Efficacy of protracted dose-dense temozolomide (TMZ) in patients with progressive high-grade glioma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e13018-e13018
Author(s):  
M. U. Abacioglu ◽  
H. B. Caglar ◽  
P. F. Yumuk ◽  
Z. Akgun ◽  
B. M. Atasoy ◽  
...  
Keyword(s):  
Study Drug ◽  
High Grade Glioma ◽  
Median Number ◽  
High Grade ◽  
Female Ratio ◽  
Best Response ◽  
Group 2 ◽  
Grade 3 ◽  
Dose Dense ◽  
Group 1

e13018 Background: The study was aimed to evaluate the efficacy of TMZ on a protracted dose-dense schedule after standard 5-day TMZ regimen in patients with progressive high-grade glioma. Methods: In this phase II prospective study, patients who had progression on standard 5-day TMZ for recurrence (group 1) or recurrence after concurrent radiotherapy+TMZ and ≥ 2 cycles of adjuvant TMZ (group 2) for high-grade glioma received TMZ 100 mg/m2× 21 q28 days until progression according to MacDonald's criteria. Patients were included in the study after ethical committee approval and written informed consent. The primary end-point was 6 months PFS. Secondary end-points were OS and toxicity. Results: Between October 2006 and October 2008, 25 patients were included in the study. Nine of the patients were group 1 and 16 of them were group 2. Male/female ratio was 18/7. The median age was 50 (range, 18–70) and median KPS score was 80 (range, 50–100). The histopathology was glioblastoma in 18 and grade 3 glioma (anaplastic astrocytoma, anaplastic oligoastrocytoma or anaplastic oligodendroglioma) in 7. The median cycles of 5-day TMZ received before study entry was 6 (range, 2–18) in group 1 and 6 (2–7) in group 2. With a median follow up of 6 months (1–14 months) the median number of 21-day TMZ cycles received was 2 (range, 1–8). Radiological evaluation could not be performed in 5 patients because of early clinical progression. The best response during treatment was partial response in 2 (8%), stable disease in 9 (36%), and progression in 9 (36%) out of 20 patients assessed. The median time to progression was 2 months (1–8 months) and 6 months PFS rate was 11%. The median OS time was 8 months and 1 year OS rate was 38%. Out of 80 cycles received there was no anemia; 5 (6%) grade 1, 8 (10%) grade 2, 2 (3%) grade 3 leucopenia; 1 (1%) grade 1, 2 (3%) grade 2, 1 (1%) grade 3, 1 (1%) grade 4 thrombocytopenia; 9 (11%) grade 1, 7 (9%) grade 2, 32 (40%) grade 3, and 11 (14%) grade 4 lymphopenia. Study was terminated in 2 patients (one with grade 4 thrombocytopenia and the other with grade 4 hepatic toxicity). There was no dose reduction in the study drug due to toxicity. Conclusions: Protracted dose-dense TMZ after 5-day schedule for recurrent or progressive disease has modest efficacy with tolerable toxicity. No significant financial relationships to disclose.

Cognitive functioning in long-term survivors of high-grade glioma

1994 ◽  
Vol 80 (2) ◽  
pp. 247-253 ◽  
Author(s):  
Yvonne M. Archibald ◽  
Diane Lunn ◽  
Lesley A. Ruttan ◽  
David R. Macdonald ◽  
Rolando F. Del Maestro ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
High Grade Glioma ◽  
High Grade ◽  
Content Type ◽  
Group 2 ◽  
Long Term Survivors ◽  
Disease Free ◽  
Fine Print ◽  
Group 1

