Comparison of two dose calculation methods of intra-arterial carboplatin in the treatment of recurrent glioblastoma multiforme.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13503-e13503
Author(s):  
Brigitte Boilard ◽  
Alexandra Hinse ◽  
Karianne Beaulieu ◽  
Florence Marcotte ◽  
David Fortin ◽  
...  
Keyword(s):  
Prospective Trial ◽  
Area Under The Curve ◽  
Dose Calculation ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
Hematologic Toxicity ◽  
Calculation Methods ◽  
Recurrent Glioblastoma Multiforme ◽  
Free Survival ◽  
The Impact

e13503 Background: Glioblastoma is a deadly brain cancer, and as part of the natural evolution, its relapses will mostly occur 32 to 36 weeks after the initial diagnosis. The standard of care for recurrent glioblastomas is not well defined and multiple options exist. Intra-arterial chemotherapy as one option is currently practiced at the Centre hospitalier universitaire de Sherbrooke, the only center doing this procedure in Canada. The aim of this study is to evaluate the impact of using the area under the curve (AUC) or body surface area (BSA) dosing formula to guide intra-arterial carboplatin administration. It was designed to explore the relation of two dose calculation methods on efficacy and toxicity, determined by progression-free survival (PFS) and hematologic toxicity, respectively. Methods: A retrospective observational study was conducted, which includes adult in-patients who received intra-arterial carboplatin for recurrent glioblastoma from June 1st, 2000 to December 31st, 2017. It examined the associations of the method used to calculate the doses, in mg or mg/mL x min-1, with clinical outcomes. Results: One hundred ninety patients were included in the analysis. For the primary endpoint, an exposure greater than 6 of AUC was found potentially harmful in terms of efficacy compared to AUC under 6 (HR 0.529, p = 0.0044). In terms of toxicity, a higher AUC is highlighted to correlate with a slightly higher incidence of thrombocytopenia and neutropenia (OR 1.051 p = 0.0271; OR 1.072 p = 0.049). No significant association between toxicity and dose calculated with BSA could be established. Conclusions: AUC greater than 6 is detrimental in terms of effectiveness according to progression free survival. Moreover, AUC could be used to predict neutropenia and thrombocytopenia. However no significant predictions were found using BSA method. We recommend the use of AUC method in intra-arterial carboplatin instead of BSA method since the latter was not statistically related to toxicity. A prospective trial comparing the two dosage methods would be needed.

Effect of an individualized dose/schedule strategy for sunitinib in metastatic renal cell cancer (mRCC) on progression-free survival (PFS): Correlation with dynamic microbubble ultrasound (DCE-US) data.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 356-356 ◽  
Author(s):  
G. A. Bjarnason ◽  
B. Khalil ◽  
R. Williams ◽  
J. M. Hudson ◽  
B. Lloyd ◽  
...  
Keyword(s):  
Clear Cell ◽  
Cell Cancer ◽  
Prospective Trial ◽  
Area Under The Curve ◽  
Progression Free Survival ◽  
Dose Schedule ◽  
Pharmacokinetic Data ◽  
Free Survival ◽  
D 43

