorafenib was continued until day 28 if tolerated. Two sorafenib dose levels (200 mg/m(2) and 150 mg/m(2) twice daily) were planned. Sorafenib pharmacokinetic and pharmacodynamic studies were performed on days 7 and 8. RESULTS: At sorafenib 200 mg/m(2), two of four patients in stratum one and one of two patients in stratum two had grade 3 hand-foot skin reaction and/or rash as dose-limiting toxicities (DLTs). No DLTs were observed in six patients in stratum one at sorafenib 150 mg/m(2). Sorafenib inhibited the phosphorylation of AKT, S6 ribosomal protein, and 4E-BP1 in leukemia cells. The rate of sorafenib conversion to its metabolite sorafenib N-oxide was high (mean, 33%; range, 17% to 69%). In vitro, the N-oxide potently inhibited FLT3-internal tandem duplication (ITD; binding constant, 70 nmol/L) and the viability of five AML cell lines. On day 8, sorafenib decreased blast percentages in 10 of 12 patients (median, 66%; range, 9% to 95%). After combination chemotherapy, six patients (three FLT3-ITD and three FLT3 wild-type AML) achieved complete remission, two (both FLT3-ITD AML) had complete remission with incomplete blood count recovery, and one (FLT3 wild-type AML) had partial remission. CONCLUSION: Sorafenib in combination with clofarabine and cytarabine is tolerable and shows activity in relapsed/refractory pediatric AML.

Long-term efficacy of methylphenidate in enhancing attention regulation, social skills, and academic abilities of childhood cancer survivors.

PURPOSE: Methylphenidate (MPH) ameliorates attention problems experienced by some cancer survivors in the short term, but its long-term efficacy is unproven. PATIENTS AND METHODS: This study investigates the long-term effectiveness of maintenance doses of MPH in survivors of childhood brain tumors (n = 35) and acute lymphoblastic leukemia (n = 33) participating in a 12-month MPH trial. Measures of attention (Conners' Continuous Performance Test [CPT], Conners' Rating Scales [CRS]), academic abilities (Wechsler Individual Achievement Test [WIAT]), social skills (Social Skills Rating System [SSRS]), and behavioral problems (Child Behavior Checklist [CBCL]) were administered at premedication baseline and at the end of the MPH trial while on medication. A cancer control group composed of patients who were not administered MPH (brain tumor = 31 and acute lymphoblastic leukemia = 23) was assessed on the same measures 12 [corrected] months apart. RESULTS: For the MPH group, repeated measures analysis of variance revealed significant improvement in performance on a measure of sustained attention (CPT indices, P < .05); parent, teacher, and self-report ratings of attention (CRS indices, P < .05), and parent ratings of social skills or behavioral problems (SSRS and CBCL indices; P < .05). In contrast, the cancer control group only showed improvement on parent ratings of attention (Conners' Parent Rating Scale indices; P < .05) and social skills (SSRS and CBCL indices; P < .05). There was no significant improvement on the academic measure (WIAT) in either group. CONCLUSION: Attention and behavioral benefits of MPH for childhood cancer survivors are maintained across settings over the course of a year. Although academic gains were not identified, MPH may offer benefits in academic areas not assessed.

Stability of cyclophosphamide in extemporaneous oral suspensions.

BACKGROUND: Cyclophosphamide, an alkylating agent, is widely used for the treatment of many adult and pediatric malignancies. The stability of cyclophosphamide in aqueous- and methylcellulose-based oral suspending vehicles is currently unknown. OBJECTIVE: To develop and validate a stability-indicating high-performance liquid chromatography (HPLC) method to measure cyclophosphamide concentrations in simple syrup and Ora-Plus, and assess the 56-day chemical stability and physical appearance of cyclophosphamide in these suspensions at both room temperature (22 degrees C) and 4 degrees C. METHODS: The intravenous formulation of cyclophosphamide was diluted to 20 mg/mL in NaCl 0.9%, compounded 1:1 with either suspending vehicle, and stored in the dark in 3-mL amber polypropylene oral syringes at 4 degrees C and 22 degrees C. Aliquots from each syringe were obtained on days 0, 3, 7, 14, 21, 28, 35, 42, 49, and 56 and assayed using the validated stability-indicating HPLC-UV method. A C18 analytical column was used to separate cyclophosphamide from the internal standard, ifosfamide, with a mobile phase of 21% acetonitrile in 79% sodium phosphate buffer. The suspension was examined for odor change, visually examined under normal fluorescent light for color change, and examined under a light microscope for evidence of microbial growth. RESULTS: Samples of cyclophosphamide in both simple syrup and Ora-Plus were stable when kept at 4 degrees C for at least 56 days. At room temperature, cyclophosphamide in simple syrup and Ora-Plus had a shelf life of 8 and 3 days, respectively. No changes in color or odor or evidence of microbial growth were observed. CONCLUSIONS: Cyclophosphamide can be extemporaneously prepared in simple syrup or Ora-Plus and stored for at least 2 months under refrigeration without significant degradation.

