Cancer Treatment Today » Brain Cancers

Zolinza for maintenance in glioblastoma

M Levin, MD — Mon, 13 May 2013 12:40:37 +0000

With the advent of biologic therapies, many new avenues to approach recalcitrant and difficult diseases have emerged. Once such cancer is the brain cancer glioblastoma(GBM). It is tempting to use Zolinza(vorinostate) for maintenance after attaining a remission of glioblastoma, because this is a disease that almost always comes back.

Unfortunately, there is as of yet no literature supporting the use of Zolnza for maintenance for gliolastoma. A recent study for recurrent disease by Galanis et al concluded that vorinostat monotherapy is well tolerated in patients with recurrent GBM and has modest single-agent activity. Histone acetylation analysis and RNA expression profiling, sophisticated wyas to look at what this drug is doing to the cancer cells, indicate that vorinostat in this dose and schedule affects target pathways in GBM. Additional testing of vorinostat in combination regimens is warranted.

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Chemo with vincristine, carboplatin and Temodar

M Levin, MD — Fri, 01 Feb 2013 19:57:36 +0000

Low grade astrocytoma occurrs in adults and children but is more commonly a pediatric disease. Radiotherapy is relatively contraindicated in children because it stunts their intellectual growth. Chemotherapy may be used in young children to avoid or to delay radiotherapy because of its potential neurologic sequelae. To date, the most active chemotherapy regimen for these tumors is carboplatin and vincristine. These agents show objective response rates of 50-80% and produce prolonged stable disease. A COG study showed the procarbazine and topotecan to be effective. Another COG study used carboplatin, vincristine, and temozolomide” but it was only a pilot study. The author’s conclusion was: “It is feasible to deliver cycles of vincristine and carboplatin alternating with temozolomide over a prolonged period of time with tolerable side effects. Preliminary data suggests that this combination is at least as effective as previous regimens in controlling disease progression. Further follow up is necessary to assess the efficacy of this regimen”.

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What is available for metastatic and aggressive meningioma

M Levin, MD — Wed, 19 Dec 2012 15:26:52 +0000

Most meningiomas are slow and benign, but a small subset can be aggressive and ahs agressive pathological features. In a 2008 review of the aggressive types, atypical and anaplastic-meningiomas, the mean overall survival for atypical meningiomas was found to be 11.9 years vs. 3.3 years for anaplastic meningiomas. Meningiomas often depend and blood vessels and and it is reasonable to consider anti blood vessel therapy for meningioma. In particular, malignant meningiomas produce high levels of vascular endothelial growth factor (VEGF) and it would make sense that Avastin should be effective, because it blocks this factor. However, agressive and anaplastic meningiomas are rare and there is little known about what works and what does not work for it. Temodar appears ineffective for refractory meningioma, but hydroxyurea is more promising.

Angiogenesis inhibitors, progestins, agents that target fundamental cell signaling pathways, somatostatin analogues, and a variety of other molecular treatments are being investigated.

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Thalidomide for glioblastoma

M Levin, MD — Thu, 06 Dec 2012 09:32:23 +0000

Glioblastoma Multiforme is a difficult to treat disease but also a disease in which significant progress has been achieved. One drug that has been extensivly studied is thalidomide. An early small study showed a 5% partial response and 42% stable disease. The median survival was 31 weeks and the 1-year survival was 35%. Patients who had a partial response or stable disease appeared to have benefitted.

It appears that thalidomide has some activity as a single agent and that it can be increased by combining it with toher drugs. One combination that has demonstrated activity is thalidomide and temozolamide and combining thalidomide and irinotecan is also promising. A number of new drugs is in trials with thalidomide.

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How often to scan the brain after radiosurgery

M Levin, MD — Thu, 22 Nov 2012 15:25:50 +0000

How to follow a patient with brain mets after radiosurgery is becoming a more and more common question becasue treatments that control cancer in the rest of the boady are getting to be more and more effective and patients are living longer before cancer comes back in the brain or in the body. One does not want to overmonitor but also not to miss metastses when they come back. Many patietns remain disease free for many months even years after radiosurgery of the brain. For example, one study reported a median time of 8.8 months to new metastasis becoming visible after radiosurgery. Patients with 3 or more brain metasttses and cancers other than NSCLC were more likely to have future metastasis. Based on these facts, there was a published recommendation for close surveillance with a 3-month interval between magnetic resonance imaging (MRI), in order to identify new metastasis early enough to start treatment. However, much is not known about this. Clearly, more frequent imaigng is warranted soon after radiosurgery and less frequenlty as time goes on. As the most sensitive tests, MRI is the preferred surveillance tool, even though newer methods, such as spectroscopy, diffusion-weighted imaging, and perfusion-weighted imaging are coming to the fore.

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Irinotecan for brain metastases of lung and breast cancer

M Levin, MD — Fri, 09 Nov 2012 15:38:40 +0000

Because irinotecan penetrates the brain-blood barrier and has an effect in primary brain cancer, there is some interest in using it for brain metastasis, especially for lung cancer and breast cancer. Most studies of irinotecan had been for brain mets of small(SCLC) and non-small cell lung cancer(NSMCLC) and not breast cancer and have had mixed results. One study enrolled several different cancer types and reported complete responses with irinotecan-based chemotherapy for brain metastases in three patients with SCLC, parotid cancer, and esophageal adenocarcinoma. The combination of cisplatin, ifosfamide and irinotecan in treatment-naive patients with NSCLC led to a response rate in the brain of 50%. A study of temozolomide (200 mg/m²) on days 1 to 5 and irinotecan (200 mg/m²) on days 1 to 5 every 4 weeks in previously untreated patients with NSCLC brain metastases reported no responses.

