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A combination of Oxaliplatin, Irinotecan, Fluorouracil and Leucovorin (FOLFIRINOX) chemotherapy given to individuals with metastatic pancreatic cancer resulted in superior Response Rates, Progression Free Survival and Overall Survival compared to single agent Gemcitabine. For the first time, we now have a regimen that has demonstrated survival benefit for this hard-to-treat cancer.
This data was presented at the 2010 ASCO meeting
GVAX is a therapeutic cancer vaccine, developed to induce antitumor immunity. Traditional vaccination against specific bacterial and viral infections involves the injection of the specific weakened bacteria/virus or a structural component of the bacteria or virus. The body then mounts an immune response and is ready to respond to an infection associated with that specific bacteria or virus.
Based on the same principle GVAX, a cancer vaccine, comprises of patient derived tumor cells, that are irradiated to prevent it from dividing and is then genetically modified to secrete GM-CSF (Granulocyte Macrophage Colony Stimulating Factor). GM-CSF is important for the growth and activation of dendritic cells also known as Antigen Presenting Cells. This vaccine when injected activates the dendritic cells, which in turn stimulates the patients immune system to attack the vaccine tumor cells, which are in fact similar to the patients original tumor cells. This vaccine therefore theoretically boosts the body’s immune system to fight the patients tumor, without causing collateral damage.
The FDA granted Orphan Drug Status for GVAX vaccine to treat pancreatic cancer. An orphan drug is an agent developed to treat a rare medical disorder affecting fewer than 200,000 people in the United States.
GVAX vaccine is being studied in other types of cancer as well. It should however be noted that vaccines by themselves may be of benefit only for patients with low volume disease with adequately functioning immune system.
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.
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.
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
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.
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.
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.
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.
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.