Bevacizumab, a monoclonal antibody to vascular endothelial growth factor (VEGF), and irinotecan for treatment of malignant gliomas

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 1506-1506 ◽  
Author(s):  
J. J. Vredenburgh ◽  
A. Desjardins ◽  
J. E. Herndon ◽  
J. Quinn ◽  
J. Rich ◽  
...  
Keyword(s):  
Malignant Gliomas ◽  
Progression Free Survival ◽  
Vegf Receptor ◽  
Free Survival ◽  
Topoisomerase 1 ◽  
Median Progression Free Survival ◽  
Thrombotic Complications ◽  
High Concentrations ◽  
Hip Stabilization ◽  
Chemotherapy Patients

1506 Background: The prognosis for recurrent malignant gliomas is poor, with a median survival <12 months, median progression-free survival <12 weeks and response rates <20%. Malignant gliomas have high concentrations of VEGF receptors, and the higher the VEGF receptor concentration, the worse the prognosis. Bevacizumab is a humanized IgG1 monoclonal antiblody to VEGF, which is synergistic with chemotherapy for most malignancies. Irinotecan is a topoisomerase 1 inhibitor, and has modest activity against recurrent malignant gliomas. Methods: We report a FDA approved phase II trial of bevacizumab and irinotecan for the treatment of recurrent malignant gliomas. 32 patients were enrolled, 23 with grade IV tumors (glioblastoma multiforme) and 9 with grade III tumors (anaplastic astrocytomas or oligodendrogliomas). All the patients had progressive disease and every patient had received prior radiation therapy and chemotherapy. Patients were treated every other week with bevacizumab 10 mg/kg and irinotecan 125 mg/m2 for patients not taking enzyme inducing anti-epileptic drugs or 340 mg/m2 for patients taking enzyme inducing anti-epileptic drugs. Results: The regimen was well tolerated with no CNS hemorrhages or >grade 1 systemic hemorrhages. Four patients were taken off study for thrombotic complications, 2 pulmonary emboli, 1 deep venous thrombus, and one thrombotic stroke. Two patients were discontinued secondary to grade 2 proteinuria and three were discontinued because they required non-neurosurgical surgery, appendectomy, repair of anal fissures and hip stabilization. The response rate was 63% (19 PRs and 1 CR). The median progression-free survival is 24 weeks. The median overall survival has not been reached, and exceeds 6 months. There have been ten deaths due to disease progression. Conclusions: The combination of bevacizumab and irinotecan is safe and one of the most active regimens against malignant gliomas. [Table: see text]

scholarly journals Phase II Study of Fenretinide (NSC 374551) in Adults With Recurrent Malignant Gliomas: A North American Brain Tumor Consortium Study

2004 ◽  
Vol 22 (21) ◽  
pp. 4282-4289 ◽  
Author(s):  
Vinay K. Puduvalli ◽  
W.K. Alfred Yung ◽  
Kenneth R. Hess ◽  
John G. Kuhn ◽  
Morris D. Groves ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Phase Ii Study ◽  
Malignant Gliomas ◽  
Progression Free Survival ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
Anaplastic Gliomas ◽  
Higher Doses

Purpose Fenretinide induces apoptosis in malignant gliomas in vitro. This two-stage phase II trial was conducted to determine the efficacy of fenretinide in adults with recurrent malignant gliomas. Patients and Methods Twenty-two patients with anaplastic gliomas (AG) and 23 patients with glioblastoma (GBM) whose tumors had recurred after radiotherapy and no more than two chemotherapy regimens were enrolled. Fenretinide was given orally on days 1 to 7 and 22 to 28 in 6-week cycles in doses of 600 or 900 mg/m2 bid. Results Six of 21 (29%) patients in the AG arm and two of 23 (9%) patients in the GBM arm had stable disease at 6 months. One patient with AG treated at 900 mg/m2 bid dosage had a partial radiologic response. Median progression-free survival (PFS) was 6 weeks for the AG arm and 6 weeks for the GBM arm. PFS at 6 months was 10% for the AG arm and 0% for the GBM arm. Grade 1 or 2 fatigue, dryness of skin, anemia, and hypoalbuminemia were the most frequent toxicities reported. The trial was closed after the first stage because of the inadequate activity at the fenretinide doses used. The first-administration mean plasma Cmax for fenretinide was 832 ± 360 ng/mL at the 600 mg/m2 bid dosage and 1,213 ± 261 ng/mL at the 900 mg/m2 bid dosage. Conclusion Fenretinide was inactive against recurrent malignant gliomas at the dosage used in this trial. However, additional studies using higher doses of the agent are warranted based on the tolerability of the agent and the potential for activity of a higher fenretinide dosage, as suggested in this trial.