There are several ongoing studies for lung cancer. For breast cancer, there is also a study: Irinotecan and Temozolomide in Treating Patients With Breast Cancer Who Have Received Previous Treatment for Brain Metastases, NCT00617539.

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Ganglioglioma

M Levin, MD — Fri, 12 Oct 2012 21:34:24 +0000

Gangliogliomas are rare pediatric brain tumors that are fortunately associated with a high rate of cure. Only about 10% behave aggessively. Because of their rarity, no prospective studies have been performed regarding gangliogliomas. Data suggest a historic 20-year survival rate of approximately 80 percent. According to a recent review of four types of treatment complete removal should be performed whenever safely possible and does not require postoperative irradiation. If resection is partail, radiation therapy improves local control of both low-grade and high-grade tumors and, thus, should be considered seriously. Temodar has only been used in a few cases.

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How to dose Temodar after Glioblastoma surgery

M Levin, MD — Mon, 03 Sep 2012 22:51:24 +0000

Chemoradiation after resection is well established for glioblastoma. Three randomized studies,have all showed a benefit for it. TEMODAR® (temozolomide) is FDA indicated for the treatment of adult patients with newly diagnosed glioblastoma multiforme concomitantly with radiotherapy and then as maintenance treatment. One way to dose Temodar is with the Stupp protocol: Temodar 75 mg/m2 for 42 days with radiation. This is the dose and schedule in the Prescribing Information. NCCN also recommends combined chemoradiation.

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Temodar for Glioblastoma: Making a difference

M Levin, MD — Fri, 24 Aug 2012 19:26:22 +0000

Glioblastoma is a disease for which there were few options available until recently. The past several years brought several new potentially promising. Temozolomide (brand names Temodar and Temodal) is an oral alkylating drug. It is FDA indicated is indicated for the treatment of adult patients with newly diagnosed glioblastoma multiforme concomitantly with radiotherapy and then as maintenance treatment. TEMODAR is indicated for the treatment of adult patients with refractory anaplastic astrocytoma (an aggressive brain tumor, also known as glioblastoma multiforme) for patients who have experienced disease progression on a drug regimen containing nitrosourea and procarbazine.

Prior to this approval, only BCNU was approved for adjuvant therapy but, because of its significant toxicity, it was not widely used.

There is strong support for its use in oligodendoglioma, replacing the older (and less well-tolerated) PCV (Procarbazine-Lomustine-Vincristine) regimen. It is also supported off-label for melanoma.

The use of Temodar for glioblastoma has impacted on the overall prognosis. Data from the Surveillance, Epidemiology, and End Results (SEER) Program was analyzed to compare survival of adult glioblastoma patients diagnosed from 2000-2003 to patients diagnosed from 2005-2008, in order to evaluate pre-temozolomide and post-temozolomide periods. The Kaplan-Meier method and Cox proportional hazards models were used. 6,673 patients with glioblastoma diagnosed from 2000-2003 and 7,259 patients diagnosed from 2005-2008 were identified. Median survival times of all patients diagnosed in the 2000-2003 and 2005-2008 periods were 8.1 and 9.7 months, respectively. Amongst patients treated with surgery and a radiation-containing regimen, median survival was 12.0 months in 2000-2003 and 14.2 months in 2005-2008. In the temozolomide era, median survival times ranged from a high of 31.9 months in patients age 20-29 to a low of 5.6 months in patients age 80 and older. The survival of patients with newly diagnosed glioblastoma improved from 2000-2003 to 2005-2008, likely due to temozolomide use. However, median survival time after glioblastoma diagnosis in the SEER population remains well under one year, largely driven by poor prognosis in elderly patients.

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PET for glioblastoma

M Levin, MD — Fri, 24 Aug 2012 18:03:47 +0000

PET is more and more frequently used to visualize brain cancers. However, PET is not medically appropriate to follow glioblastoma because it not supported by credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community. PET for brain cancer is not included in the NCCN guidelines and CMS does not cover PET for this diagnosis. Occasionally, PET can provide information to differentiate tumor necrosis from tumor progression. Tumor necrosis is when a cancer dies after being treated. The sensitivity of PET for differentiating necrosis and tumor progression is 80%–90% and the specificity is 50%–90%. Causes of false-negative PET results include recent radiation therapy, low grade, and small tumor volume. PET may be false positive in nonmalignant inflammatory processes and subclinical seizure activity. The question of hypermetabolic foci of radiation injury as a cause of false-positive scans requires further investigation. Other issues requiring further study are the optimal timing of PET after radiation and chemotherapy and the accuracy of PET in tumors other than high-grade gliomas.

A 2010 guideline by Laperrier says: “Positron emission tomography (PET) is not recommended for the determination of diagnosis or grading in gliomas. A recommendation cannot be made for or against the use of PET or positron emission tomography/computed tomography (PET/CT) in the assessment of patients with recurrent gliomas because of insufficient evidence. Positron emission tomography (PET) is not recommended for the determination of diagnosis or grading in gliomas. A recommendation cannot be made for or against the use of PET for the assessment of treatment response in gliomas because of insufficient evidence. A recommendation cannot be made for or against the use of PET or positron emission tomography/computed tomography (PET/CT) in the assessment of patients with recurrent gliomas because of insufficient evidence. Positron emission tomography (PET) is not recommended for the determination of diagnosis or grading in gliomas. A recommendation cannot be made for or against the use of PET for the assessment of treatment response in gliomas because of insufficient evidence. A recommendation cannot be made for or against the use of PET or positron emission tomography/computed tomography (PET/CT) in the assessment of patients with recurrent gliomas because of insufficient evidence.”
It is not clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the condition in question as per literature and guidelines

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