✓ In a pilot study, two groups of patients with malignant glioma underwent sequential neuropsychological evaluations after successful tumor treatment. Group 1 included nine patients treated from 1981 to 1985; all patients received irradiation and eight underwent chemotherapy. The baseline neuropsychological assessment was performed 1 to 63 months after tumor diagnosis, with follow-up evaluations at irregular intervals over the next 3 to 7 years. Six patients in Group 1 exhibited impairment on most measures at baseline; subsequently, two patients developed profound cognitive impairment. Initially, three patients functioned in the average range on most tasks; thereafter, two deteriorated on one measure each. Group 2 was ascertained prospectively and included 16 patients treated from 1985 to 1987, all of whom received irradiation and chemotherapy. The first evaluation was performed 18 months after diagnosis, then every 6 months for 2 years, and then yearly. Compared to a control group, those in Group 2 had significant cognitive impairment at baseline. Cognitive performance did not change over the next 12 months in 10 patients who remained free of tumor, but within 2 years of baseline testing, deterioration on specific tasks was evident in two of seven disease-free survivors. When last tested, five of six disease-free survivors had deteriorated on one or more measures. Unlike Group 1, severe global cognitive impairment was not seen, perhaps because Group 2 was followed for a shorter time. Verbal and nonverbal composite scores derived from intelligence quotient (IQ) tests showed less impairment at baseline than did other measures and were more likely to remain stable subsequently. Verbal memory and sustained attention were the most impaired at baseline, and verbal learning and flexibility in thinking showed the greatest tendency to decline over time. Cognitive functioning in survivors of high-grade glioma is best measured and monitored by tests that probe a broader spectrum of abilities than IQ. Neuropsychological measures used in this analysis lacked sensitivity at the lower end of the impaired range. Future studies should use tests better able to discern cognitive differences at low performance levels. Based on this experience, the authors conclude that most long-term survivors of high-grade glioma will have significant cognitive difficulties, usually evident by the first assessment; some patients will develop profound impairment years later, and few are capable of fully independent living.

Pattern Recognition to Prognosticate Endometrial Cancer: The Science Behind the Art of Office Hysteroscopy—A Retrospective Study

2016 ◽  
Vol 26 (4) ◽  
pp. 705-710 ◽  
Author(s):  
Hsuan Su ◽  
Deeksha Pandey ◽  
Ling-Yu Liu ◽  
Chih-Feng Yen ◽  
Chin-Jung Wang ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Invasive Disease ◽  
Type I ◽  
High Grade ◽  
Office Hysteroscopy ◽  
Group 2 ◽  
Grade 3 ◽  
Pattern Group ◽  
Histopathological Grading ◽  
Group 1

ObjectiveThis study aimed to evaluate a specific glomerular pattern for prognostication of endometrial cancer (EC).Materials and MethodsThe office hysteroscopy’s picture and video of 4197 women were reviewed, 48 women who were suspected of type I EC were analyzed: 26 have glomerular pattern (group 1) and 22 without it (group 2).ResultsThe histopathological grading after hysterectomy with glomerular pattern had grade 2 or grade 3 disease on final histology (n = 25; 96%). The sensitivity and specificity of this test were 84.6% and 81.8%, respectively, with a likelihood ratio of 4:6 in predicting and prognosticating those women who have high-grade tumor or invasive disease.ConclusionsThis hysteroscopic picture might be used as a novel marker for risk stratification of EC.

Use of Lenalidomide (Revlimid® +/− Corticosteroids in Relapsed/Refractory Multiple Myeloma Patients with Elevated Baseline Serum Creatinine Levels.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3548-3548 ◽  
Author(s):  
Donna E. Reece ◽  
Esther Masih-Khan ◽  
Christine Chen ◽  
Lisa Wang ◽  
Saima Dean ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Platelet Count ◽  
Serum Creatinine ◽  
Median Number ◽  
Bleeding Complications ◽  
Baseline Serum ◽  
Prior Therapy ◽  
Group 2 ◽  
Grade 3 ◽  
Group 1

