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1.
Artículo en Inglés | MEDLINE | ID: mdl-38808497

RESUMEN

This cross-sectional study described prevalent body image (BI) concerns among adolescents and young adults (AYAs) with neoplasms who received treatment at a quaternary care children's hospital. Thirty-two AYAs, aged 15-39 years, completed questionnaires assessing BI within six months of diagnosis. The most frequently endorsed questionnaire items included the following: desire for increased physical fitness (62.5%), self-consciousness about hair (45.2%), weight dissatisfaction (40.6%), lack of strength (37.5%), wearing loose clothing to hide one's body (37.5%), decreased agility (34.4%), shape dissatisfaction (32.2%), and self-perception of too much body fat (31.3%). Awareness of AYA BI concerns during treatment may generate early intervention targeting this complex issue.

2.
Contemp Clin Trials ; 139: 107483, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38431133

RESUMEN

BACKGROUND: Medication non-adherence is common among adolescents and young adults (AYAs) with cancer and associated with poor health outcomes. AYAs with cancer endorse multiple barriers to adherence that differ across individuals, suggesting that tailoring intervention content to an AYA's specific barriers may have the potential to improve adherence. The purpose of this manuscript is to report on ORBIT-guided Phase I design efforts to create the first tailored adherence-promotion intervention for AYAs with cancer and the study protocol for the ongoing Phase II pilot feasibility trial. METHODS: Phase I design included qualitative interviews (n = 15 AYAs) to understand patient preferences for adherence-promotion care, development and refinement of a best-worst scaling exercise barriers tool (n = 5 AYAs), and development of intervention modules and a tailoring algorithm. In the ongoing Phase II pilot feasibility trial, AYAs (ages 15-24 years) with cancer currently taking oral chemotherapy or prophylactic medication will be recruited from three children's hospitals. Feasibility, acceptability, and usability will be assessed and these outcomes along with data on medication adherence will be used to inform the next phases of intervention development and testing. CONCLUSIONS: If promising, this program of research ultimately has the potential to equip clinicians with additional strategies for supporting adherence among AYAs with cancer. NCT05706610.


Asunto(s)
Neoplasias , Adolescente , Humanos , Adulto Joven , Estudios de Factibilidad , Cumplimiento de la Medicación , Neoplasias/tratamiento farmacológico , Proyectos Piloto , Proyectos de Investigación , Ensayos Clínicos Fase II como Asunto
3.
Pediatr Blood Cancer ; 70(11): e30609, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37553297

RESUMEN

BACKGROUND: Cyclin D has been shown to play an essential role in acute lymphoblastic leukemia (ALL) initiation and progression, providing rationale for targeting the CDK4/6-cyclin D complex that regulates cell cycle progression. PROCEDURE: The Children's Oncology Group AINV18P1 phase 1 trial evaluated the CDK4/6 inhibitor, palbociclib, in combination with standard four-drug re-induction chemotherapy in children and young adults with relapsed/refractory B- and T-cell lymphoblastic leukemia (ALL) and lymphoma. Palbociclib (50 mg/m2 /dose) was administered orally once daily for 21 consecutive days, first as a single agent (Days 1-3) and subsequently combined with re-induction chemotherapy. This two-part study was designed to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D), followed by an expansion pharmacokinetic cohort. RESULTS: Twelve heavily pretreated patients enrolled, all of whom were evaluable for toxicity. One dose-limiting hematologic toxicity (DLT) occurred at the starting dose of 50 mg/m2 /dose orally for 21 days. No additional DLTs were observed in the dose determination or pharmacokinetic expansion cohorts, and overall rates of grade 3/4 nonhematologic toxicities were comparable to those observed with the chemotherapy platform alone. Five complete responses were observed, two among four patients with T-ALL and three among seven patients with B-ALL. Pharmacokinetic studies showed similar profiles with both liquid and capsule formulations of palbociclib. CONCLUSIONS: Palbociclib in combination with re-induction chemotherapy was well tolerated with a RP2D of 50 mg/m2 /day for 21 days. Complete responses were observed among heavily pretreated patients.