356 Background: Sunitinib area under the curve (AUC) correlates with response and PFS (Houk et al). Current recommendations for dose modification do not take this into account. Methods: A single center retrospective review identified mRCC patients (pts) where individualized (individ) sunitinib dose/schedule modifications (DSM) were used to maximize dose and minimize time off therapy (Rx). Pts were started on 50 mg 28 days (d) on/14 d off. DSM were done to keep toxicity (fatigue, skin, GI) at ≤ grade-2. DSM-1 was 50 mg 14 d/7 d with individ increases in d on Rx based on toxicity. DSM-2 was 50 mg 7 d/7 d with individ increases in d on Rx. DSM-3 was 37.5 mg continuously with individ 7 d breaks. DSM-4 was 25 mg continuously with individ 7 d breaks. Results: In 171 pts; median age was 60y; 20% good, 60% intermediate, 20% poor prognosis by Heng criteria; 80% had nephrectomy; 79% clear cell histology; 60% were previously untreated. At a median follow-up of 10.7 months (mo), overall median PFS was 7.9 mo. Of 39 pts still on therapy, 37 were on a DSM Rx. Pts were allocated to three groups based on the dose/schedule used for the longest time. The PFS/response% (PR+SD) for each group was 4.4 mo/65.6% (standard 50 mg 28 d/14 d; 43 pts), 8.0 mo/78.2% (DSM-1/DSM-2; 69 pts) and 10.4 mo/81.3% (DSM-3/DSM-4; 59 pts) with improved PFS (p=0.001) in both DSM groups vs. the standard schedule but no difference in response. 30 pts were studied by DCE-US at baseline, and after 7 d and 14 d on Rx or after 14 d and 28 d on Rx. In responding pts, tumor blood volume decreased at d 7 and again at d 14 vs. baseline but was stable or increased at d 28 vs. d 14. A rebound was seen after 14 d off Rx. Conclusions: Based on the U.S. data, previous pharmacokinetic data (steady state at 10-14 d) and this clinical data, starting pts on 50 mg 14 d/7 d followed by individ DSM may be safe and active. This DSM strategy, was associated with a favorable toxicity profile, apparent improvement in PFS and a good PR+SD rate in a group of unselected mRCC pts, warranting confirmation in a prospective trial. Pts that tolerate 50 mg 28 d/14 d with minimum toxicity may need dose escalation and/or less time off therapy to optimize PFS. [Table: see text]

Phase II clinical trial of Wilms tumor 1 peptide vaccination for patients with recurrent glioblastoma multiforme

2008 ◽  
Vol 108 (5) ◽  
pp. 963-971 ◽  
Author(s):  
Shuichi Izumoto ◽  
Akihiro Tsuboi ◽  
Yoshihiro Oka ◽  
Tsuyoshi Suzuki ◽  
Tetsuo Hashiba ◽  
...  
Keyword(s):  
Partial Response ◽  
Wilms Tumor ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
Vaccine Therapy ◽  
Recurrent Glioblastoma Multiforme ◽  
Free Survival ◽  
Clinical Responses ◽  
Positive Recurrent ◽  
Recurrent Gbm

Object The object of this study was to investigate the safety and clinical responses of immunotherapy targeting the WT1 (Wilms tumor 1) gene product in patients with recurrent glioblastoma multiforme (GBM). Methods Twenty-one patients with WT1/HLA-A*2402–positive recurrent GBM were included in a Phase II clinical study of WT1 vaccine therapy. In all patients, the tumors were resistant to standard therapy. Patients received intra-dermal injections of an HLA-A*2402–restricted, modified 9-mer WT1 peptide every week for 12 weeks. Tumor size, which was obtained by measuring the contrast-enhanced area on magnetic resonance images, was determined every 4 weeks. The responses were analyzed according to Response Evaluation Criteria in Solid Tumors (RECIST) 12 weeks after the initial vaccination. Patients who achieved an effective response continued to be vaccinated until tumor progression occurred. Progression-free survival and overall survival after initial WT1 treatment were estimated. Results The protocol was well tolerated; only local erythema occurred at the WT1 vaccine injection site. The clinical responses were as follows: partial response in 2 patients, stable disease in 10 patients, and progressive disease in 9 patients. No patient had a complete response. The overall response rate (cases with complete or partial response) was 9.5%, and the disease control rate (cases with complete or partial response as well as those in which disease was stable) was 57.1%. The median progression-free survival (PFS) period was 20.0 weeks, and the 6-month (26-week) PFS rate was 33.3%. Conclusions Although a small uncontrolled nonrandomized trial, this study showed that WT1 vaccine therapy for patients with WT1/HLA-A*2402–positive recurrent GBM was safe and produced a clinical response. Based on these results, further clinical studies of WT1 vaccine therapy in patients with malignant glioma are warranted.