scholarly journals Current FDA-Approved Therapies for High-Grade Malignant Gliomas

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 324
Author(s):  
Jacob P. Fisher ◽  
David C. Adamson
Keyword(s):  
Controlled Trial ◽  
Malignant Gliomas ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
High Grade ◽  
Tumor Treatment ◽  
Free Survival ◽  
Randomized Controlled ◽  
Significant Survival ◽  
One Year

The standard of care (SOC) for high-grade gliomas (HGG) is maximally safe surgical resection, followed by concurrent radiation therapy (RT) and temozolomide (TMZ) for 6 weeks, then adjuvant TMZ for 6 months. Before this SOC was established, glioblastoma (GBM) patients typically lived for less than one year after diagnosis, and no adjuvant chemotherapy had demonstrated significant survival benefits compared with radiation alone. In 2005, the Stupp et al. randomized controlled trial (RCT) on newly diagnosed GBM patients concluded that RT plus TMZ compared to RT alone significantly improved overall survival (OS) (14.6 vs. 12.1 months) and progression-free survival (PFS) at 6 months (PFS6) (53.9% vs. 36.4%). Outside of TMZ, there are four drugs and one device FDA-approved for the treatment of HGGs: lomustine, intravenous carmustine, carmustine wafer implants, bevacizumab (BVZ), and tumor treatment fields (TTFields). These treatments are now mainly used to treat recurrent HGGs and symptoms. TTFields is the only treatment that has been shown to improve OS (20.5 vs. 15.6 months) and PFS6 (56% vs. 37%) in comparison to the current SOC. TTFields is the newest addition to this list of FDA-approved treatments, but has not been universally accepted yet as part of SOC.

TIVO-3: Tivozanib in patients with advanced renal cell carcinoma (aRCC) who have progressed after treatment with axitinib.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 278-278
Author(s):  
Brian I. Rini ◽  
Sumanta K. Pal ◽  
Bernard Escudier ◽  
Michael B. Atkins ◽  
Thomas E. Hutson ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Risk Category ◽  
Vegf Receptor ◽  
Free Survival ◽  
Prior Therapy ◽  
Third Line ◽  
Line Setting ◽  
Clinical Trial Information

278 Background: Tivozanib (T) is a potent and highly selective VEGF receptor (R) tyrosine kinase inhibitor in clinical development for RCC. Axitinib is also a potent and selective VEGF-R inhibitor now commonly part of front-line aRCC treatment. The activity of T after axitinib has not been previously defined. The activity of T after prior therapy types including axitinib is of clinical relevance. Methods: The pivotal TIVO-3 study enrolled subjects with mRCC who failed 2 or 3 prior systemic regimens, one of which included a VEGFR TKI, stratified by IMDC risk category and type of prior therapy (two TKIs; TKI plus checkpoint; TKI + other) then randomized in a 1:1 ratio to T or S. The primary objective of the overall trial was to compare progression free survival (PFS) by blinded independent radiological review. Patients with prior axitinib received as monotherapy in the second or third line setting and other predefined subgroups were reviewed for outcome with T. Results: Patients treated with T after prior axitinib had a PFS of 5.5 months and an ORR of 13% compared to 3.7 months and 8% for patients treated with S. Other subgroups are presented in the table below. Clinical trial information: NCT02627963 . Conclusions: Tivozanib improved PFS vs. sorafenib in patients who have progressed after multiple VEGFR-TKIs, including patients with prior second or third line axitinib treatment. These results suggest differential activity from tivozanib and axitinib despite both being potent and selective VEGF-R inhibitors. [Table: see text]

Use of nab-paclitaxel and gemcitabine in pancreatic cancer without granulocyte colony-stimulating factor: A multicenter real-world experience

