Carboplatin and vincristine for recurrent and newly diagnosed low-grade gliomas of childhood.

1993 ◽  
Vol 11 (5) ◽  
pp. 850-856 ◽  
Author(s):  
R J Packer ◽  
B Lange ◽  
J Ater ◽  
H S Nicholson ◽  
J Allen ◽  
...  
Keyword(s):  
Tumor Size ◽  
Maintenance Treatment ◽  
Objective Response ◽  
Drug Regimen ◽  
Response To Treatment ◽  
Hematologic Toxicity ◽  
Low Grade ◽  
Newly Diagnosed ◽  
Low Grade Gliomas ◽  
Induction Cycle

PURPOSE This study investigates the response rate to and toxicity of carboplatin and vincristine in children with recurrent low-grade gliomas (LGGs) or patients younger than 60 months with newly diagnosed LGGs. PATIENTS AND METHODS Twenty-three children with recurrent and 37 children with newly diagnosed LGGs were treated with a 10-week induction cycle of carboplatin and vincristine, followed by maintenance treatment with the same drugs. Patients were evaluated for response to treatment and toxicity. RESULTS Twelve of 23 (52% +/- 10%; 95% confidence interval [CI], 0.32 to 0.72) assessable children with recurrent disease had an objective response to treatment, which included a greater than 50% reduction in tumor size in seven of 23 (30% +/- 10%; 95% CI, 0.10 to 0.50). Twenty-three of 37 (62% +/- .08; 95% CI, 0.46 to 0.78) of newly diagnosed patients had an objective response, 16 of 37 (43% +/- 0.08%; 95% CI, 0.27 to 0.59) with greater than 50% reduction in tumor size. The majority of those with an objective response had diencephalic tumors (n = 29), but children with thalamic (n = 2), cortical (n = 1), and brain stem (n = 2) LGGs also responded to treatment. Of the 35 patients with objective response to treatment, the maximum response was seen in 25 after completion of induction and in the remaining 10 after two to six cycles of maintenance treatment. Forty-nine of 53 (92% +/- .04%) patients who were stable or improved after induction remain without progressive disease (PD). Hematologic toxicity was common, but resulted in cessation of therapy in only one patient. Six children have been removed from the study because of allergic reactions, which were considered to be carboplatin-associated. CONCLUSION Carboplatin and vincristine have activity in children with recurrent and newly diagnosed progressive LGGs. Objective responses to treatment after chemotherapy can be seen. This drug regimen is relatively well tolerated, and further studies are indicated to define the role of this combination of drugs in children with newly diagnosed LGGs.

scholarly journals Carboplatin and vincristine chemotherapy for children with newly diagnosed progressive low-grade gliomas

1997 ◽  
Vol 2 (3) ◽  
pp. E1
Author(s):  
Roger J. Packer ◽  
Joanne Ater ◽  
Jeffrey Allen ◽  
Peter Phillips ◽  
Russell Geyer ◽  
...  
Keyword(s):  
Objective Response ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Response To Treatment ◽  
Low Grade ◽  
Significant Prognostic Factor ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Low Grade Gliomas ◽  
Response To Chemotherapy

The optimum treatment of nonresectable low-grade gliomas of childhood remains undecided. There has been increased interest in the use of chemotherapy for young children, but little information concerning the long-term efficacy of such treatment. Seventy-eight children with a mean age of 3 years (range 3 months-16 years) who had newly diagnosed, progressive low-grade gliomas were treated with combined carboplatin and vincristine chemotherapy. The patients were followed for a median of 30 months from diagnosis, with 31 patients followed for more than 3 years. Fifty-eight children had diencephalic tumors, 12 had brainstem gliomas, and three had diffuse leptomeningeal gliomas. Forty-four (56%) of 78 patients showed an objective response to treatment. Progression-free survival rates were 75 ± 6% at 2 years and 68 ± 7% at 3 years. There was no statistical difference in progression-free survival rates between children with neurofibromatosis Type 1 and those without the disease (2-year, progression-free survival 79 ± 11% vs. 75 ± 6%, respectively). The histological subtype of the tumor, its location, and its maximum response to chemotherapy did not have an impact on the duration of disease control. The only significant prognostic factor was age: children 5 years old or younger at the time of treatment had a 3-year progression-free survival rate of 74 ± 7% compared with a rate of 39 ± 21% in older children (p < 0.01). Treatment with carboplatin and vincristine is effective, especially in younger children, in controlling newly diagnosed progressive low-grade gliomas.