Asunto(s)
Linfoma de Células B , Linfoma , Leucemia-Linfoma Linfoblástico de Células Precursoras , Niño , Humanos , Adulto Joven , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Linfoma/tratamiento farmacológico , Linfoma de Células B/tratamiento farmacológico , Dosis Máxima Tolerada , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiología
5.
Blood Adv ; 7(13): 3225-3231, 2023 07 11.
Artículo en Inglés | MEDLINE | ID: mdl-36897253

RESUMEN

Outcomes for children and adolescents with relapsed and refractory Hodgkin lymphoma (HL) are poor, with ∼50% of patients experiencing a subsequent relapse. The anti-CD30 antibody-drug conjugate brentuximab vedotin improved progression-free survival (PFS) when used as consolidation after autologous stem cell transplantation (ASCT) in adults with high-risk relapsed/refractory HL. Data on brentuximab vedotin as consolidative therapy after ASCT in pediatric patients with HL are extremely limited, with data of only 11 patients reported in the literature. We performed a retrospective analysis of 67 pediatric patients who received brentuximab vedotin as consolidation therapy after ASCT for the treatment of relapsed/refractory HL to describe the experience of this regimen in the pediatric population. This is the largest cohort reported to date. We found that brentuximab vedotin was well tolerated with a safety profile similar to that of adult patients. With a median follow-up of 37 months, the 3-year PFS was 85%. These data suggest a potential role for the use of brentuximab vedotin as consolidation therapy after ASCT for children with relapsed/refractory HL.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Enfermedad de Hodgkin , Adulto , Adolescente , Humanos , Niño , Brentuximab Vedotina/uso terapéutico , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/patología , Trasplante Autólogo , Estudios Retrospectivos
6.
Transplant Cell Ther ; 29(5): 311.e1-311.e7, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36809824

RESUMEN

Bridging therapy (BT) given during the period between T-cell collection and initiation of lymphodepleting chemotherapy is indicated for most children with B-cell acute lymphoblastic leukemia (B-ALL) undergoing treatment with tisagenlecleucel (tisa-cel), a CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy. Both conventional chemotherapy agents and B-cell directed antibody-based therapies such as antibody-drug conjugates and bispecific T-cell engagers have been used as systemic forms of BT. The purpose of this retrospective study was to evaluate if there are detectable differences in clinical outcomes based on the type of BT given (conventional chemotherapy or inotuzumab). A retrospective analysis was performed on all patients treated with tisa-cel at Cincinnati Children's Hospital Medical Center for B-ALL with bone marrow disease (with or without extramedullary disease). Patients who did not receive systemic BT were excluded. Only 1 patient received blinatumomab as BT and was therefore not included in this analysis to focus the analysis on the use of inotuzumab. Pre-infusion characteristics and post-infusion outcomes were collected. Fisher's exact test was used for categorical variables, and t-test or Mann-Whitney test was used for continuous parametric and non-parametric variables respectively. Mantel-Cox was used for survival analyses. Thirty-two patients received BT before CD19 CAR-T for medullary leukemia; 24 received conventional chemotherapy, and 8 received inotuzumab ozogamicin (InO). Cohorts were evenly matched regarding CAR-T indication, recipient age, and median CAR-T cell dose. There were no significant differences between the groups for attaining a minimal residual disease (MRD)-negative complete response after CAR-T, the percentage of patients who maintained prolonged B-cell aplasia, or the median duration of B-cell aplasia. Thirty-seven percent of patients in the conventional chemotherapy group and 43% in the antibody-based therapy group relapsed, with a median time to relapse in both groups of 5 months. No differences in event-free survival, the cumulative incidence of relapse, or overall survival were seen between the two groups. Initial response to tisa-cel, relapse rate, and survival were similar between patients who received BT with conventional chemotherapy or InO therapy. Because low disease burden at the time of infusion is a positive prognostic factor, choice of bridging regimen should focus on therapy that is anticipated to effectively lower disease burden and minimize treatment-related toxicity. Given the limitations associated with the single center retrospective analysis, a larger, multicenter study is needed to further explore these findings.


Asunto(s)
Leucemia-Linfoma Linfoblástico de Células Precursoras B , Leucemia-Linfoma Linfoblástico de Células Precursoras , Receptores Quiméricos de Antígenos , Humanos , Niño , Inotuzumab Ozogamicina/uso terapéutico , Receptores Quiméricos de Antígenos/uso terapéutico , Estudios Retrospectivos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamiento farmacológico , Recurrencia
7.
Pediatr Blood Cancer ; 70(3): e30186, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36602026