Safety and Efficacy of Temozolomide in Patients With Recurrent Anaplastic Oligodendrogliomas After Standard Radiotherapy and Chemotherapy

2001 ◽  
Vol 19 (9) ◽  
pp. 2449-2455 ◽  
Author(s):  
Oliver-Louis Chinot ◽  
Stephane Honore ◽  
Henry Dufour ◽  
Maryline Barrie ◽  
Dominique Figarella-Branger ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Recurrent Glioblastoma ◽  
Limited Data ◽  
Time To Progression ◽  
Recurrent Glioblastoma Multiforme ◽  
Free Survival ◽  
Grade 3 ◽  
Entire Treatment

PURPOSE: Most primary oligodendrogliomas and mixed gliomas (oligoastrocytoma) respond to treatment with procarbazine, lomustine, and vincristine (PCV), with response rates of approximately 80%. However, limited data on second-line treatments are available in patients with recurrent tumors. A novel second-generation alkylating agent, temozolomide, has recently demonstrated efficacy and safety in patients with recurrent glioblastoma multiforme and anaplastic astrocytoma. This study describes the effects of temozolomide in patients with recurrent anaplastic oligodendroglioma (AO) and anaplastic mixed oligoastrocytoma (AOA). PATIENTS AND METHODS: Forty-eight patients with histologically confirmed AO or AOA who had received previous PCV chemotherapy were treated with temozolomide (150 to 200 mg/m2/d for 5 days per 28-day cycle). The primary end point was objective response. Secondary end points included progression-free survival (PFS), time to progression, overall survival (OS), safety, and tolerability. RESULTS: Eight patients (16.7%) experienced a complete response, 13 patients (27.1%) experienced a partial response (objective response rate, 43.8%), and 19 patients (39.6%) experienced stable disease. For the entire treatment group, median PFS was 6.7 months and median OS was 10 months. For objective responders, median PFS was 13.1 months and median OS was 16 months. For complete responders, PFS was more than 11. 8 months and OS was more than 26 months. Response correlated with improved survival. Temozolomide was safe and well tolerated. Twelve patients developed grade 1/2 thrombocytopenia and three patients developed grade 3/4 thrombocytopenia. CONCLUSION: Temozolomide is safe and effective in the treatment of recurrent AO and AOA.

Reirradiation and chemotherapy with ifosfamide, carboplatin and etoposide (ICE) for recurrent multiforme glioblastoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 12508-12508
Author(s):  
A. Rodica Maricela ◽  
L. N. Minea ◽  
L. Oprea ◽  
T. Georgescu ◽  
I. Isacu ◽  
...  
Keyword(s):  
Treatment Options ◽  
Haematological Toxicity ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
Recurrent Glioblastoma Multiforme ◽  
Free Survival ◽  
Concomitant Radiochemotherapy ◽  
Tumor Bed ◽  
One Year ◽  
Standard Treatment Regimen

12508 Background: Despite different treatment options no standard treatment regimen is yet available for patient with recurrent glioblastoma, and the prognosis remain poor. In our study our aim was to assess the efficacy of a schedule consisted in Ifosfamide plus Carboplatine plus Etoposide in recurrent multiform glioblastoma patients. Methods: Between January 2002 - December 2006 32 patients have been treated for recurrent glioblastoma multiforme. They were 18 male and 14 female, with median age 44.6 years old (range 22–65 years old). The ECOG was 0–1-2 , 12/14/6 patients respectively. 15 of them received chronic corticotherapy. All patients were previously irradiated and they have inoperable recurrences. After the confirmation of recurrence 30 of them could be reirradiated with 30 Gy using conformal beam radiotherapy on the tumor bed. Three weeks after completion of radiotherapy they receive six cycles of chemotherapy consisted in Ifosfamide 1000 mg/sqm day 1–3 + Carboplatin 75 mg/sqm day 1–3 + Etoposide 75 mg/sqm day 1–3 every 4 weeks, according to hematological tolerance. Results: Reirradiation associated with ICE chemotherapy resulted in one complete remission, three partial remission, and 8 stable disease. All responders were 37.5%. 26 patients survived at least six month and 22 of them received all six cycles. One year survival rate was 21.8%. Progression-free survival at six month was 31.25%. The regimen was well tolerated with mild toxicities. Haematological toxicity gr.I-II 8 pts, gr.III-IV 3 pt; nonhaematological toxicity: fatigability gr.I-II 12 pts., gr.III-IV 2 pt, gr.III-IV 1 pt, nausea gr.I-II 9 pts, gr.III-IV 4 pt, renal toxicity grade I-II 3 patients, Neurological toxicity grade I-II 5 patients. Conclusions: The treatment scheme has been well tolerated. Results are similar with PCV regimen, even slightly better. This regimen should be reconsider for concomitant radiochemotherapy. No significant financial relationships to disclose.