Abstract Lenalidomide (Revlimid®; Rev) is an important novel agent for the treatment of multiple myeloma (MM) patients (pts). Since MM pts are at risk for renal insufficiency, we evaluated whether an abnormal serum creatinine (cr) level affected the outcome of pts treated with Rev +/− corticosteroids (CS). Between 12/05 and 07/06, 69 MM pts who had progressed after at least 1 line of prior therapy were treated in our center with Rev +/− CS as part of Celgene’s Expanded Access Program in Canada. Eligibility criteria included a platelet count (pl ct) ≥ 30 x 109/L and neutrophil count ≥ 1.0 x 109/L; a cr level of ≤220 umol/L was required unless a waiver was obtained. Protocol therapy consisted of Rev + dexamethasone (dex) in 44, Rev + prednisone in 7, Rev + dex and prednisone at different time points in 5 and Rev alone in 13. The median age was 60 yrs (35–79); 36 (52%) were male; median β2-microglobulin was 214 nm/L (114–1420); Ig subtype was IgG in 42, IgA in 12, IgM in 1 and light chain only in 14. Prior therapy included ASCT in 59 pts (86%), thalidomide in 51 (74%), bortezomib in 21 (30%) and oral cyclophosphamide in 52 (75%); the median number of prior regimens was 2 (1–5). Twenty-three pts (33%) had an elevated baseline cr level (> 89 umol/L for females and 109 umol/L for males in our center). The median cr was 138 umol/L (110–412) in these pts (group 1), compared with 80 umol/L (51–109) in group 2 (control) (p=0.001). Five pts in group 1 had a cr level ≥ 177 umol/L (2 mg/dL). Both groups were similar except that group 1 had more males (p=0.04) and the baseline platelet count (pl ct) was lower (35% vs. 4% with pl ct less than 50 x 109/L; p=0.0007). RESULTS: The median number of cycles of Rev +/− CS given to date was 4 (1–8) in both groups, and the median follow-up is 4 mos (0.5–8). After 3 cycles of Rev, the median cr was 104 umol/L (61–372) in group 1 and 79 umol/L (53–180) in group 2. In group1, cr decreased in 39% and increased in 26%, compared with 39% and 32% in group 2, respectively (p=0.56). The incidence of grade 3–4 neutropenia was 43% vs. 46%, febrile neutropenia 13% vs. 9%, any infection 17% vs. 20% and G-CSF use 66% vs. 57% among pts in group 1 vs. 2 (p=NS for all comparisons). More in group 1 experienced grade 3–4 thrombocytopenia and required at least 1 pl transfusion (52% vs. 17%; p=0.003). In group 1, 6 (26%) pts required pl transfusion in only 1 cycle, 5 (22%) in 2 cycles and 1 (4%) in 3 cycles. However, the only 2 significant bleeding complications were seen in group 2. There were 2 deaths (8.7%) in group 1 and 4 (8.7%) in group 2. Table 1 summarizes the preliminary anti-myeloma results in these 2 groups. CONCLUSIONS: Rev +/− CS can be given safely to selected patients with an elevated baseline cr level; pts with an elevated cr had lower baseline pl cts, and required more pl transfusions; the response rate, PFS and OS to date are similar in patients with a normal vs. elevated cr level. Table 1 Serum cr N nCR/PR PFS 95% CI OS 95% CI PFS=progression free survival; OS=overall survival; the differences are not significant. Elevated 23 61% 30% 11–52% 72% 46–86% Normal 46 54% 50% 31–67% 76% 55–88%

Sequential (ST) versus combination (CT) chemotherapy in older patients (pts) with advanced colorectal cancer (aCRC): A retrospective analysis of the CAIRO study

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9542-9542
Author(s):  
J. Doornebal ◽  
A. Wymenga ◽  
N. Antonini ◽  
W. T. van der Graaf ◽  
M. Koopman ◽  
...  
Keyword(s):  
Age Groups ◽  
Progression Free Survival ◽  
Median Number ◽  
Phase Iii ◽  
Appetite Loss ◽  
Comparable Group ◽  
Group 2 ◽  
Grade 3 ◽  
Eortc Qlq ◽  
Group 1