2021 ◽  
pp. 107815522110386
Author(s):  
Angela Chen ◽  
Vincent H Ha ◽  
Sunita Ghosh ◽  
Carole R Chambers ◽  
Michael B Sawyer
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Median Overall Survival ◽  
Progression Free Survival ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Free Survival ◽  
Colony Stimulating Factors ◽  
Median Progression Free Survival ◽  
Stimulating Factor

Introduction The metastatic pancreatic adenocarcinoma clinical trial (MPACT) trial established gemcitabine (gem) and nab-paclitaxel (nab) as a standard treatment for pancreatic cancer utilizing granulocyte colony-stimulating factors to manage neutropenia. This was a challenge for jurisdictions that do not use granulocyte colony-stimulating factors in palliative settings. We developed dosage guidelines to dose modify gem and nab without granulocyte colony-stimulating factors. We undertook a retrospective review to determine the efficacy and safety of these dose adjustment guidelines in the real world. Methods A multi-centered, retrospective chart review was performed on pancreatic patients between December 1, 2014, and August 21, 2018. Provincial electronic medical health records were reviewed. Using Log-rank statistics we determined the patient's progression-free survival and overall survival. Results Of 248 patients, 209 met patient selection criteria. Patients were excluded if they were lost to follow-up, on gem alone prior to nab/gem combination therapy or did not receive nab or gem. Patients who received nab/gem as first-line therapy had a median progression-free survival of 6.3 months (95% CI, 5.1–7.4), and median overall survival of 11.1 months (95% CI, 9.5–12.8). Those who received gem/nab in the second line had a median progression-free survival of 4.6 months (95% CI, 2.8–6.5), and median overall survival of 19.3 months (95% CI, 12.6–26.0). Conclusions The patient’s progression-free survival and overall survival taking nab/gem using our dose modification algorithm were equivalent or superior to the MPACT trial's progression-free survival and overall survival. Gem/nab can be given by our dose modification scheme without granulocyte colony-stimulating factor.

scholarly journals Sodium Fluorescein-Guided Resection under the YELLOW 560 nm Surgical Microscope Filter in Malignant Gliomas: Our First 38 Cases Experience

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Ningning Zhang ◽  
Hailong Tian ◽  
Dezhang Huang ◽  
Xianbing Meng ◽  
Wenqiang Guo ◽  
...  
Keyword(s):  
Malignant Gliomas ◽  
Progression Free Survival ◽  
Extent Of Resection ◽  
Subtotal Resection ◽  
Sodium Fluorescein ◽  
Who Grade ◽  
Free Survival ◽  
Surgical Microscope ◽  
Yellow 560 ◽  
High Fluorescence

Objective. Sodium fluorescein (FL) had been safely used in fluorescence-guided microsurgery for imaging various brain tumors. Under the YELLOW 560 nm surgical microscope filter, low-dose FL as a fluorescent dye helps in visualization. Our study investigated the safety and efficacy of this innovative technique in malignant glioma (MG) patients. Patients and Method. 38 patients suffering from MGs confirmed by pathology underwent FL-guided resection under YELLOW 560 nm surgical microscope filter. We retrospectively analyzed the clinical characters, microsurgery procedure, extent of resection, pathology of MGs, progression-free survival (PFS), and overall survival (OS). Results. Thirty-eight patients had MGs (10 WHO grade III, 28 WHO grade IV). With YELLOW 560 nm surgical microscope filter combined with neuronavigation, sodium fluorescein-guided gross total resection (GTR) was achieved in 35 (92.1%) patients and subtotal resection in 3 (7.69%). The sensitivity and specificity of FL were 94.4% and 88.6% regardless of radiographic localization. Intraoperatively, 10 biopsies (10/28 FL[+]) showed “low” or “high” fluorescence in non-contrast-enhancement region and are also confirmed by pathology. Our data showed 6-month PFS of 92.3% and median survival of 11 months. Conclusion. FL-guided resection of MGs under the YELLOW 560 nm surgical microscope filter combined with neuronavigation was safe and effective, especially in non-contrast-MRI regions. It is feasible for improving the extent of resection in MGs especially during emergency cases.