Carboplatin and vincristine chemotherapy for children with newly diagnosed progressive low-grade gliomas

1997 ◽  
Vol 86 (5) ◽  
pp. 747-754 ◽  
Author(s):  
Roger J. Packer ◽  
Joanne Ater ◽  
Jeffrey Allen ◽  
Peter Phillips ◽  
Russell Geyer ◽  
...  
Keyword(s):  
Objective Response ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Response To Treatment ◽  
Low Grade ◽  
Significant Prognostic Factor ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Low Grade Gliomas ◽  
Response To Chemotherapy

✓ The optimum treatment of nonresectable low-grade gliomas of childhood remains undecided. There has been increased interest in the use of chemotherapy for young children, but little information concerning the long-term efficacy of such treatment. Seventy-eight children with a mean age of 3 years (range 3 months—16 years) who had newly diagnosed, progressive low-grade gliomas were treated with combined carboplatin and vincristine chemotherapy. The patients were followed for a median of 30 months from diagnosis, with 31 patients followed for more than 3 years. Fifty-eight children had diencephalic tumors, 12 had brainstem gliomas, and three had diffuse leptomeningeal gliomas. Forty-four (56%) of 78 patients showed an objective response to treatment. Progression-free survival rates were 75 ± 6% at 2 years and 68 ± 7% at 3 years. There was no statistical difference in progression-free survival rates between children with neurofibromatosis Type 1 and those without the disease (2-year, progression-free survival 79 ± 11% vs. 75 ± 6%, respectively). The histological subtype of the tumor, its location, and its maximum response to chemotherapy did not have an impact on the duration of disease control. The only significant prognostic factor was age: children 5 years old or younger at the time of treatment had a 3-year progression-free survival rate of 74 ± 7% compared with a rate of 39 ± 21% in older children (p < 0.01). Treatment with carboplatin and vincristine is effective, especially in younger children, in controlling newly diagnosed progressive low-grade gliomas.

Temozolomide Low-dose Chemotherapy in Newly Diagnosed Low-grade Gliomas: Activity, Safety, and Long-term Follow-up

2016 ◽  
Vol 103 (3) ◽  
pp. 255-260 ◽  
Author(s):  
Veronica Villani ◽  
Roberta Merola ◽  
Antonello Vidiri ◽  
Alessandra Fabi ◽  
Mariantonia Carosi ◽  
...  
Keyword(s):  
Clinical Benefit ◽  
Low Dose ◽  
Karnofsky Performance Status ◽  
Objective Response ◽  
High Rate ◽  
Low Grade ◽  
Newly Diagnosed ◽  
Minor Response ◽  
Low Grade Gliomas

Purpose To explore the efficacy and toxicity of an extended schedule of temozolomide (50 mg/mq 1 week on/1 week off) in a population of newly diagnosed low-grade gliomas (LGG). Methods Primary endpoints were progression-free survival (PFS) at 12 and 24 months and response rate evaluated with Response Assessment in Neuro-Oncology Criteria. Secondary endpoints were clinical benefit (reduction of seizures frequency), reduction of steroid, and modifications of Karnofsky Performance Status. Results From 2006 to 2009, we enrolled 14 consecutive patients with newly diagnosed LGG: 8 grade II astrocytomas, 2 oligodendroglioma, and 4 oligo-astrocytoma. Temozolomide was administered for 18 cycles (mean) per patient (range 3-24 cycles). In 57.5% (n = 8), we observed stable disease, 28.5% (n = 4) presented a minor response, and 14% (n = 2) showed progression. Five patients presented early progression during the first year of treatment and the study was stopped. A relevant clinical benefit was observed in 85% of patients (seizure control). After 6 years of follow-up, only 4 patients died. Prolonged PFS was associated with 1p-19q codeletion over 1p-19q intact (35 vs 4 months; p<0.04) and IDH1 mutation over IDH1 wild-type (36 vs 6 months; p<0.009). Conclusions The study was interrupted for the high rate of progression observed in the first 14 patients enrolled. However, our results show that an extended low dose of temozolomide presents interesting activity with objective response and clinical benefit, but does not seem to prevent progression in patients presenting unfavorable molecular prognostic factors.