9542 Background: Although older pts have been underrepresented in clinical trials, studies support the efficacy of chemotherapy in older pts with aCRC. We retrospectively evaluated efficacy, tolerability, and quality of life (QoL, EORTC QLQ C30) of older (group 1: ≥ 70 yrs) vs younger pts (group 2: < 70 yrs) who participated in a randomized phase III trial of ST vs CT in CRC (Koopman et al, Lancet 2007). Moreover, differences between ST vs CT were analyzed in both age groups. Methods: All 803 eligible pts were randomized between ST - 1st line capecitabine (Ca) 1250 mg/m2 bid d1–14 (group 1: n = 104/group 2: n = 297), 2nd line irinotecan (Ir) 350 mg/m2 d1 (1:63/2:189) and 3rd line Ca 1000 mg/m2 bid d1–14 + oxaliplatin 130 mg/m2 d1 ([CAPOX], 1:34/2:119) - and CT - 1stline Ca 1000 mg/m2 bid d1–14 + Ir 250 mg/m2 d1 (1:95/2:307), 2nd line CAPOX (1:33/2:165). Cycles were given q 3 weeks. Results: Baseline characteristics, median number of administered cycles and median relative dose intensities were comparable. Group 1 vs 2: Overall survival (OS) and progression free survival (PFS) were comparable (OS: ST: 17.6 vs 16.0 months, HR 1.127 [0.883 - 1.437], CT: 19.8 vs 16.8 months, HR 0.913 [0.708 - 1.178]). A better RR was observed in 1st line ST for group 1 (30% vs 17%). Grade 3–4 toxicity was more common in 1st and 2nd line ST in group 1 (overall grade 3–4 toxicity 54/59% vs 40/43%). However, significant decreases in overall QoL, fatigue, appetite loss, and diarrhea were only reported in CT for group 1. ST vs CT: OS was comparable (1: 17.6 vs 19.8 months; 2: 16.0 vs 16.8 months). A better RR (17% vs 40%) and longer PFS (5.4 vs 7.8 months) were only observed in CT for group 2. Cumulative overall toxicity over all subsequent lines of treatment was worse for ST in group 1 (85% vs 69%). However, significant decreases in overall QoL, symptomatic appetite loss, nausea and vomiting and diarrhea were only reported in group 1 for CT. Conclusions: Older pts derived comparable benefit from both chemotherapeutic strategies compared to younger pts. CT did not result in any benefit in terms of efficacy in older pts. Despite the higher incidence of grade 3–4 toxicities, both efficacy and QoL results support the preference of ST in fit older aCRC patients. No significant financial relationships to disclose.

scholarly journals CTIM-06. DENDRITIC CELL VACCINE STUDY FOR RECURRENT, HIGH-GRADE GLIOMA: TISSUE-BASED RNA SEQUENCING AND SERUM CYTOKINE LEVELS AS POTENTIAL BIOMARKERS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii33-ii34
Author(s):  
Macarena De La Fuente ◽  
Tulay Koru-Sengul ◽  
Deborah Heros ◽  
Feng Miao ◽  
Alain Fernandez Marrero ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Rna Sequencing ◽  
Tumor Antigens ◽  
High Grade Glioma ◽  
Treatment Discontinuation ◽  
Sequencing Analysis ◽  
High Grade ◽  
Who Grade ◽  
Cytokine Levels ◽  
Grade 3

Abstract BACKGROUND Glioblastoma is the most common primary malignant brain tumor. Despite multimodality treatment approach, median progression-free survival (PFS) is only 8 months, median overall-survival (OS) 14 months and 5-year survival rate of under 10%. Dendritic cells (DCs) are the professional antigen presenting cells of the immune system. The rationale for sensitizing dendritic cells to a pool of non-selected tumor antigens is based on the marked heterogeneity present within glioblastoma tumor cells. METHODS Phase 1/feasibility study of DC vaccine for recurrent high-grade glioma was conducted. Pooled, non-selected tumor antigens collected via tumor cell lysate were used for DC sensitization. RNA sequencing analysis was performed on all tumor samples. Cytokine levels in serum were detected using a Luminex cytokine panel. RESULTS A total of 20 patients were enrolled onto this study (median age 58yrs, range: 39–74, 65% male). Pathology showed WHO grade IV glioblastoma in 14 (70%) and grade III anaplastic astrocytoma in 6 (30%) patients. IDH wild type in 19 (95%) patients. Treatment emergent adverse events (all grades, regardless of attribution) occurred in more than 15% of the patients (20% fatigue, 15% dizziness, 15% headache, none leading to treatment discontinuation). There were five grade 3–4 and none grade 5 events. One grade 4 event (seizure) probable related to investigational treatment leading to treatment discontinuation. Four grade 3 events (dysphasia, possible related; intracranial hemorrhage unrelated; muscle weakness, unlikely related and hematoma, unrelated). Median PFS was 3.8 months. Median OS was 11 months. RNA sequencing in tumor samples and correlation with cytokine levels in serum is currently been analyzed. CONCLUSION Tumor lysate pulsed DC vaccination demonstrates acceptable safety and tolerability in high-grade glioma patients. Evaluations of integrating molecular profiling RNA sequencing information and cytokine levels to identify potential subset of patients with significant clinical benefit will be provided.

