Cancer Treatment Today » Glioblastoma

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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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 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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Afinitor for glioblastoma

M Levin, MD — Fri, 24 Aug 2012 13:25:45 +0000

There is evidence that the MTOR pathway plays an important role in renal cell cancer. It is also effective in neuroendocrine cancer. AFINITOR®(everolimus) is indicated for the treatment of renal cell carcinoma and progressive neuroendocrine tumors of pancreatic origin (PNET) in patients with unresectable, locally advanced or metastatic disease. The safety and effectiveness of AFINITOR® in the treatment of patients with glioblastoma has not been established.

Clinicaltrials.gov cites more than 30 studies of Afinitor in glioblastoma. Preliminary results have not been encouraging. Twenty-two patients with recurrent glioblastoma (GBM) were prospectively treated with everolimus and gefitinib, designed to test the combined inhibition of two drugs mammalian targets by both drugs as part of a larger clinical trial. The primary endpoint was radiographic response rate. Secondary endpoints included progression-free survival and correlation of molecular profiles with treatment response. 36% of patients had stable disease and 14% a partial response; however, responses were not durable and only one patient was progression-free at six months. Radiographic changes were not well characterized by conventional response criteria, and implied differential effects of therapy within the tumor and/or anti-angiogenic effects. EGFR and PTEN status did not clearly predict response to treatment. Clearly more study is in order.

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Votrient for Glioblastoma

M Levin, MD — Wed, 20 Jun 2012 19:50:05 +0000

Glioblastoma is a common brain cancer. It is currently approved for renal cell carcinoma with some activity against glioblastoma. Votrient(pazopanib) is a multi-targeted tyrosine kinase inhibitor with some activity against brain cancers. It also exhibits activity against melanoma and breast, prostate, colon, and lung cancers, although it has not yet been approved for use in those cancers. In this it is an advance over other currently available similar drugs that don’t have as a broad activity and affect one or two targets. It is in clinical trials for glioblastoma.

An encouraging phase II study in glioblastoma had been published. Single-agent pazopanib did not prolong PFS in this patient population but showed in situ biological activity as demonstrated by radiographic responses.

More research is ongoing.

It is important to know that 52% of the patients in one study reported diarrhea, although only less than 4% had grade 3 or 4 (severe) symptoms. 40% of the patients experienced an increase in blood pressure and other side effects. Careful attention to managing side effects can prevent discontinuation of therapy.

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