Sequential VAD (Vincristine, Adriamycin, Dexamethasone) and VTD (VELCADE®, Thalidomide, Dexamethasone) Induction Followed by High-Dose Therapy with Autologous Stem Cell Transplantation and Maintenance Treatment with VELCADE for Newly Diagnosed Multiple Myeloma: Interim Results of Phase II Trial.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 952-952 ◽  
Author(s):  
Sung-Soo Yoon ◽  
Hye Jin Kim ◽  
Dong Soon Lee ◽  
Hyeon Seok Eom ◽  
Jun Ho Jang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Maintenance Treatment ◽  
Response Rate ◽  
High Dose ◽  
Hematologic Toxicity ◽  
Newly Diagnosed

Abstract Introduction Effective reduction of myeloma before autologous stem cell transplantation (ASCT) prolongs survival in multiple myeloma patients. Recently, incorporation of novel agents resulted in improved response rate and reduced side effect in newly diagnosed multiple myeloma. Method: Patients are planned to receive 2 cycles of VAD (vincristine 0.4mg D1-4, adriamycin 9mg/m2 D1-4, dexamethasone 40mg D1-4, 9–12 every 3 weeks), and VTD (bortezomib 1.3mg/m2 D1, 4, 8, 11, thalidomide 100mg daily, dexamethasone 40mg D1-4, 9–12 every 3 weeks). High dose melphalan (200mg/m2) is used as a conditioning regimen for ASCT. Bortezomib (1.3mg/m2) as a maintenance treatment is administered weekly x 4 times every 6 weeks for 4 cycles after ASCT. Response was assessed by EBMT criteria, with additional category of nCR. Adverse events were graded by the NCI-CTCAE, Version 3.0. Result: At this interim analysis, 60 patients have been entered into the ongoing trial, and efficacy could be assessed in 53 patients. After 2 cycles of VAD, response rate was 70%. After VTD, two patients showed further improvement with additional CR, and an overall response was 97% with 14% CR. Especially, patients with poor prognostic cytogenetics (n=6) all responded after VTD. So far, autologous stem cells were successfully collected in all 28 patients with a median CD34+ count of 7.8 x 106/kg (range, 2.17–44.7 x 106/kg). In 24 patients who underwent autologous stem cell transplantation, five patients gained additional CR. There was no progression in patients completed bortezomib maintenance (n=9, CR 77%). The median follow-up duration was 6 months, median time to response was 1.4 months, and median overall survival was not reached. Grade 3,4 hematologic toxicity was more frequently observed after VAD than VTD (anemia 15.8%, 4.6%, neutropenia 7.9%, 3.5%), and incidence of grade 2,3 peripheral neuropathy was low (VAD 3.5%, VTD 7%). Conclusion: Sequential VAD and VTD induction therapy in newly diagnosed multiple myeloma was highly effective, even in patients with poor prognostic cytogenetics, and did not prejudice stem cell collection. VTD could have contributed to increased RR and minimized side effects. An updated results will be presented at the ASH meeting. *Protocol Number: KMM51-NCT00378755.

Circumferential sulcus-guided resection technique for improved outcomes of low-grade gliomas

2022 ◽  
pp. 1-11
Keyword(s):  
Extent Of Resection ◽  
Neurological Complications ◽  
Low Grade ◽  
Newly Diagnosed ◽  
Imaging Data ◽  
Volumetric Imaging ◽  
Exact Test ◽  
Low Grade Gliomas ◽  
Presenting Symptoms ◽  
Piecemeal Resection

OBJECTIVE Many neurosurgeons resect nonenhancing low-grade gliomas (LGGs) by using an inside-out piecemeal resection (PMR) technique. At the authors’ institution they have increasingly used a circumferential, perilesional, sulcus-guided resection (SGR) technique. This technique has not been well described and there are limited data on its effectiveness. The authors describe the SGR technique and assess the extent to which SGR correlates with extent of resection and neurological outcome. METHODS The authors identified all patients with newly diagnosed LGGs who underwent resection at their institution over a 22-year period. Demographics, presenting symptoms, intraoperative data, method of resection (SGR or PMR), volumetric imaging data, and postoperative outcomes were obtained. Univariate analyses used ANOVA and Fisher’s exact test. Multivariate analyses were performed using multivariate logistic regression. RESULTS Newly diagnosed LGGs were resected in 519 patients, 208 (40%) using an SGR technique and 311 (60%) using a PMR technique. The median extent of resection in the SGR group was 84%, compared with 77% in the PMR group (p = 0.019). In multivariate analysis, SGR was independently associated with a higher rate of complete (100%) resection (27% vs 18%) (OR 1.7, 95% CI 1.1–2.6; p = 0.03). SGR was also associated with a statistical trend toward lower rates of postoperative neurological complications (11% vs 16%, p = 0.09). A subset analysis of tumors located specifically in eloquent brain demonstrated SGR to be as safe as PMR. CONCLUSIONS The authors describe the SGR technique used to resect LGGs and show that SGR is independently associated with statistically significantly higher rates of complete resection, without an increase in neurological complications, than with PMR. SGR technique should be considered when resecting LGGs.