Temozolomide in Malignant Gliomas of Childhood: A United Kingdom Children’s Cancer Study Group and French Society for Pediatric Oncology Intergroup Study

2002 ◽  
Vol 20 (24) ◽  
pp. 4684-4691 ◽  
Author(s):  
L. S. Lashford ◽  
P. Thiesse ◽  
A. Jouvet ◽  
T. Jaspan ◽  
D. Couanet ◽  
...  
Keyword(s):  
Response Rate ◽  
Objective Response ◽  
Malignant Gliomas ◽  
High Grade Glioma ◽  
Study Cohort ◽  
High Grade ◽  
French Society ◽  
Significant Treatment ◽  
Best Response ◽  
Daily Schedule

PURPOSE: To determine the response rate of the malignant gliomas of childhood to an oral, daily schedule of temozolomide. PATIENTS AND METHODS: A multicenter, phase II evaluation of an oral, daily schedule of temozolomide (200 mg/m2 on 5 consecutive days) was undertaken in children with relapsed or progressive, biopsy-proven, high-grade glioma (arm A) and progressive, diffuse, intrinsic brainstem glioma (arm B). Evidence of activity was defined by radiologic evidence of a sustained reduction in tumor size on serial magnetic resonance imaging scans. RESULTS: Fifty-five patients were recruited (34 to arm A and 21 to arm B) and received 215 cycles of chemotherapy. Grade 3/4 thrombocytopenia was the most frequent toxic event (7% of cycles). Prolonged myelosuppression resulted in significant treatment delays and dose reductions (17% and 22% of cycles, respectively). Two toxic deaths were documented and were related to myelosuppression and sepsis in one patient and pneumonia in a second. The overall (best) response rate was 12% for arm A (95% confidence interval [CI], 3 to 28 in the study cohort, and 2 to 31 for eligible patients) and 5% and 6%, respectively, for arm B (95% CI, 0 to 26 in the study cohort, and 0 to 27 for eligible patients). Stabilization of disease was also documented and was most noteworthy for brainstem gliomas, where two patients achieved both radiologic static disease and discontinued steroid medication. CONCLUSION: Despite moderate toxicity, objective response rates to temozolomide have been low, indicating that temozolomide has minimal activity in the high-grade gliomas of childhood.

scholarly journals Reduction of exposure to blood donors in preterm infants submitted to red blood cell transfusions using pediatric satellite packs

2013 ◽  
Vol 31 (3) ◽  
pp. 285-292 ◽  
Author(s):  
Cristina Lika Uezima ◽  
Ariane Moreira Barreto ◽  
Ruth Guinsburg ◽  
Akemi Kuroda Chiba ◽  
José Orlando Bordin ◽  
...  
Keyword(s):  
Birth Weight ◽  
Preterm Infants ◽  
Blood Donor ◽  
Blood Donors ◽  
Newborn Infants ◽  
Median Number ◽  
Erythrocyte Transfusion ◽  
Factors Associated ◽  
Group 2 ◽  
Group 1

OBJECTIVE: In preterm newborn infants transfused with erythrocytes stored up to 28 days, to compare the reduction of blood donor exposure in two groups of infants classified according to birth weight. METHODS: A prospective study was conducted with preterm infants with birth weight <1000g (Group 1) and 1000-1499g (Group 2), born between April, 2008 and December, 2009. Neonates submitted to exchange transfusions, emergency erythrocyte transfusion, or those who died in the first 24 hours of life were excluded. Transfusions were indicated according to the local guideline using pediatric transfusion satellite bags. Demographic and clinical data, besides number of transfusions and donors were assessed. . Logistic regression analysis was performed to determine factors associated with multiple transfusions. RESULTS: 30 and 48 neonates were included in Groups 1 and 2, respectively. The percentage of newborns with more than one erythrocyte transfusion (90 versus 11%), the median number of transfusions (3 versus 1) and the median of blood donors (2 versus 1) were higher in Group 1 (p<0.001), compared to Group 2. Among those with multiple transfusions, 14 (82%) and one (50%) presented 50% reduction in the number of blood donors, respectively in Groups 1 and 2. Factors associated with multiple transfusions were: birth weight <1000g (OR 11.91; 95%CI 2.14-66.27) and presence of arterial umbilical catheter (OR 8.59; 95%CI 1.94-38.13), adjusted for confounders. CONCLUSIONS: The efficacy of pediatrics satellites bags on blood donor reduction was higher in preterm infants with birth weight <1000g.