Stability of sunitinib in oral suspension.

BACKGROUND: Sunitinib is a novel, oral, multitargeted tyrosine kinase inhibitor with antiangiogenic and antitumor activity. No liquid formulation of sunitinib malate is commercially available for pediatric administration. OBJECTIVE: To prepare extemporaneously an oral liquid formulation of sunitinib malate from commercially available capsules and study its chemical and physical stability in suspension at room temperature and under refrigeration at 4 degrees C. METHODS: Six independent samples were prepared by mixing the contents of 3 sunitinib malate capsules (each equivalent to 50 mg of sunitinib) with 15 mL of a 1:1 mixture of Ora-Plus:Ora-Sweet solution to yield a final concentration of 10 mg/mL. Suspensions were stored in amber plastic bottles with child-resistant caps. Three samples were refrigerated at 4 degrees C and 3 were stored at room temperature. Aliquots from each bottle were obtained on days 1, 2, 3, 5, 7, 14, 21, 30, and 60 and diluted to a final concentration of 300 ng/mL with 500 ng/mL of clozapine in 50% acetonitrile. Sunitinib concentrations were then measured by a liquid chromatography-tandem mass spectrometry assay validated in our laboratory. RESULTS: At room temperature and under refrigeration at 4 degrees C, sunitinib in a 10-mg/mL suspension of sunitinib malate with Ora-Plus:Ora-Sweet 1:1 maintained greater than 96% of its initial concentration for 60 days. Visual appearance (color and consistency) and odor of drug suspension remained unchanged during the study. CONCLUSIONS: Sunitinib is stable in an oral suspension prepared from commercially available capsules for at least 60 days at room temperature and refrigeration at 4 degrees C. This liquid formulation is better suited for administration to children and adults with cancer who cannot swallow sunitinib capsules.

Acute neurocognitive response to methylphenidate among survivors of childhood cancer: a randomized, double-blind, cross-over trial.

OBJECTIVE: To investigate the acute efficacy and adverse side effects of methylphenidate (MPH) among survivors of childhood cancer [acute lymphoblastic leukemia (ALL) or brain tumor (BT)] with learning impairments. METHODS: Participants (N = 122) completed a two-day, in-clinic, double-blind, cross-over trial during which they received MPH (0.60 mg/kg of body weight) and placebo that were randomized in administration order across participants. Performance was evaluated using measures of attention, memory, and academic achievement. RESULTS: A significant MPH versus placebo effect was revealed on a measure of attention, cognitive flexibility, and processing speed (Stroop Word-Color Association Test). Male gender, older age at treatment, and higher intelligence were predictive of better medication response. No significant differences were found for number or severity of adverse side effects as a function of active medication. CONCLUSIONS: MPH shows some neurocognitive benefit and is well tolerated by the majority of children surviving ALL and BT.

Smaller white-matter volumes are associated with larger deficits in attention and learning among long-term survivors of acute lymphoblastic leukemia.