RESUMEN

BACKGROUND: Adherence promotion is a critical component of adolescent and young adult (AYA) cancer care, but predictors of nonadherence that could be targeted in intervention efforts remain largely unknown. The purpose of this multi-site longitudinal observational study was to examine the relationship between barriers and medication adherence among AYAs with cancer. PROCEDURE: Sixty-five AYAs (ages 15-24 years; mean age = 18.97 years, SD = 2.51; Mmean time since diagnosis = 1.42 years, SD = 1.95) with newly diagnosed or relapsed cancer completed self-report measures of barriers and adherence at quarterly study visits and used an electronic adherence monitoring device for 12 months. Longitudinal mixed effects models were used to examine our primary hypothesis that greater barriers are related to lower adherence over time. Descriptive statistics were used to explore our secondary aim of describing the frequency and patterns of barriers endorsed by AYAs with cancer. RESULTS: After controlling for covariates (time, medication type, race, ethnicity, diagnosis, time since diagnosis), a greater number of barriers was associated with lower electronically monitored (ß = -5.99, p = .005) and self-reported (ß = -1.92, p < .001) adherence. The specific barriers endorsed by AYAs differed across participants, and the majority of AYAs endorsed an entirely different pattern of barriers than any other AYA in the study. CONCLUSION: Barriers are associated with nonadherence and may be a promising target for intervention. Individual variability across barriers, however, suggests that tailoring may be necessary, and a promising next step is to explore personalized approaches to adherence promotion.


Asunto(s)
Neoplasias , Humanos , Adolescente , Adulto Joven , Adulto , Neoplasias/tratamiento farmacológico , Autoinforme , Estudios Longitudinales , Enfermedad Crónica , Cumplimiento de la Medicación
8.
Blood Adv ; 7(4): 602-610, 2023 02 28.
Artículo en Inglés | MEDLINE | ID: mdl-36541957

RESUMEN

Part 1 results of the open-label, randomized, global phase 3 SPARKLE trial supported continued assessment of ibrutinib with either modified rituximab, ifosfamide, carboplatin, and etoposide (RICE) or rituximab, vincristine, ifosfamide, carboplatin, idarubicin, and dexamethasone (RVICI) in pediatric patients with relapsed/refractory (R/R) mature B-cell non-Hodgkin lymphoma (B-NHL). We report final results of Part 2 evaluating the efficacy of ibrutinib plus RICE or RVICI vs RICE/RVICI alone. Patients aged 1 to 30 years (initial diagnosis <18 years) were randomized 2:1 to receive ibrutinib with or without RICE/RVICI. Primary endpoint was event-free survival (EFS) based on independent committee-confirmed events. Fifty-one patients were enrolled. Median age was 15 years; Burkitt lymphoma, Burkitt leukemia, and Burkitt-like lymphoma (total: 45%) and diffuse large B-cell lymphoma/primary mediastinal B-cell lymphoma (51%) were the most common subtypes. At the preplanned interim analysis, median EFS was 6.1 vs 7.0 months with ibrutinib plus RICE/RVICI vs RICE/RVICI, respectively (hazard ratio, 0.9; 90% confidence interval, 0.5-1.6; P = .387); further enrollment was ceased. With ibrutinib plus RICE/RVICI vs RICE/RVICI, median overall survival was 14.1 vs 11.1 months, overall response rate was 69% vs 81%, and 46% vs 44% proceeded to stem cell transplantation. In both treatment arms, 100% of patients experienced grade ≥3 treatment-emergent adverse events. No EFS benefit was seen with ibrutinib. Salvage was generally poor in patients who received prior rituximab, regardless of treatment arm. No new safety signals were observed. Ibrutinib exposure in pediatric patients fell within the target range of exposure in adults. Trial is registered on www.clinicaltrials.gov (NCT02703272).


Asunto(s)
Ifosfamida , Linfoma de Células B Grandes Difuso , Humanos , Adulto Joven , Niño , Adolescente , Rituximab , Etopósido , Carboplatino
9.
J Adolesc Young Adult Oncol ; 11(6): 605-610, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35049383

RESUMEN

This study described inpatient physical therapy (PT) adherence and barriers to inpatient PT among adolescents and young adults (AYAs) with hematologic malignancies receiving care at a Midwestern children's hospital. Forty-seven AYAs receiving care over a 2-year period were included. PT contact was established in 93% of hospitalizations. AYAs declined an average of 34% of PT visits, resulting in PT visits on 27% of hospitalized days, 1 day less than the goal of 3 days a week. The most frequent reasons for decline included: AYA sleeping (22%), AYA undergoing medical procedure (18%), and AYA not feeling well (12%).