scholarly journals OS3.6 Prediagnostic symptoms and signs of adult glioma: the patients’ view

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii9-iii10
Author(s):  
M C M Peeters ◽  
L Dirven ◽  
J A F Koekkoek ◽  
E G Gortmaker ◽  
L Fritz ◽  
...  
Keyword(s):  
Health Care ◽  
Health Care Professionals ◽  
High Grade Glioma ◽  
Median Number ◽  
Low Grade ◽  
High Grade ◽  
Health Care Usage ◽  
Patients Experience ◽  
Symptoms And Signs ◽  
Chronic Complaints

Abstract BACKGROUND Little is known about the symptoms and signs glioma patients experience in the year before diagnosis, either or not resulting in health care usage. The objective of this study was to determine the incidence of several symptoms and signs glioma patients experienced in the year prior to diagnosis, as well as visits to a general practitioner (GP) related to these issues. MATERIAL AND METHODS This was a cross-sectional study, including adults diagnosed with a glioma <12 months ago. Patients were asked to complete a 30-item study-specific questionnaire, if possible with input of a proxy, focusing on symptoms and signs they experienced in the 12 months before diagnosis. For each indicated symptom/sign, patients were asked whether they consulted the GP for this issue. In addition, the presence of comorbidity and other chronic complaints were assessed, as well as consulted health care professionals (HCPs) in the year prior to diagnosis. The statistical analyses were corrected for multiple testing. RESULTS Between July 2016 and March 2019, 58 patients completed the questionnaires, 54 (93%) with input of a proxy. Forty-one (72%) patients were men, with a median age of 60 years (range 43–78), and the median time since diagnosis was 4 months (range 1–12). Forty (69%) patients had a comorbidity or chronic complaint, and the median number of consulted HCPs was 2 (range 0–8). The median number of symptoms/signs experienced in the year before diagnosis was 8 (range 2–19) in low-grade and 5 (range 0–24) in high-grade glioma (p=0.258). The five most frequently mentioned problems were fatigue (34/58, 59%), mental tiredness (28/58, 48%), sleeping disorder (23/58, 40%), headache (22/58, 38%) and stress (20/58, 34%), with no differences between low- and high grade glioma. Twenty-five (43%) patients had visited the GP with at least one issue. We found that patients who did consult their GP reported significantly more often muscle weakness (11 vs 3, p=0.002), paralysis in for example a hand or leg (10 vs 3, p=0.006), or a change in consciousness (9 vs 3, p=0.013) compared to those that did not consult the GP. However, they did not differ with respect to the number of symptoms (median 7 vs 5), comorbidities and chronic complaints (median 1 vs 1), or overall health care usage (median 3 vs 2). CONCLUSION Glioma patients experience a range of problems in the year prior to diagnosis, but patients who consult the GP report significantly more often neurological problems.

KS02.4.A Olaparib in Recurrent IDH-mutant High-Grade Glioma (OLAGLI)

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii4-ii4
Author(s):  
F Ducray ◽  
M Sanson ◽  
O Chinot ◽  
M Fontanilles ◽  
R Rivoirard ◽  
...  
Keyword(s):  
Median Time ◽  
High Grade Glioma ◽  
Median Number ◽  
Parp Inhibition ◽  
Low Grade ◽  
Type I ◽  
High Grade ◽  
Rano Criteria ◽  
Anaplastic Gliomas ◽  
New Treatments