BACKGROUND: The primary objective of this study was to test the hypothesis that survivors of childhood acute lymphoblastic leukemia (ALL) have deficits in neurocognitive performance, and smaller white-matter volumes are associated with these deficits. METHODS: The patients studied included 112 ALL survivors (84 patients who had received chemotherapy only, 28 patients who had received chemotherapy and irradiation; 63 males, 49 females; mean age +/- standard deviation, 4.1 yrs +/- 2.6 yrs at diagnosis; mean +/- standard deviation yrs since diagnosis, 6.0 +/- 3.5 yrs), and 33 healthy siblings who participated as a control group. Neurocognitive tests of attention, intelligence, and academic achievement were performed; and magnetic resonance images were obtained and subsequently were segmented to yield tissue volume measurements. Comparisons of neurocognitive measures and tissue volumes between groups were performed, and the correlations between volumes and neurocognitive performance measures were assessed. RESULTS: Most performance measures demonstrated statistically significant differences from the normative test scores, but only attention measures exceeded 1.0 standard deviation from normal. Patients who had received chemotherapy alone had significantly larger volumes of white matter than patients who had received treatment that also included cranial irradiation, but their volumes remained significantly smaller than the volumes in the control group. Smaller white-matter volumes were associated significantly with larger deficits in attention, intelligence, and academic achievement. CONCLUSIONS: Survivors of childhood ALL had significant deficits in attention and smaller white-matter volumes that were associated directly with impaired neurocognitive performance. Cranial irradiation exacerbated these deficits.

Short-term efficacy of methylphenidate: a randomized, double-blind, placebo-controlled trial among survivors of childhood cancer.

PURPOSE: Children surviving acute lymphoblastic leukemia (ALL) and malignant brain tumors (BTs) have a higher incidence of attention and learning problems in school than do their healthy peers. The present study tests the hypothesis that the psychostimulant methylphenidate (MPH) improves cognitive and social functioning among these patients. PATIENTS AND METHODS: We report on 83 long-term survivors of ALL and BT identified as having attentional deficits on behavioral testing and parent or teacher report, and problems with academic achievement. The 47 male and 36 female patients ranged from 0.6 to 14.3 years (median, 5.4 years) of age at diagnosis and 6.7 to 17.9 years (median, 11.9 years) of age at participation. The patients (40 ALL, 43 BT) participated in a randomized, double-blind, 3-week home cross-over trial of placebo (bid), low-dose MPH (0.3 mg/kg; maximum dose, 10 mg bid), and moderate-dose MPH (0.6 mg/kg; maximum dose, 20 mg bid). The primary end points were weekly teacher and parent reports on the Conners' Rating Scales and Social Skills Rating System. RESULTS: Compared to placebo, significant improvement with MPH was reported by teachers and parents on the Conners' Rating Scales and by teachers on the Social Skills Rating System. However, no consistent advantage of moderate dose over low dose was observed. Of those participating, 66 (79.5%) of the 83 patients continued on best clinical management. CONCLUSION: Treatment with MPH can at least temporarily reduce some attentional and social deficits among survivors of childhood ALL and BT. Long-term follow-up will reveal those subsets of patients who are more likely to benefit from MPH.

Octreotide therapy of pediatric hypothalamic obesity: a double-blind, placebo-controlled trial.

Hypothalamic obesity is a devastating complication in children surviving brain tumors and/or cranial irradiation. These subjects are thought to exhibit autonomic dysregulation of the beta-cell, with insulin hypersecretion in response to oral glucose tolerance testing (OGTT). We report the results of a randomized, double-blind, placebo-controlled trial of octreotide therapy for pediatric hypothalamic obesity. Eighteen subjects [weight, 100.6 +/- 5.6 kg; body mass index (BMI), 37.1 +/- 1.3 kg/m(2)] received octreotide (5-15 microg/kg x d s.c.) or placebo for 6 months. With octreotide, Delta weight (mean +/- SEM) was +1.6 +/- 0.6 vs. +9.1 +/- 1.7 kg for placebo (P < 0.001). Delta BMI was -0.2 +/- 0.2 vs. +2.2 +/- 0.5 kg/m(2), respectively (P < 0.001). OGTT documented Delta insulin response (peak - basal) of -417 +/- 304 pM after octreotide vs. +216 +/- 215 pM after placebo (P = 0.034). Improvement in physical activity by parent report was noted with octreotide, but not placebo (P = 0.03). For the octreotide group, changes in quality of life positively correlated with changes in insulin response (P = 0.041). Complications and adverse events were mild and self-limited. These data demonstrate the beneficial effects of octreotide in pediatric hypothalamic obesity. Octreotide suppressed insulin, and stabilized weight and BMI. Improved quality of life correlated with the degree of insulin suppression. Octreotide was safe and well tolerated.