Asunto(s)
Neoplasias Hematológicas , Niño , Humanos , Adolescente , Modalidades de Fisioterapia , Neoplasias Hematológicas/terapia
10.
Pediatr Blood Cancer ; 68(8): e29126, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34019326

RESUMEN

No guidelines exist for which intensive chemotherapy regimen is best in pediatric or young adult patients with high-risk posttransplant lymphoproliferative disorder (PTLD). We retrospectively reviewed patients with PTLD who received interval-compressed short-course etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (SC-EPOCH) regimens at our institution. Eight patients were included with median age of 12 years. All patients achieved a complete response with a manageable toxicity profile. Two patients developed second, clonally unrelated, EBV-positive PTLD and one patient had recurrence at 6 months off therapy. No graft rejection occurred during therapy. All eight patients are alive with median follow-up of 29 months.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trastornos Linfoproliferativos , Trasplante de Órganos/efectos adversos , Niño , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Etopósido/uso terapéutico , Humanos , Trastornos Linfoproliferativos/tratamiento farmacológico , Trastornos Linfoproliferativos/etiología , Complicaciones Posoperatorias , Prednisona/uso terapéutico , Pronóstico , Estudios Retrospectivos , Vincristina/uso terapéutico , Adulto Joven
11.
Cancer Discov ; 11(6): 1440-1453, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33593877

RESUMEN

Combining venetoclax, a selective BCL2 inhibitor, with low-dose navitoclax, a BCL-XL/BCL2 inhibitor, may allow targeting of both BCL2 and BCL-XL without dose-limiting thrombocytopenia associated with navitoclax monotherapy. The safety and preliminary efficacy of venetoclax with low-dose navitoclax and chemotherapy was assessed in this phase I dose-escalation study (NCT03181126) in pediatric and adult patients with relapsed/refractory (R/R) acute lymphoblastic leukemia or lymphoblastic lymphoma. Forty-seven patients received treatment. A recommended phase II dose of 50 mg navitoclax for adults and 25 mg for patients <45 kg with 400 mg adult-equivalent venetoclax was identified. Delayed hematopoietic recovery was the primary safety finding. The complete remission rate was 60%, including responses in patients who had previously received hematopoietic cell transplantation or immunotherapy. Thirteen patients (28%) proceeded to transplantation or CAR T-cell therapy on study. Venetoclax with navitoclax and chemotherapy was well tolerated and had promising efficacy in this heavily pretreated patient population. SIGNIFICANCE: In this phase I study, venetoclax with low-dose navitoclax and chemotherapy was well tolerated and had promising efficacy in patients with relapsed/refractory acute lymphoblastic leukemia or lymphoblastic lymphoma. Responses were observed in patients across histologic and genomic subtypes and in those who failed available therapies including stem cell transplant.See related commentary by Larkin and Byrd, p. 1324.This article is highlighted in the In This Issue feature, p. 1307.


Asunto(s)
Compuestos de Anilina/uso terapéutico , Antineoplásicos/uso terapéutico , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Sulfonamidas/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Compuestos de Anilina/administración & dosificación , Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica , Compuestos Bicíclicos Heterocíclicos con Puentes/administración & dosificación , Niño , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Inducción de Remisión , Sulfonamidas/administración & dosificación , Resultado del Tratamiento , Adulto Joven
12.
J Adolesc Young Adult Oncol ; 10(3): 351-354, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33085558

RESUMEN

There is a critical need to engage adolescents and young adults (AYAs) with cancer in conversations regarding "safer" sexual activity during treatment. Many providers, however, report lacking the knowledge and/or tools to engage in these discussions. This article describes the experience of one pediatric institution in assessing and addressing provider barriers to safer sexual activity discussions among AYAs with cancer. Feedback from patients and providers resulted in an educational handout detailing recommendations regarding safer sex practices for AYAs with cancer. Handout adoption, acceptability, appropriateness, and feasibility are described alongside barriers to assist other institutions seeking to develop similar interventions.


Asunto(s)
Neoplasias , Sexo Seguro , Adolescente , Niño , Comunicación , Humanos , Neoplasias/terapia , Adulto Joven
14.
J Adolesc Young Adult Oncol ; 8(4): 417-422, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31013460