Leuven Dose-Dense Paclitaxel/Carboplatin Regimen in Patients With Primary Advanced or Recurrent Endometrial Carcinoma

2009 ◽  
Vol 19 (6) ◽  
pp. 1147-1151 ◽  
Author(s):  
Ingrid Vandenput ◽  
Ignace Vergote ◽  
Karin Leunen ◽  
Patrick Berteloot ◽  
Patrick Neven ◽  
...  
Keyword(s):  
Partial Response ◽  
Stable Disease ◽  
Area Under The Curve ◽  
Progression Free Survival ◽  
Complete Response ◽  
Hematologic Toxicity ◽  
Free Survival ◽  
Group 2 ◽  
Dose Dense ◽  
Group 1

Objective:To evaluate the response of dose-dense paclitaxel/carboplatin (TC) patients with primarily advanced or recurrent endometrial cancer.Methods:Six courses of paclitaxel (90 mg/m2) and carboplatinum (area under the curve, 4) on days 1 and 8 every 3 weeks were administered. Response rates were evaluated according to the response evaluation criteria in solid tumors.Results:Dose-dense TC was administered to 42 patients. The median age was 63.9 years (range, 41-81 years). The main histopathologic types were serous/clear cell (n = 27) and endometrioid (n = 13). The patients were divided in 2 groups: chemotherapy-naive group (n = 28, group 1) and a group with previous chemotherapy (n = 14, group 2).The responses for group 1 were as follows: 11 (39 %) complete response, 9 (32%) partial response, and 2 (7%) stable disease. The responses for group 2 were 1 (7%) complete response, 2 (14%) partial response, and 6 (43%) stable disease. Treatment-related death occurred in 1 patient (7%) because of neutropenia and nephrotoxicity.Progression-free survival for group 1 was 10 months (range, 4-19 months). At time of analysis, 57% of the patients were still alive after a median follow-up of 10 months (range, 4-21 months). Progression-free survival for group 2 was 11 months (range, 4-19 months).Because of grades 3 and 4 hematologic toxicity, treatment adjustments were as follows: 49 (18%) and 18 (19%) dose reductions (carboplatin area under the curve, 2-3), 35 (13%) and 14 (15%) dose delays, and 8 (3%) and 6 (6%) treatments were not administered on day 8 for groups 1 and 2, respectively.Conclusions:Administration of dose-dense TC resulted in a response rate of 71% in chemotherapy-naive patients. Treatment modifications due to toxicity were frequent, but severe complications such as neutropenic fever occurred in a similar incidence as other reported 3-weekly regimens.

Bevacizumab: A Treatment Option for Recurrent Glioblastoma Multiforme

2008 ◽  
Vol 42 (10) ◽  
pp. 1486-1490 ◽  
Author(s):  
Larry W Buie ◽  
John M Valgus
Keyword(s):  
Clinical Trials ◽  
Growth Factor ◽  
Glioblastoma Multiforme ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
Data Sources ◽  
Recurrent Glioblastoma Multiforme ◽  
Free Survival ◽  
Anti Vegf ◽  
Recurrent Gbm

Objective: To review the available literature evaluating the effect of bevacizumab on progression-free survival when used in combination with irinotecan for recurrent glioblastoma multiforme (GBM). Data Sources: Searches of MEDLINE (1966-June 2008), the Cochrane Library. and International Pharmaceutical Abstracts (1970-June 2008) were conducted using the terms bevacizumab. irinotecan, and glioblastoma multiforme. Study Selection And Data Extraction: The search was limited to studies conducted in humans. All articles identified trom the data sources were evaluated. All clinical trials evaluating the efficacy and safety of bevacizumab in the treatment of recurrent GBM were included in the review. Data Synthesis: Hypoxia, mutagenesis, and the secretion of various growth (actors can all lead to production of vascular endothelial growth factor (VEGF), a proangiogenic growth factor, and angiogenesis in GBM. Neoplastic progression is dependent on angiogenesis, and anti-VEGF therapy has been successful in multiple disease states. However, there are currently no available anti-VEGF therapies approved tor treatment of GBM. Bevacizumab is a humanized monoclonal antibody that binds to and inhibits the activity of VEGF. When compared with data from clinical trials that use single chemotherapeutic agents in recurrent GBM, the addition of bevacizumab to cytotoxic chemotherapy, such as irinotecan, appears to improve progression-Iree survival in patients progressing on the standard of care, with a 6-month progression-free survival rate of 46%. Bevacizumab is well tolerated by most patients, with modest risk (11% tn Phase 2 trials) of venous thromboembolism. Conclusions: Although the combination of bevacizumab and irinotecan is producing positive results in patients with recurrent GBM, larger, randomized clinical trials need to be performed to determine the magnitude of the benefit from bevacizumab. Bevacizumab administered biweekly at a dose of 10 mg/kg in combination with irinotecan may improve progression-free survival.

