PRRT and the promise it holds for cancer treatment

As we continue our conversation on Precision Medicine for cancer, a popular therapy used to treat NET tumours or Neuro Endocrine Tumours is PRRT or Peptide Receptor Radionuclide therapy.
Neuroendocrine tumours are a rare form of cancer and originate from Neuro endocrine cells in the body and hence the name.They are different from adenocarcinoma’s and often do not do not respond well to chemotherapy, the 1st line of treatment for most cancers.

By administering radioactive protein lutetium octreotate, it is possible to treat NET tumours or neuro endocrine carcinoma with precision and offset progression of disease.

PRRT for neuroendocrine tumour
PRRT treatment for metastatic cancer cells spreading and growing. Tailor-made precision medicine based on genetic profile and molecular structure of the tumour.

In PRRT a peptide or a cell targeting protein is combined with a small amount of radio active nuclide creating what is called as a radio peptide. The radio peptide when injected into the patients blood stream travels and binds to a neuro endocrine tumour, delivering a high dose of radiation to the tumours. This also limits damage to the nearby healthy tissue and hence lesser and milder side effects than chemotherapy.

What kind of cancers can be treated by PRRT?

Along with Neuroendocrine tumours, carcinoids, islet cell carcinoma of the pancreas, small cell carcinoma of the lung a form of lung cancer, pheochromocytoma (a rare tumor that forms in the adrenal glands), gastro-enteropancreatic (stomach cancer , intestine cancer and pancreas) neuroendocrine tumors, and rare thyroid cancers that are unresponsive to treatment with radio iodine are often treated with PRRT.

Role of PRRT is also being explored for treatment of prostate cancer.

When is a patient a candidate for PRRT ?

Patients with following conditions are often proposed for PRRT

  • When neuro endocrine tumours are not responsive to other lines of cancer treatment
  • When surgical removal of tumours is not possible at current stage, PRRT may be used to reduce size of the tumours.
  • PRRT is also a treatment option for last stage inoperable cancers when metastasis has set in.
    The main aim of PRRT is then to slow down progression of disease, offer relief and prolong life.

However, not all neuroendocrine tumours respond to PRRT. First an OctreoScan is done. If the patient is found to have a positive OctreoScan and meets other requirements, PRRT is proposed.

What happens during PRRT ?

For patients having a positive octreoscan, to start with an amino acid solution is delivered to protect the kidneys.

As most net tumours have a lot of a specific type of surface receptor, a protein called somatostatin. Octreotide, is a lab version of somastostatin. During PRRT, a dose of radio nuclides such as Lutetium, Yttrium are often combined with octreotide and injected into the blood stream.

Molecular imaging and scans follow to see whether the radio peptide has latched on of the tumour sites correctly.

The entire session usually lasts for about 4 hrs and is often done as an out patient procedure.

The main goals of PRRT hence are to provide symptom relief, to stop or slow tumor progression and to improve overall survival.

Advantages of PRRT ?

PRRT along with other molecular therapies or targeted therapies offer excellent results as they are tailor made keeping in mind molecular properties of the tumour and also biologic characteristics of the patient.

PRRT is offered in Germany , USA, UK and other developed countries at a significant cost, In India, a single session of PRRT costs approx USD 6300.

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Understanding Precision Medicine for Cancer.

We often hear of Precision Medicine for Cancer, but what is Precision Medicine, how is it different from standard treatment protocols and what can be the benefits for choosing Precision Medication over standard protocols?

The diagnosis and treatment of cancer at a cellular or molecular level is known as Precision Medicine.

Cancer
Precision medicine : Tailored medication for cancer based on specific patients, genetic profile .

Cancer is a heterogenous disease, with different genetic profile not only between patients with different cancers but also differences in genetic , molecular and cellular profile even within the same type of cancer.

All cancers are genetic by nature and with cellular profile changing over time even in the same patient, till now no single drug is known to cure even a single type of cancer let alone different types of cancer’s.

Standard chemotherapy protocols focus of administering standard chemotherapy drugs ( one size fits all) without taking into account cellular or genetic profile of the patient.

Precision medicine on the other hand focuses on accurate and effective treatment to each patient based on the genetic profile, the proteins feeding the tumours or the cancers.

There are sufficient number of detractors even amongst the best doctors but precision medicine or administering drugs based not a specific tailored patient profile not being the best option is a pre mature conclusion.

This week being Breast Cancer week, let’s shed some light on Precision medicine for breast cancer.

Breast cancer treatment in India beyond surgical options of lumpectomy, mastectomy involves administering chemotherapy and radiotherapy, with chemotherapy being the first line of treatment.

Difference in outcomes depends upon whether the patient has been tested for HER2(human epidermal growth factor receptor 2), ER, PR or not.

For patients testing positive for HER 2, addition of trastuzumab to chemotherapy slows down disease progression. Lapatinib plus chemotherapy (i.e., capecitabine) achieved a longer median time to disease progression compared with chemotherapy alone.

A combination of pertuzumab, trastuzumab, and chemotherapy further improved the median overall survival time to a median of almost 5 years compared with a combination of only trastuzumab and chemotherapy for a median of 3 and half years.

Similarly treatment with ado-trastuzumab emtansine, a conjugate of a HER2 monoclonal antibody and a cytotoxic drug, significantly improved the length of progression-free survival and overall survival with lower adverse effects when compared with lapatinib and chemotherapy

The above examples clearly show how genetic profiling, identification of key mutations like the Bcr-Ablfusion or HER2 can benefit a large number of breast cancer patients.

Genetic profiling also enables identification of molecular targets for intervention.Cell death is caused by a combination of deficiencies in the expression of two or more genes, whereas deficiency in only one of these genes can increase viability or enhance multiplication of mutant cells. For example, BRCA (mutant gene responsible for particularly aggressive breast cancers( and poly ADP ribose polymerase (PARP) genes were found to have a synthetic lethal relationship.

For example, by using olaparib, a PARP inhibitor, to treat BRCA-mutant ovarian cancer patients, the progression-free survival of BRCA-mutant ovarian cancer patients was significantly prolonged by olaparib compared with standard chemotherapy protocols.

This methodology focusses on identifying cancer vulnerabilities and subsequent tailored treatment based on patient profile.

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