scholarly journals Genetic variants related to angiogenesis and apoptosis in patients with glioma

2018 ◽  
Vol 76 (6) ◽  
pp. 393-398
Author(s):  
Maria Clara Jessica Calastri ◽  
Nicolas Luz Toledo Ortega Rodrigues ◽  
Gabriela Hatori ◽  
Michele Lima Gregório ◽  
Camila Ive Ferreira Oliveira Brancati ◽  
...  
Keyword(s):  
Risk Factors ◽  
Genetic Variants ◽  
Medical Records ◽  
Patient Survival ◽  
Response To Treatment ◽  
Low Grade ◽  
Significance Level ◽  
Low Grade Gliomas ◽  
Homozygous Genotype ◽  
Independent Risk Factors

ABSTRACT Background Glioma, the most common primary malignant brain tumor in adults, is highly aggressive and associated with a poor prognosis. The objectives of this study were to evaluate the association of genetic polymorphisms related to angiogenesis and apoptosis with gliomas, as well as comorbidities, lifestyle, clinical profile, survival and response to treatment (temozolomide [TMZ] and radiotherapy [RT]) in patients with the disease. Methods In a total of 303 individuals, genotypes were performed by real-time PCR, and clinical data, lifestyle and comorbidities were obtained from medical records and questionnaires. The significance level was set at 5%. Results Smoking, alcohol consumption, systemic arterial hypertension, diabetes mellitus and body mass index prevailed among patients, compared to controls (p < 0.05). The heterozygous genotype rs1468727 (T/C) and the homozygous genotype rs2010963 (G/G) (p > 0.05) were observed in both groups. Lifestyle and comorbidities showed independent risk factors for the disease (p < 0.0001, p = 0.0069, p = 0.0394, respectively). Patients with low-grade gliomas had a survival rate of 80.0 ± 1.7% in three years. For the combination of TMZ+RT, survival was 78.7 ± 7.6% in 20 months, compared to TMZ only (21.9 ± 5.1%, p = 0.8711). Conclusions Genetic variants were not associated with gliomas. Specific lifestyle habits and comorbidities stood out as independent risk factors for the disease. Low-grade gliomas showed an increase in patient survival with TMZ+RT treatment.

scholarly journals Association of high‐dose radiotherapy with improved survival in patients with newly diagnosed low‐grade gliomas

Cancer ◽  
2021 ◽  
Author(s):  
Yanwei Liu ◽  
Shuai Liu ◽  
Guanzhang Li ◽  
Yanong Li ◽  
Li Chen ◽  
...  
Keyword(s):  
High Dose ◽  
Low Grade ◽  
Newly Diagnosed ◽  
Low Grade Gliomas

scholarly journals High-dose radiotherapy in newly diagnosed low-grade gliomas with nonmethylated O(6)-methylguanine-DNA methyltransferase

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Yanwei Liu ◽  
Yanong Li ◽  
Peng Wang ◽  
Li Chen ◽  
Jin Feng ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Dna Methyltransferase ◽  
Univariate Analysis ◽  
High Dose ◽  
Low Grade ◽  
Newly Diagnosed ◽  
Great Resistance ◽  
Low Grade Gliomas ◽  
Methylguanine Dna Methyltransferase ◽  
Significant Difference

Abstract Background Patients with low-grade gliomas (LGGs) harboring O6-methylguanine-DNA methyltransferase promoter nonmethylation (MGMT-non-pM) have a particularly short survival and are great resistance to chemotherapy. The objective of this study was to assess the efficacy of high-dose radiotherapy (RT) for LGGs with MGMT-non-pM. Methods 268 patients with newly diagnosed adult supratentorial LGGs from the multicenter Chinese Glioma Cooperative Group (CGCG) received postoperative RT during 2005–2018. MGMT promoter methylation analysis was conducted by pyrosequencing in all patients. Univariate and multivariate analysis were performed using the Cox regression to determine the prognostic factors for overall survival (OS) and progression-free survival (PFS). RT dose–response on MGMT status defined subtypes was analyzed. Results On univariate analysis, the following were statistically significant favorable factors for both PFS and OS: oligodendrogliomas(p = 0.002 and p = 0.005), high-dose RT (> 54 Gy) (p = 0.021 and p = 0.029) and 1p/19q codeletion (p < 0.001 and p = 0.001). On multivariate analysis, RT dose (> 54 Gy vs. ≤ 54 Gy) and IDH mutation were independently prognostic markers for OS (HR, 0.47; 95%CI, 0.22–0.98; p = 0.045; and HR, 0.44; 95%CI, 0.21–0.96; p = 0.038, respectively) and PFS (HR, 0.48; 95%CI, 0.26–0.90; p = 0.022; and HR, 0.51; 95%CI, 0.26–0.98; p = 0.044, respectively). High-dose RT was associated with longer OS (HR, 0.56; 95%CI, 0.32–0.96; p = 0.036) and PFS (HR, 0.58; 95%CI, 0.35–0.96; p = 0.033) than low-dose RT in MGMT-non-pM subtype. In contrast, no significant difference in either OS (p = 0.240) or PFS (p = 0.395) was observed with high-dose RT in the MGMT-pM subtype. Conclusions High-dose RT (> 54 Gy) is an independently protective factor for LGGs and is associated with improved survival in patients with MGMT-non-pM.

