Author: RR

New Biomarker to predict Cancer Recurrence or Metastasis

RR

A protein variant of carboxypeptidase E has now been shown to induce tumor growth and metastases. By measuring the level of this protein in the tumor and surrounding tissue, we may soon be able to predict whether a tumor is likely to spread or has already spread. The predictability of tumor behavior, using this new novel biomarker, appears to trump the outcomes based on staging and grade of the tumor. The tempo of the disease even in patients with advanced cancer can be predicted measuring the levels of this biomarker, with tumors expressing high levels of this protein doing poorly. This  may also help the clinician determine when to treat a patient with cancer and when to just monitor without pursuing aggressive chemotherapeutic intervention.

These findings were published in the Journal of Clinical Investigation,  Feb  2011.

Environment and Cancer

RR

More than a third of Americans will develop some form of cancer during their life time. Interestingly 80-90% of the cancers in the western hemisphere has been attributed to environmental factors. With cancer being the second common cause of mortality in the USA, prevention of cancer related morbidity and mortality can be accomplished by avoiding environmental pollution with carcinogens and eliminating exposure to existing carcinogenic agents in the environment. This sentiment was eloquently verbalized by Dr. David Christiani in the March 3, 2011 issue of the NEJM.

Despite the progress made in cancer treatment and Genomics, we cannot lose sight of the fact that prevention is better than cure.

Breast Cancer – More is not necessarily better

RR

It used to be that patients with breast cancer requiring surgery had Radical Mastectomy until the 1970’s. It subsequently became clear that Modified Radical Mastectomy, a less aggressive surgical procedure was just as effective as Radical Mastectomy. The next major surgical advance in Breast Cancer was breast preservation with Lumpectomy, Axillary Lymph Node Dissection (ALND) and Radiation. This has been proven to be as good as Modified Radical Mastectomy. Because of the morbidity associated with complete ALND, the technique of Sentinel Lymph Node Dissection (SLND) was developed and it became clear that SLND by itself is as effective as ALND,  in early breast cancer, without the complications associated with ALND.

A randomized clinical trial results published in JAMA this month demonstrated that in women with invasive breast cancer and limited sentinel lymph node metastases, SLND was as effective as ALND. With this data, women diagnosed with breast cancer hopefully will not have to endure the morbidity associated with ALND which include swelling, pain, paresthesias and restriction of movement of the arm.

This philosophy of  ” more is not better” with regards to chemotherapy, held ground, after myeloablative therapy and transplantation for metastatic breast cancer patients showed no benefit. Hopefully newer “kinder and gentler” systemic agents will follow suit, just as the surgical techniques have evolved over the past 40 years.

Maintenance Rituximab

RR

The FDA on Jan 31, 2011 approved Rituximab as a maintenance treatment for patients with advanced follicular lymphoma, who responded to initial treatment with Rituximab plus chemotherapy. Follicular lymphomas are a subset of Non Hodgkins Lymphomas and are very responsive to chemotherapy or chemotherapy with Rituximab. They are usually incurable however, despite treatment with Rituximab plus chemotherapy. So think of this condition as a chronic disease. For this reason, prolonging remission duration is important, as the length of remission tends to be shorter with each recurrence.

In the PRIMA trial, which was a phase III study, maintenance Rituximab for 2 years given to those who responded to induction treatment with chemotherapy and Rituximab, delayed the risk of recurrence and improved progression free survival. These findings are relevant for patients who essentially have a chronic disease and are willing to pursue interventions that would delay recurrence of their lymphoma and therefore improve their quality of lives.

PARP Inhibition in Triple Negative Breast Cancer

RR

Patients with triple negative breast cancer have inherent defects in several DNA repair pathways. These cancer cells therefore become increasing dependent on another DNA damage repair pathway called base excision repair (BER) pathway, for survival. It so happens that PARP 1(PolyAdenosine diphosphate Ribose Polymerase) is an important enzyme regulating the BER pathway.  By inhibiting PARP1, the BER pathway is inhibited leading to extreme levels of DNA damage and eventual death of cancer cells.

In an article published in the Jan 20,2011 issue of the NEJM, the addition of a PARP inhibitor Iniparib to a combination of Carboplatin and Gemzar in patients with metastatic triple negative breast cancer, resulted in superior Response Rates, median Progression Free Survival and Overall Survival. This difficult -to -treat subtype of breast cancer may soon become extinct.

Improving Survival in Metastatic Pancreatic Cancer

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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 – Vaccine for Pancreatic Cancer

RR

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.

Everolimus for Neuroendocrine Tumors

RR

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

RR

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