scholarly journals Rekurrens glioblastomában szenvedő betegek kezelése bevacizumab-monoterápiával

2016 ◽  
Vol 157 (13) ◽  
pp. 500-503 ◽  
Author(s):  
Dániel Sinkó ◽  
Csaba Nemeskéri
Keyword(s):  
Overall Survival ◽  
Glioblastoma Multiforme ◽  
Median Survival ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
Recurrent Glioblastoma Multiforme ◽  
Free Survival

Introduction: The prognosis of patients with recurrent glioblastoma is poor, as the median survival does not exceed 6 months. Aim: The aim of this study was to evaluate the efficacy of bevacizumab monotherapy in patients with recurrent glioblastoma multiforme. Method: From April, 2012 to June, 2015, 40 patients with recurrent glioblastoma multiforme were treated with bevacizumab in a dose of 10 mg/kg every 2 weeks. Results: The average progression-free survival was 6.4 months (2–22 months), and the 6-month progression-free survival was 42.5%. The six-month overall survival was 82.5%, which corresponds to those published in the literature. Conclusions: Bevacizumab monotherapy improves progression-free survival in patients with recurrent glioblastoma multiforme. Orv. Hetil., 2016, 157(13), 500–503.

First-Line Chemotherapy With Cisplatin Plus Fractionated Temozolomide in Recurrent Glioblastoma Multiforme: A Phase II Study of the Gruppo Italiano Cooperativo di Neuro-Oncologia

2004 ◽  
Vol 22 (9) ◽  
pp. 1598-1604 ◽  
Author(s):  
Alba A. Brandes ◽  
Umberto Basso ◽  
Michele Reni ◽  
Francesca Vastola ◽  
Alicia Tosoni ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
Hematologic Toxicity ◽  
Recurrent Glioblastoma Multiforme

Purpose Cisplatin and temozolomide (TMZ) are active in glioblastoma multiforme (GBM), with different profiles of toxicity. A bid regimen of TMZ achieves a strong inhibition of O6-alkylguanine DNA-alkyl transferase (AGAT), and cisplatin reduces AGAT activity in vitro, suggesting a possible synergic interaction. The primary end point of the present multicenter phase II study was progression-free survival (PFS) at 6 months (PFS-6); secondary end points included response, toxicity, and overall survival. Patients and Methods Chemotherapy-naive patients with GBM who experienced disease recurrence or progression after surgery and standard radiotherapy were eligible. Chemotherapy cycles consisted of cisplatin 75 mg/m2 on day 1, TMZ 130 mg/m2 bolus followed by nine doses of 70 mg/m2 every 12 hours (total of 5 days) from day 2 every 4 weeks. In the absence of hematologic toxicity, TMZ was escalated to 1,000 mg/m2 in 5 days. Results A total of 50 patients (median age, 53.4 years; range, 27 to 70 years; median Karnofsky performance status, 80; range, 60 to 100) were accrued in the study. PFS-6 was 34% (95% CI, 23% to 50%), and PFS-12 was 4% (95% CI, 0.3% to 16%). Median PFS was 18.4 weeks (95% CI, 13 to 25.9 weeks). Among 49 assessable patients, one complete response and nine partial responses were obtained, with an overall response rate of 20.4% (95% CI, 7.7% to 33%). Among 203 treatment cycles delivered, the most common grade 3 or grade 4 events included granulocytopenia in 7.9% of cycles, thrombocytopenia in 4%, and neurologic toxicity in three patients (6%). Conclusion The new cisplatin plus bid TMZ regimen appears active in chemotherapy-naive patients with recurrent GBM and incurs an acceptable toxicity.

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