NCOG-33. GROWTH DYNAMICS OF INCIDENTAL MENINGIOMAS - A 10-YEAR PROSPECTIVE STUDY

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi159-vi159
Author(s):  
Torbjørn Austveg Strømsnes ◽  
Morten Lund-Johansen ◽  
Geir Olve Skeie ◽  
Bente Sandvei Skeie
Keyword(s):  
Growth Rate ◽  
Tumour Growth ◽  
Growth Dynamics ◽  
Progression Free Survival ◽  
Early Observation ◽  
Active Monitoring ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
Observation Period

Abstract There is no consensus for the management of incidental meningiomas. To evaluate the natural history, we assessed tumour growth dynamics during 10 years of active monitoring of 62 patients (45 female and mean age 63.9) harbouring 68 tumours. Radiological and clinical data was obtained was obtained biannually for two years, then annually the following eight. Thirty-six patients (38 tumours) were referred to treatment and/or died of unrelated causes (n=5) within 5 years. The remaining were monitored for up to 10 years. Mean overall survival was at 128 months (95% CI: 118.8-136.7). Median progression free survival was 34 months (95% CI: 14.7-53.3). Median time for growth requiring intervention was 46 months (95% CI: 23.5-68.5). All tumours with self-limiting growth at 5 years (57.9 %) were still stable or reducing in size at 10 years. Mean growth rate decreased from 0.27 cm3/year (95% CI: 0.10-0.43) during the early observation period (0-5 years) to 0.09 cm3/year (95% CI: -0.02-0.21) in the late observation period. No tumours were referred to treatment during the late observation period. Two patients, both with verified WHO2 grade meningiomas succumbed to the disease, seven and eight years after diagnosis. No other patients developed symptoms and none other of the 18 total mortalities were meningioma related. Most clinical and radiological events occur within 5 years after diagnosis. Our findings suggests that if tumour growth slows down during the first 5 years of monitoring, this trend will continue. Clinical follow-up should be sufficient when a self-limiting growth pattern has been established.

Pazopanib in the advanced and rare subtypes of soft tissue sarcoma: Russian Sarcoma Group study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e23528-e23528
Author(s):  
Anastasia Alekseevna Tararykova ◽  
Beniamin Bokhyan ◽  
Andrey A. Konev ◽  
Polina A. Falkina ◽  
Zaur Yu. Kumekhov ◽  
...  
Keyword(s):  
Soft Tissues ◽  
Clear Cell ◽  
Soft Part ◽  
Progression Free Survival ◽  
Myxoid Liposarcoma ◽  
Clear Cell Sarcoma ◽  
Primary Tumors ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
Ewing Tumors

e23528 Background: Sarcoma is a heterogeneous group of tumors that arise from connective tissue. The most frequent localizations of primary tumors are soft tissues and bones of the extremities, and the lungs is the most common localization of metastases. Pazopanib is an antineoplastic agent, multi-kinase inhibitor that retards angiogenesis in tumor tissues and has been shown to be effective in the treatment of patients with advanced sarcoma. Median progression-free survival was 4,6 months (95% CI 3,7–4,8) for pazopanib compared with 1,6 months (0,9–1,8) for placebo in the PALETTE clinical trial. This study designed to detect epidemiology data as well as the pazopanib efficiency for rare sarcoma subtypes. Methods: We collected data from 109 cases with 20 different sarcoma histotypes and 15 localizations, at N.N. Blokhin National Medical Research Center of Oncology from 2018 till 2020. Disease was histologically confirmed by a sarcoma pathologist. The average age of patients was 47.8 years and the women and men ratio was about 2:1. Patients received pazopanib 800 mg once daily and passed control examinations every 2 or 3 months (CT/MRI). Treatment response was assessed by RECIST criteria. Results: The most frequent localizations of primary tumors were the soft tissues of the extremities (39.6%), the uterus (16.9%) and the retroperitoneum (13.2%). The main histological subtypes were leiomyosarcoma (33.6%) and synovial sarcoma (14.9%). There were also included such types like a embryonal rhabdomyosarcoma, chondrosarcoma, Ewing tumors, EHE, alveolar soft part sarcoma, PEComa, clear cell sarcoma, adamantinoma, solitary fibrous tumor, epithelioid sarcoma and myxoid liposarcoma. The majority of patients (61%) received more than 2 of therapy. The average duration of therapy was 7.5 months. Best tumor response by RECIST was as follows: complete response 0 (0%), partial response 2 (2%), stable disease 81 (88,3%), progression disease 25 (27,3%) cases. Median progression-free survival was 8 months (95% CI 6,7-9,2) for pazopanib. Median overall survival was not reached. Overall pazopanib was well tolerated, except one case with SAE. Conclusions: In this study we observed pazopanib efficiency in a rare for pazopanib sarcoma subtypes such as myxoid liposarcoma (1 PR), PEComa, adamantinoma, embryonal rhabdomyosarcoma, malignant peripheral nerve sheath tumor and Ewing tumors. Also our study confirms pazopanib long-term disease control in alveolar soft part sarcoma, clear cell sarcoma, leiomyosarcoma, synovial sarcoma and undifferentiated pleomorphic sarcoma which explains median PFS 8 months.

