Radiation Therapy Combined With Chemotherapy in Treating Patients With Anaplastic Astrocytoma or Mixed Gliomas by Lorena Godinez https://padlet.com/lg694/jno5bp4ys4xoqlmk Lorena Godinez en-us 2022-04-14 18:01:30 UTC 2022-04-15 23:27:40 UTC hello@padlet.com Abstract lg694 https://padlet.com/lg694/jno5bp4ys4xoqlmk/wish/2144192060 Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy, such as temozolomide, carmustine, and lomustine, use different ways to stop tumor cells from dividing so they stop growing or die. Combining radiation therapy with chemotherapy may kill more tumor cells. This study's purpose is to determine the safety and toxicity of carmustine (BCNU) and temozolomide (TMZ) with radiotherapy (RT) in newly diagnosed anaplastic astrocytoma or mixed gliomas.

Two hundred and thirty participants were enrolled in a two-phase study. Phase I contained 30 patients and Phase III had 454 patients (227 per treatment arm). This study focuses on the phase I results. A total of 15 and 14 patients were enrolled in the two pilot arms for Phase I. Because of hematologic and pulmonary toxicities, dose reductions by the second cycle of therapy occurred in >70% of the patients in Arm 1 and >50% in Arm 2 despite a reduction in the carmustine dose 

]]> 2022-04-14 17:56:25 UTC https://padlet.com/lg694/jno5bp4ys4xoqlmk/wish/2144192060 Introduction lg694 https://padlet.com/lg694/jno5bp4ys4xoqlmk/wish/2145139431 Astrocytomas are the most common type of brain tumor in both adults and children. They are a type of brain tumor called glioma. Gliomas can be put into groups according to how quickly they are likely to grow. There are 4 groups, called grades 1 to 4. Grade 4 astrocytomas are also called glioblastoma. Astrocytomas develop from a type of glial cells called astrocytes. Astrocytes are star-shaped cells. They support the nerve cells in the brain. Astrocytomas can be low grade (slow-growing) or high grade (fast-growing). There are 4 main types:

·         Low-grade
o   pilocytic astrocytoma (grade 1)
o   diffuse astrocytoma (grade 2). The average survival time after surgery is 6 - 8 years. More than 40% of people live more than 10 years.
 
·         High grade
o   anaplastic astrocytoma (grade 3). About 27% of people diagnosed with high-grade astrocytoma live for five years or more.
o   glioblastoma (grade 4). The average survival time is 12-18 months - only 25% of glioblastoma patients survive more than one year, and only 5% of patients survive more than five years.

Surgery is the main treatment for high-grade astrocytomas. After surgery patients receive radiotherapy and chemotherapy, usually using a nitrosourea. Temozolomide (TMZ) was chosen for this study because of the encouraging clinical reports of antitumor activity  

The main goal of this study is to compare the overall survival and time to tumor progression in patients with anaplastic astrocytoma or mixed gliomas treated with radiotherapy (RT) combined with temozolomide (TMZ) vs carmustine (BCNU) or lomustine (CCNU). Compare the relative toxic effects of these regimens in these patients. Correlate molecular analyses with overall survival and time to tumor progression in patients treated with these regimens.

 

]]> 2022-04-15 19:44:38 UTC https://padlet.com/lg694/jno5bp4ys4xoqlmk/wish/2145139431 Methods lg694 https://padlet.com/lg694/jno5bp4ys4xoqlmk/wish/2145163118 Patients >18 years old with anaplastic astrocytoma, a Karnofsky performance status score of > or =60, and adequate pulmonary function were eligible. The Karnofsky Performance Status Scale determines the ability of a patient to tolerate chemotherapies. Standard RT was started within 5 weeks of diagnosis. In both arms, 150 mg/m(2) of TMZ was given on Days 1-5 of RT. In Arm 1, 200 mg/m(2) of carmustine was given on Day 1 of RT. In Arm 2, 150 mg/m(2) of carmustine was given on Day 5 of RT. After RT, TMZ and carmustine were repeated for a total of six cycles.


]]> 2022-04-15 20:40:11 UTC https://padlet.com/lg694/jno5bp4ys4xoqlmk/wish/2145163118 Results lg694 https://padlet.com/lg694/jno5bp4ys4xoqlmk/wish/2145177630 First arm results:

·  1 patient stopped all therapy due to toxicity
·  2 patients stopped carmustine,
·  1 patient stopped TMZ
·  Two late Grade 3 and one Grade 4 infections occurred

The first arm was shown to be poorly tolerated. 

Second arm results:

·  1 patient's condition progressed before the evaluation of toxicity was performed.
·  Two patients stopped carmustine after the first cycle because of pulmonary toxicity.

In both arms, a significant number of patients (70%) required a dose reduction by the second cycle because of toxicity.  In the second arm, Grade 3 pulmonary toxicity was not seen and only 4 (33%) of 12 patients developed Grade 4 bone marrow toxicity.

 

]]> 2022-04-15 21:15:51 UTC https://padlet.com/lg694/jno5bp4ys4xoqlmk/wish/2145177630 Results lg694 https://padlet.com/lg694/jno5bp4ys4xoqlmk/wish/2145177803 2022-04-15 21:16:20 UTC https://padlet.com/lg694/jno5bp4ys4xoqlmk/wish/2145177803 Discussion lg694 https://padlet.com/lg694/jno5bp4ys4xoqlmk/wish/2145222172 When this study was performed TMZ was shown to promising treatment for recurrent malignant glioma. Preclinical data also demonstrated a synergistic effect of the combination of carmustine and TMZ but both agents have overlapping toxicities. ). Because of the limited data on the toxicity of the combination of these agents and the lack of information on the safety and tolerability of the combination with RT, these pilot arms were conducted by the Radiation Therapy Oncology Group before proceeding with a randomized study that would have incorporated the combination

From the phase I study, researchers concluded that the combination of these drugs with RT leads to high toxicities. However, the significant number of low toxicity seen in arm 2 in the first cycle precluded continuing the Phase III study using the same drug administration schedule to either single-agent carmustine or TMZ with RT.

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