Month: December 2010

Everolimus for Neuroendocrine Tumors

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In the RADIANT-2 trial, Everolimus (Afinitor), an oral mTOR (mammalian Target Of Rapamycin) inhibitor was administered in combination with Octreotide LAR to patients with advanced non pancreatic neuroendocrine tumors. The control group received placebo in combination with Octreotide LAR. There was a significant improvement in the progression free survival in favor of the mTOR inhibitor given in combination with Octreotide LAR.

We now have a viable treatment option for the treatment of carcinoid tumors with symptoms.

Aggressive Melanoma in patients with CLL

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It appears that patients with a history of Chronic Lymphocytic Leukemia (CLL) are at a higher risk of developing Malignant Melanoma. If they do develop this skin cancer, they tend to have more aggressive disease than their non-CLL counterparts, with a higher mortality rate. This may be related to genetic aberrations common to both CLL and Malignant Melanoma. They include genetic aberrations of P53 gene and proto-oncogene B-Cell Lymphoma- 2 (Bcl-2).

It is therefore important that patients with CLL be closely monitored for melanoma and take the necessary sun-protective measures. Further, even when diagnosed with early stage Malignant Melanoma, these individuals may need aggressive local intervention.

Oncoprescribe Blog Prognosis in AML based on gene signature

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Outcomes in Acute Myeloid Leukemia (AML) is dependent on age, FLT3 mutations and cytogenetics, that is, until now. A study published in the JAMA this month concluded that high expression of Leukemic Stem Cell (LSC) gene expression signature was independently associated with lower remission rates following induction chemotherapy, as well as inferior relapse free, event free and overall survival in patients with normal as well as abnormal karyotypic findings and was also independent of age and FLT3 mutations.

The LSC score will soon become a very important component for risk stratification in patients with AML

Oncoprescribe Blog Identifying the Origin of Challenging Tumors

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Cancer of Unknown Primary Site (CUPS) may soon become a term of the past. With the availability of microarray technology, gene expression patterns of metastatic poorly differentiated and undifferentiated cancers can now be compared with gene expression patterns of known tissue types representing morphology of solid tumors. This in turn may help identify the site of origin of a particular  tumor.

The “Tissue of Origin”is one such test cleared by the FDA to identify the origin of a challenging tumor. It is encouraging to note that these molecular methodologies are helping both diagnose and treat cancer patients.

Oncoprescribe Blog Ovarian Cancer Screening

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Ovarian cancer is potentially curable if diagnosed at an early stage. Unfortunately only 20-25% of the patients are diagnosed with early stage disease, ie. Stage I and Stage II. Majority of the patients with ovarian cancer are diagnosed with Stage III or Stage IV disease. Screening postmenopausal women or those considered to be at high risk therefore makes perfect sense. A British study  presented at ASCO 2010, screened postmenopausal women, considered not to be at high risk,with a combination of pelvic ultrasound and CA-125. Preliminary data is very promising and screening techniques were able to diagnose ovarian cancer at an earlier stage.

It is possible that we may have an algorithm to screen for ovarian cancer, in the very near future.

Oncoprescribe Blog VEGF In Brain Tumors

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It appears that VEGF (Vascular Endothelial Growth Factor) is the main driver for low and high grade malignant gliomas. These tumors, as one would expect, also harbor high concentrations of VEGF receptors. In fact, tumor VEGF receptor concentration appears to be directly related to poor clinical outcomes. This would make perfect sense as VEGF development was based on Glioblastoma Multiforme xenograft models.

No wonder, Bevacizumab (AVASTIN), a humanized antibody targeting VEGF in combination with chemotherapy, improved response rates, progression free survival and overall survival.

Oncoprescribe Blog Prostate Cancer – Androgen Independent or Castrate Resistant

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It is not semantics anymore. Prostate Cancer is a heterogeneous disease. It appears that in patients touted to have Hormone Refractory Prostate Cancer (HRPC), the cells continue to produce androgen receptor message even in the absence of androgens. The tumor cells are therefore not androgen independent. On the contrary, they continue to  thrive, having access to androgens or androgen precursors, by various different mechanisms. It is for this reason imperative that one continue chemical castration with LHRH agonists concurrently with other lines of treatment including chemotherapy.

So the appropriate term should be Castrate Resistant Prostate Cancer rather than Androgen Independent Prostate Cancer.

Oncoprescribe Blog Pazopanib in Thyroid Cancer

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Pazopanib (Votrient) is a Tyrosine Kinase Inhibitor (TKI) that  targets Vascular Endothelial Growth Factor Receptor (VEGFR), Platelet-Derived Growth Factor Receptor (PDGFR), c-kit and Ret. This drug is presently approved by the FDA for the treatment of metastatic renal cell carcinoma. Data presented at the ASCO 2010 demonstrated impressive responses using Pazopanib (Votrient) in advanced radioiodine-refractory Follicular, Papillary and even Hurthle cell thyroid carcinomas.

This is an important step forward, in addressing this malignancy, as the benefit seen with chemotherapy is at best marginal, in the subset of patients studied. VEGF (Vascular Endothelial Growth Factor) appears to play a very important role in the pathogenesis of Thyroid Carcinomas. Learning and targeting the molecular mechanism of a malignancy is clearly the wave of the future.

Oncoprescribe Blog Vandetanib (Zactima) in Medullary Thyroid Cancer

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Medullary Thyroid Cancer accounts for about 6% of all thyroid cancers. This cancer originates from the parafollicular cells, also called C cells, of the thyroid. Calcitonin is a hormone produced by the C cells. For this reason, measuring serum calcitonin following complete resection of Medullary Thyroid Carcinoma can be helpful in diagnosing recurrent disease.

There is presently no active treatment approved by the FDA,  for the treatment of advanced Medullary Thyroid Carcinoma (MTC). A new oral Tyrosine Kinase Inhibitor (Vandetanib) has shown promising results and may soon become available. This agent is a dual inhibitor and targets the epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR). It also appears to inhibit RET-tyrosine kinase activity, an important  driver of cell growth in MTC.

Results from a double blind phase III trial (ZETA study) presented at ASCO 2010, showed that treatment with Vandetanib significantly extended progression free survival with a 54% reduction in the rate of disease progression compared to placebo.

Vandetanib (Zactima) is very likely to be studied in other solid tumors given its ability to target multiple receptors. Stay Tuned.