Chemotherapy dose intensity correlates strongly with response, median survival, and median progression-free survival in metastatic neuroblastoma.

1991 ◽  
Vol 9 (6) ◽  
pp. 1050-1058 ◽  
Author(s):  
N V Cheung ◽  
G Heller
Keyword(s):  
Median Survival ◽  
Stage Iv ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Dose Intensification ◽  
End Points ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
Major Response ◽  
Chemotherapy Dose

We examined the efficacy of five commonly used drugs, teniposide (VM26), cisplatin (CDDP), cyclophosphamide (CPM), doxorubicin (DOXO), and vincristine (VCR) in a retrospective analysis of 44 clinical trials of induction chemotherapy for stage IV neuroblastoma patients newly diagnosed at older than 1 year of age. Dose intensity (DI) of each drug was calculated as milligrams per square meter per week. Linear regression analyses showed that the Dls of VM26 and CDDP had the greatest influence on clinical outcomes (ie, proportion of major response, median survival, and median progression-free survival [PFS]), while those of CPM and DOXO were less significant. VCR had no influence on the three clinical end points. Although many protocols extended treatment to more than 1 year, none of these end points correlated positively with the duration of therapy. Twenty-one weeks appeared adequate for achieving superior response, median survival, and median PFS. These results suggest that maximal dose intensification of selective drugs over a short duration may improve the outcome of patients with poor-risk neuroblastoma.

Comparison of Standard and CA-125 Response Criteria in Patients With Epithelial Ovarian Cancer Treated With Platinum or Paclitaxel

1999 ◽  
Vol 17 (2) ◽  
pp. 501-501 ◽  
Author(s):  
John A. Bridgewater ◽  
Ann E. Nelstrop ◽  
Gordon J.S. Rustin ◽  
Martin E. Gore ◽  
William P. McGuire ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Stable Disease ◽  
Progression Free Survival ◽  
Response Rates ◽  
Response Criteria ◽  
Ca 125 ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
Standard Response

PURPOSE: To assess CA-125 as a measure of response in patients treated with paclitaxel. PATIENTS AND METHODS: One hundred forty-four patients treated with paclitaxel derived from four different trials and 625 patients treated with platinum from two trials were analyzed using precisely defined 50% and 75% reductions in CA-125. The standard and CA-125 response rates to paclitaxel and platinum were compared. In addition, we analyzed individual patient groups in which there was a difference in response according to the two response criteria. RESULTS: Patients with stable disease as determined by standard criteria who were treated with platinum and responded according to CA-125 criteria have an improved median progression-free survival compared with patients with stable disease who did not respond according to CA-125 criteria (10.6 v 4.8 months; P < .001). Standard and CA-125 response rates for patients treated with platinum (58.93% v 61.31%, respectively) and paclitaxel (30.65% v 31.67%, respectively) were very similar, as were rates of false-positive prediction of response by CA-125 (platinum 2.2% and paclitaxel 2.9%). Responders to paclitaxel had a significantly improved progression-free survival compared with nonresponders by both standard criteria (median progression-free survival, 6.8 v 2.5 months; P < .001) and CA-125 criteria (median progression-free survival, 6.8 v 3.4 months; P < .001). CONCLUSION: For assessing activity of therapy for ovarian cancer, these data show that precise 50% or 75% CA-125 response criteria are as sensitive as standard response criteria. We propose that they may be used as a measure of response in lieu of or in addition to standard response criteria in clinical trials involving epithelial ovarian cancer. Sensitivity is maintained whether patients are treated with platinum or paclitaxel.

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