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EAPH-03. FINAL RESULTS OF THE PHASE II, SINGLE ARM TRIAL OF IRINOTECAN AND CISPLATIN IN CHILDREN WITH HIGH-RISK GLIAL TUMORS

ABSTRACT: Abstract We conducted an open label, single arm phase II clinical trial with with irinotecan and cisplatin (I/C) for pediatric patients with glial tumors (EudraCT:2009-010742-59). METHODS Patients diagnosed with high-risk (HR) gliomas at diagnosis (HGG, ependymomas, DIPG, or HR-LGG) received sixteen weekly outpatient iv. cycles of Cisplatin(30mg/m2) and Irinotecan(65mg/m2). Malignant gliomas received radiation at progression. Objective response was assessed with MRI plus volumetric analysis. Clinical and neurological changes were assessed. RESULTS Since November/2009 until December/2012, 39 patients (66,7% females), aged 7m-17y (mean=84-months), diagnosed with DIPG(n=7), HGG(n=5), anaplastic-ependymoma(n=6), atypical neurocytoma(n=1), LGG n=20: Pilocytic Astrocytoma(n=7), Pilomyxoid A.(n=1), Astrocytoma NOS(n=5), Grade-II astrocytoma (n=2), Ganglioglioma(n=2), LGG-NF1(n=3) were included. Most frequent events were nausea/vomiting, mostly grade 1–2, only 5/39 grade >2; 17 patients (43,6%) developed grade-1 diarrhea. At the end of follow-up 3/31 patients developed hypoacusia, all grade 1 (9,7%). Five (45.5%) patients with HGG, 1 relapsed HGG(100%), 7 DIPG(100%) and 3 LGG(15.0%) progressed during treatment, ending prematurely the study. Objective response rate (ORR) at the end of therapy (week 21), was by ITT / PP, of 54,4% for HGG, 0% for DIPG, and 85% for HR-LGG After a median follow-up time of 67.5 months, OS/EFS was 0/0% for relapsed HGG and DIPG, 62%/23% for High-grade glial tumors, and 95%/43% for HR-LGG. Radiation was avoided in 19/20 HR-LGG patients. CONCLUSION The I/C regimen was acceptably tolerated and shows activity for some children with HR-gliomas, mainly HR-LGG.

SUBMITTER: Cruz O

PROVIDER: S-EPMC6012024 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Project description:BackgroundSouthwest Oncology Group 0124 was a large North American phase 3 trial that failed to confirm a survival benefit for cisplatin/irinotecan over cisplatin/etoposide in patients with extensive stage small cell lung cancer (SCLC). These results were contrary to Japan Clinical Oncology Group 9511, a phase 3 trial exclusively in Japanese patients. Because 0124 and 9511 used identical treatment regimens and similar eligibility criteria, patient-level data were pooled from both trials, and a common arm analysis was performed to explore potential reasons for the divergent results.MethodsPatients with documented extensive stage SCLC and adequate end-organ function were randomized to intravenously receive either cisplatin 60 mg/m(2) Day 1 + irinotecan 60 mg/m(2) Days 1, 8, and 15 every 4 weeks or cisplatin 80 mg/m(2) Day 1 + etoposide 100 mg/m(2) Days 1-3 every 3 weeks. Demographic and outcome data were compared among 805 patients enrolled in 9511 and 0124 receiving identical treatment using a logistic model adjusted for age, sex, and performance status (PS).ResultsOf 671 patients in 0124, 651 eligible patients were included, as were all 154 patients from 9511. Significant differences in sex and PS distribution as well as toxicity were seen between trials. There were also significant differences in response rates (87% vs 60%, P<.001) and median overall survival (12.8 vs 9.8 months, P<.001) when the cisplatin/irinotecan arms from both trials were compared.ConclusionsSignificant differences in patient demographics, toxicity, and efficacy were identified in the 9511 and 0124 populations. These results, relevant in the current era of clinical trials globalization, warrant: 1) consideration of differential patient characteristics and outcomes among populations receiving identical therapy; 2) utilization of the common arm model in prospective trials; and 3) inclusion of pharmacogenomic correlates in cancer trials where ethnic/racial differences in drug disposition are expected.

Project description:BackgroudThe European Organization for Research and Treatment of Cancer (EORTC) trial 22,911 reported 74% 5-year biochemical disease-free survival (bDFS) in patients with prostate carcinoma treated with radical prostatectomy (RP) followed by postoperative radiotherapy (RT). This study aimed to improve these outcomes by using a combined-intensified-modulated-adjuvant treatment, including RT and hormone therapy (HT) after RP.Materials and methodsThis phase I/II trial treatment was designed to improve 5-year bDFS from ~ 75 to 90%. Patients were consecutively enrolled using the following inclusion criteria: age < 80 years, histological diagnosis of prostate adenocarcinoma without known metastases, stage pT2-4N0-1, and Eastern Cooperative Oncology Group performance status of 0-2. All patients had at least one of these pathologic features: capsular perforation, positive surgical margins, seminal vesicle invasion, and pelvic lymph nodes involvement. A minimum dose of 64.8 Gy to the tumor bed was delivered in all patients. Depending on tumor characteristics at diagnosis, patients received a higher dose (70.2 Gy; 85.4%) and/or prophylactic pelvic lymph nodes irradiation (57.7%) and/or HT (69.1%). Biochemical relapse was defined as two consecutive rising prostate-specific antigen (PSA) values > 0.2 ng/ml.ResultsA total of 123 patients were enrolled in the study and completed the scheduled treatment. Median preoperative and postoperative PSA were: 8.8 and 0.06 ng/mL, respectively. The percentages of patients with pathologically involved nodes and positive resection margins were: 14.6% and 58.5%, respectively. With a median follow-up of 67 months (range: 37-120 months), the actuarial 5-year bDFS, local control, metastasis-free survival, and overall survival (OS) were: 92.9%, 98.7%, 96.1%, and 95.1%, respectively.ConclusionA higher 5-year bDFS (92.9%) was recorded compared to studies based on standard adjuvant RT, even though patients with nodal disease and detectable postoperative PSA were enrolled. Clinical end points, as long-term disease-free survival and OS, will require further assessments. (ClinicalTrials.gov: NCT03169933).

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EAPH-03. FINAL RESULTS OF THE PHASE II, SINGLE ARM TRIAL OF IRINOTECAN AND CISPLATIN IN CHILDREN WITH HIGH-RISK GLIAL TUMORS

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