RESUMEN

Background: Location of death (LOD) is an important aspect of end-of-life (EOL) care. Adolescents and young adults (YAs) with pediatric malignancies are increasingly treated in pediatric institutions. YAs, generally defined as 18-39 years old, deserve specific attention because adults have unique developmental and social considerations compared with younger patients. Objective: The goal of this retrospective cohort study was to understand the effect of treatment by a pediatric oncology program on EOL experiences for YAs. Specifically, we examined LOD, hospice, and palliative care (PC) involvement in a cohort of YAs who died of cancer in a large, quaternary care pediatric hospital. Methods: This was a retrospective cohort study of patients ≥18 years of age, who died of cancer between January 1, 2010, and December 31, 2017. Standardized data were abstracted from the institutional cancer registry and the electronic medical record. Results: YAs in this cohort more commonly died in the hospital (54.9%). Lack of hospice involvement and the presence of a documented do-not-resuscitate (DNR) order were significantly associated with inpatient death. The majority of patients had long-standing PC involvement (95.8%, median 318 days), a DNR order (78.9%), and had enrolled in hospice care (60.6%) before death. Conclusions: These results suggest that a significant proportion of YAs with cancer remain inpatient for EOL care. Pediatric oncologists and PC teams may benefit from additional training in the unique psychosocial needs of YAs to optimize EOL care for these older patients.


Asunto(s)
Conducta de Elección , Cuidados Paliativos al Final de la Vida/estadística & datos numéricos , Hospitales Pediátricos/estadística & datos numéricos , Neoplasias/mortalidad , Neoplasias/terapia , Cuidado Terminal/estadística & datos numéricos , Adolescente , Adulto , Femenino , Estudios de Seguimiento , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/psicología , Cuidados Paliativos/estadística & datos numéricos , Pronóstico , Estudios Retrospectivos , Adulto Joven
15.
J Adolesc Young Adult Oncol ; 7(4): 499-503, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29634391

RESUMEN

There is a growing interest by both pediatric and medical oncologists to develop adolescent and young adult (AYA)-specific cancer programs. Input from AYA patients is critical to the successful design of these programs and to ensuring that patient needs are met. As traditional in-person advisory groups may not be the most appropriate means for engaging AYAs, this article describes the creation and implementation of a novel, developmentally appropriate, and efficient Young Adult Advisory Program. Reach, uptake, and participant demographic and clinical characteristics are presented alongside lessons learned. The findings are offered to assist others seeking to engage AYAs in program development and quality improvement efforts.


Asunto(s)
Comités Consultivos/normas , Neoplasias/terapia , Participación del Paciente/métodos , Femenino , Humanos , Masculino , Neoplasias/patología
16.
Pediatr Blood Cancer ; 65(5): e26944, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29292843

RESUMEN

BACKGROUND: Ontuxizumab is a humanized IgG monoclonal antibody that targets the cell-surface glycoprotein endosialin (tumor endothelial marker-1[TEM-1]/CD248) found on activated mesenchymal cells and certain tumors. Ontuxizumab binding to endosialin may interfere with platelet-derived growth factor signaling, prevent tumor stroma organization, and prevent new vessel formation. METHODS: Ontuxizumab was administered intravenously on days 1, 8, 15, and 22 of a 28-day cycle at three dose levels (4, 8, and 12 mg/kg). Further dose escalation to 16 mg/kg was planned if the maximum tolerated dose (MTD) was not reached and the ontuxizumab systemic clearance was ≥30% higher in children compared to adults. Following determination of the MTD/recommended phase 2 dose, an additional cohort of six patients (<12 years) was enrolled for further pharmacokinetics (PK) evaluation. RESULTS: Twenty-seven eligible patients (17 male, median age 15 years, range 3-21 years) were enrolled. Twenty-two patients (neuroblastoma [5], Ewing sarcoma [4], rhabdomyosarcoma [4], and other tumors [9]) were fully evaluable for toxicity. Five patients did not complete cycle 1 due to tumor progression. Two of 10 patients experienced dose-limiting toxicity of bacteremia (n = 1) and hyponatremia (n = 1) at 12 mg/kg. Grade ≤2 fever or infusion-related reactions occurred in 10 patients. Clearance was dose dependent and within 30% of adult value at 12 mg/kg. CONCLUSION: Ontuxizumab administered weekly at 12 mg/kg appears to be well tolerated in children with relapsed or refractory solid tumors. The PK of ontuxizumab does not appear to be significantly different in children compared to adults.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Resistencia a Antineoplásicos/efectos de los fármacos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Terapia Recuperativa , Adolescente , Adulto , Niño , Preescolar , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Dosis Máxima Tolerada , Recurrencia Local de Neoplasia/patología , Neoplasias/patología , Pronóstico , Tasa de Supervivencia , Adulto Joven
17.
Invest New Drugs ; 35(1): 108-114, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-27718038