Abstract BACKGROUND There is a need to develop new treatments in IDH-mutant high-grade gliomas recurring after radiotherapy and chemotherapy. Based on preclinical studies showing that IDH-mutant tumors could be vulnerable to PARP inhibition we launched a phase II study to test the efficacy of olaparib (Lynparza) monotherapy in this population. METHODS Adults with recurrent high-grade IDH-mutant gliomas after radiotherapy and at least one line of alkylating chemotherapy (PCV or TMZ), KPS &gt; 60, normal organ function were enrolled. The primary endpoint was 6 months PFS according to RANO criteria. Patients were treated with olaparib 300 mg twice daily. We used a single-stage Fleming design with p0 = 30%, p1 = 50%, a type I unilateral error rate of 5% and a power of 80%. RESULTS 35 patients with recurrent IDH-mutant gliomas (IDH1R132H-mutant n = 32, other IDH mutation n = 3, 1p/19 codeleted n = 16, 1p/19q non-codeleted n = 14) were enrolled (malignantly transformed low-grade gliomas n = 21, anaplastic gliomas n = 8, glioblastomas n = 6). Median time since diagnosis was 7.4 years (1–22 years), median time since radiotherapy was 2.8 years (0.6–18 years), median number of previous chemotherapy lines was 2 (1–5). With a median follow-up of 11 months, 30 patients had stopped treatment due to tumor progression and 2 patients were still on treatment 16 to 18 months after treatment start. At 6 months, 11/35 patients were progression-free (31 %). According to RANO criteria, based on local investigator analysis, 2 patients (5%) had a partial response and 14 patients a stable disease (37%) with a median duration of response of 9 months (4–18+). Median PFS and OS were 2.3 and 15.9 months and were similar in 1p/19q codeleted and non-codeleted patients. A grade 3 olaparib-related adverse event was observed in 5 patients (14%, lymphopenia n = 3, fatigue n = 2, diarrhea n = 1) and a grade 2 in 15 patients (43%), most frequently consisting in fatigue (23%), gastrointestinal disorders (20%) and lymphopenia (20%). No patient definitively stopped olaparib due to side effects. CONCLUSIONS In this heavily pre-treated population of recurrent IDH-mutant gliomas, olaparib monotherapy was well tolerated and resulted in some activity supporting its evaluation in association with alkylating chemotherapy in recurrent IDH-mutant gliomas in future studies.

scholarly journals Effect of Timing of Ondansetron Administration on Incidence of Postoperative Vomiting in Paediatric Strabismus Surgery

2000 ◽  
Vol 28 (1) ◽  
pp. 27-30 ◽  
Author(s):  
R. Madan ◽  
T. Perumal ◽  
K. Subramaniam ◽  
D. Shende ◽  
S. Sadashivam ◽  
...  
Keyword(s):  
Muscle Relaxation ◽  
Demographic Data ◽  
Median Number ◽  
Strabismus Surgery ◽  
First Episode ◽  
Antiemetic Efficacy ◽  
Number Of Patients ◽  
Group 2 ◽  
Mean Time ◽  
Group 1

This prospective, randomized, double-blinded study evaluated the effect of the timing of ondansetron administration on its antiemetic efficacy in children undergoing elective strabismus surgery. One hundred and twenty children aged one to 15 years, ASA physical status 1 or 2, were randomly allocated to receive intravenous ondansetron 100 μg/kg either at induction (Group 1) or at the end of the surgery (Group 2). All patients had general anaesthesia induced and maintained with nitrous oxide and halothane, muscle relaxation with vecuronium, endotracheal intubation, reversal with neostigmine and glycopyrrolate, and pethidine 0.5 mg/kg analgesia. Episodes of nausea and vomiting were evaluated at 0 to 2, 2 to 6 and 6 to 24 hour intervals by a blinded observer. Demographic data, duration of anaesthesia, type of surgery, incidence of previous postoperative nausea or vomiting and motion sickness and number of patients who developed oculocardiac reflex requiring atropine treatment were similar in both groups. The incidence of emesis in the first 24 hours following surgery was similar in both groups (35% Group 1, 33.3% Group 2, P=1.00). Severity of emesis (median number of emetic episodes, rescue antiemetic requirement and mean time to the onset of first episode of emesis) and mean time to discharge from the post anaesthesia care unit were also similar in the two groups. We conclude that the timing of ondansetron administration either before or after the surgical manipulation of extraocular muscles had similar antiemetic efficacy following strabismus surgery in children.

Sign in / Sign up

Export Citation Format

Share Document