scholarly journals LGG-59. REMARKABLE OBJECTIVE RESPONSE AND FAVORABLE SURVIVAL FOR BRAF-V600E CHILDHOOD LOW-GRADE GLIOMAS TO BRAF INHIBITORS COMPARED CONVENTIONAL CHEMOTHERAPY

2018 ◽  
Vol 20 (suppl_2) ◽  
pp. i117-i117
Author(s):  
Michal Zapotocky ◽  
Scott Ryall ◽  
Kohei Fukuoka ◽  
Ana Guerreiro Stucklin ◽  
Julie Bennett ◽  
...  
Keyword(s):  
Objective Response ◽  
Braf V600e ◽  
Low Grade ◽  
Braf Inhibitors ◽  
Conventional Chemotherapy ◽  
Low Grade Gliomas

Combination Therapy with CC-5013 (Lenalidomide; Revlimid™) Plus Dexamethasone (Rev/Dex) for Newly Diagnosed Myeloma (MM).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 331-331 ◽  
Author(s):  
S. Vincent Rajkumar ◽  
Suzanne R. Hayman ◽  
Martha Q. Lacy ◽  
Angela Dispenzieri ◽  
Antje Hoering ◽  
...  
Keyword(s):  
Adverse Events ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Final Analysis ◽  
Initial Therapy ◽  
M Protein ◽  
Thrombosis Prophylaxis ◽  
Hematologic Toxicity ◽  
Newly Diagnosed ◽  
Vein Thrombosis

Abstract Background: Increasingly thalidomide (Thal) plus dexamethasone (Dex) is being used as initial therapy for multiple myeloma (MM), but there is a need to minimize non-hematologic toxicity with this regimen. CC-5013 (lenalidomide; Revlimid™) is a more potent analog of thalidomide with significantly fewer non-hematologic toxicities that has shown promising results in relapsed refractory myeloma. We report the initial results of the first phase II trial using the combination of CC-5013 plus Dex (Rev/Dex) as initial therapy for newly diagnosed MM. Methods: The trial is designed to accrue 31 eligible patients; 13 patients (pts) (11 male and 2 female) were analyzed in this interim report. Patients were enrolled between February 2004 and July 2004. CC-5013 was given orally at a dose of 25 mg daily on days 1–21 of a 28-day cycle. Dex was given orally at a dose of 40 mg daily on days 1–4, 9–12, 17–20 of each cycle. Patients also received an aspirin once daily as thrombosis prophylaxis. Response was defined as a decrease in serum monoclonal (M) protein by 50% or higher and a decrease in urine M protein by at least 90% or to a level less than 200 mg/24 hours. Responses were assessed on an intent to treat basis. Results: The median age was 61 years (range, 32–78). 8 patients (62%) had Stage III myeloma. 11 of the 13 patients achieved an objective response yielding a response rate of 85% within 1–2 months of therapy. So far 6 patients have experienced grade 3 adverse events. These include one episode each of CD4-count < 200/mm3, anemia, neutropenia, increased liver enzymes, muscle weakness, agitation, hyperglycemia, cardiac arrhythmia, pneumonitis, and colonic perforation (underlying diverticulitis and dexamethasone suspected). No deep vein thrombosis or grade 4 or higher adverse events have been observed so far. Conclusions: Rev/Dex appears active and well tolerated in the treatment of newly diagnosed MM and is a potential alternative to Thal/Dex. However, these results are preliminary and responses are still being evaluated and need to be confirmed in the final analysis of this trial. A large randomized trial using Rev/Dex as initial therapy for MM is expected to be activated by the Eastern Cooperative Oncology Group later this year.

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