RESUMEN

Importance Use of expansion cohorts (EC) in phase I trials is increasing. However, the utility of phase I EC in aiding drug development is unclear. We sought to determine factors associated with the inclusion of EC in phase I studies and the impact of EC on subsequent clinical development. Methods We performed a systematic review of all phase I trials published in the Journal of Clinical Oncology between June 2004 and May 2014. Presence of an EC, number of participants, funding source, class of agent, tumor type, and maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) were identified. Subsequent conduct of phase II studies and FDA approval of the study agent was also assessed. Results We identified 252 phase I studies. An EC was included in 105 studies. Average accrual on EC studies was 47 compared to 31 in studies without EC (p < 0.0001). There was no impact of time on the inclusion of EC. Only 4 % of phase I studies with an EC provided sample size justification. Source of funding had the only significant association with inclusion of EC. Addition of a phase I EC did not impact the phase I MTD/RP2D, subsequent phase II trial, or FDA approval. Conclusion The importance of including an EC in phase I trials is subject to ongoing debate. Our results demonstrated little benefit to including EC in phase I studies. These findings support that innovative design strategies are needed to optimize the utility of EC in phase I studies.


Asunto(s)
Antineoplásicos , Ensayos Clínicos Fase I como Asunto/métodos , Proyectos de Investigación , Humanos , Oncología Médica/métodos
18.
Br J Clin Pharmacol ; 82(3): 728-38, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27121262

RESUMEN

AIM: The aim of the present study was to characterize the pharmacokinetics of the oral proteasome inhibitor, ixazomib, in patients with solid tumours and moderate or severe hepatic impairment, to provide posology recommendations. METHODS: Eligible adults with advanced malignancies for which no further effective therapy was available received a single dose of ixazomib on day 1 of the pharmacokinetic cycle; patients with normal hepatic function, moderate hepatic impairment or severe hepatic impairment received 4 mg, 2.3 mg or 1.5 mg, respectively. Blood samples for single-dose pharmacokinetic characterization were collected over 336 h postdose. After sampling, patients could continue to receive ixazomib on days 1, 8 and 15 in 28-day cycles. RESULTS: Of 48 enrolled patients (13, 15 and 20 in the normal, moderate and severe groups, respectively), 43 were pharmacokinetics-evaluable. Ixazomib was rapidly absorbed (median time to reach peak concentration was 0.95-1.5 h) and highly bound to plasma proteins, with a similar mean fraction bound (~99%) across the three groups. In patients with moderate/severe hepatic impairment (combined group), the geometric least squares mean ratios (90% confidence interval) for unbound and total dose-normalized area under the plasma concentration vs. time curve from time zero to the time of the last quantifiable concentration in reference to the normal hepatic function group were 1.27 (0.75, 2.16) and 1.20 (0.79, 1.82), respectively. Seven (15%) of the 48 patients experienced a grade 3 drug-related adverse event; there were no drug-related grade 4 adverse events. CONCLUSIONS: In patients with moderate/severe hepatic impairment, unbound and total systemic exposures of ixazomib were 27% and 20% higher, respectively, vs. normal hepatic function. A reduced ixazomib starting dose of 3 mg is recommended for patients with moderate or severe hepatic impairment.


Asunto(s)
Compuestos de Boro/farmacocinética , Glicina/análogos & derivados , Hepatopatías/sangre , Neoplasias/sangre , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Compuestos de Boro/administración & dosificación , Compuestos de Boro/sangre , Femenino , Glicina/administración & dosificación , Glicina/sangre , Glicina/farmacocinética , Humanos , Hepatopatías/complicaciones , Hepatopatías/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Inhibidores de Proteasoma/administración & dosificación , Inhibidores de Proteasoma/sangre , Inhibidores de Proteasoma/farmacocinética , Adulto Joven
19.
Pediatr Dermatol ; 32(3): e95-7, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25690855

RESUMEN

A blue patch on the vertex scalp of an infant has a broad differential diagnosis, including vascular malformations, melanocytic lesions, trauma, and exogenous or endogenous pigmentation. We present two cases of infants who developed blue patches on the scalp. Extensive examination including MRI and biopsy was recommended for one of the patients to further characterize the lesion and its possible medical implications. In both, the blue discoloration had been due to repetitive contact with the sticker on a tub of baby wipes that had rubbed off onto the scalp. We present these infants to highlight this exogenous and benign cause of blue pigmentation and help practitioners avoid unnecessary examination.


Asunto(s)
Colorantes , Cuero Cabelludo , Diagnóstico Diferencial , Femenino , Humanos , Lactante , Masculino
20.
Lancet ; 384(9954): 1574, 2014 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-25443486
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