The Death Of Chemotherapy As We Know It?

If you were diagnosed with testicular cancer in the 1970s, there would be a more than 30% chance it would kill you. Today it’s only 4%, as 96% of those diagnosed undergo complete remission, the word for “cured” in oncology-speak. The primary reason for this vast improvement in survival chances is chemotherapy. There is no questioning the treatment’s effectiveness. When used in conjunction with radiotherapy and physical surgery it can improve the chances of survival for most cancer types. The tide is changing however; doctors are starting to predict the end for chemotherapy as we know it, and here’s why.

Chemotherapy, however effective, can be extremely and permanently harmful to a patient, even after treatment ends. It works by introducing toxic chemicals into a patient’s body, designed to attack cells that reproduce rapidly, like cancer cells. Fortunately, in an adult body the reproduction rate of most cells is relatively stable, but most is not all, and things like hair cells, nail cells and the lining of the digestive system also attract the attention of the toxic drugs. For a long time this all-in approach has been the best way to attack cancer cells, but a string of recent clinical trials are approaching completion that deliver treatment in a much improved and overall safer manner. While the treatments in question differ somewhat they all share a common denominator -- accurate targeting.

Targeting cancer cells means no more collateral damage and a much higher quality of life for those undergoing treatment; if proven effective it could revolutionize cancer treatment.

Xalkori, Pfizer’s fastest growing drug by sales
Let’s begin with one treatment that is already approved and selling on the market.

One form of targeted cancer treatment that is already making waves, and is set to expand rapidly, is based in genetics and is commonly referred to as targeted therapy. Targeted therapy was born out of the human genome project, a global effort to map the entire human genome. As part of the project, scientists discovered 150 genes, which they now refer to as oncogenes. When mutated, all 150 of these genes demonstrate cancer-causing traits, for example, inhibiting the process that would normally put a stop to cell division. Targeted therapy involves patients taking drugs that specifically inhibit these oncogene mutations.

One well-known example is Pfizer’s (PFE) Crizotinib, branded Xalkori. Crizotinib received FDA approval to treat a form of lung cancer called non-small cell lung carcinoma in August of 2011, with the results showing that the drug shrank or stabilized tumors in 90% of 82 participating patients. It is also currently being trialed for use in the treatment of large cell lymphoma and Neuroblastoma, the most common cancer in children.

The Xalkori is Pfizer’s fastest growing drug by quarterly sales with a 191% sales growth rate since Q2 of last year. This kind of growth indicates in a Big Pharma company indicates a major shift could be on in oncology treatments, especially if these growth numbers continue. This is why I believe that several of these drugs coming to market could lead to a dramatic reduction in the use of chemotherapy.

Xalkori is one of the latest in a series of targeted cancer drugs that have put a serious dent in the use of chemotherapy in general. The most consequential to date has been imatinib, Novartis’ (NVS) Gleevec, which has all but eliminated chronic myelogenous leukemia with a 98% complete response rate after 60 months of treatment. No more chemotherapy there. Gleevec is Novartis’ number one blockbuster. Targeted cancer therapy is huge.

What other targeted therapies are in the pipeline?
With Gleevec being the first big breakthrough and Xalkori growing fast, what other targeted cancer therapies are in the pipeline?

One intriguing one relies on a process called electroporation. All eukaryotic cells (of which cancer is one) have an outer membrane called a phospholipid bilayer. This layer is essentially two layers of lipid molecules that wrap themselves around the cell, and hold the cells “innards” in. A relatively high voltage shock causes this membrane to temporarily lose its structure, and then reassemble itself.

OncoSec (ONCS), a company that specializes in electroporation for skin cancer treatment, is using this temporary loss of structure as a window of opportunity to deliver one of two things into the cells.

The first is a cytokine called IL-12. IL-12 is protein that, when inserted into a cell, triggers an immune response that causes T-Cells (one of the immune system’s fighter cells) to attack the cancer cells. The company’s ImmunoPulse program, its IL-12 delivery program, is in phase 2 of its clinical trials, with positive phase 1 results reported. The results showed 90% of treated metastatic melanoma lesions demonstrated local control, which simply put means that they stopped growing. 53% showed objective response, which means injected tumors actually shrank. 16% showed complete regression, which means that, for all intents and purposes, all their cancer disappeared. The timeline for the melanoma trials is as follows. Enrollment for the phase 2 trial was completed on June 18, long term progression free survival data on phase 1 is due any day now, and an end of phase 2 meeting with the FDA is tentatively scheduled for November. All in all, OncoSec is approaching a critical period with Immunopulse.

The second treatment OncoSec is working on is called NeoPulse and involves an anti-cancer drug called Bleomycin. Bleomycin is used in traditional chemotherapy to attack head and neck cancer cells, but it is extremely toxic and can cause severe side effects at the dose currently required including. To give you an idea, one of the worst is mucusitis, which destroys mucus producing cells (they divide quickly and are therefore attacked by the Bleomycin) and leaves a patient literally unable to swallow anything without crippling pain. Electroporating Bleomycin directly into a tumor, however, allows effective results at 1/20th of the current required Bleomycin dose, sparing patients these horrible side effects. ONCS’s NeoPulse program, which delivers the drug, again showed positive results in clinical trials. In the US, a phase 3 trial demonstrated a 90% success rate in killing locally recurrent or secondary tumors. In Europe, a phase 4 trial demonstrated similar success, with a 94% success rate in in killing local primary tumors without any recurrence. The timeline on Neopulse is more blurry, as the company’s primary resources are being invested in Immunopulse at present.

Another slightly less well-known targeted therapy drug is selumetinib. Selumetinib, currently undergoing development by AstraZeneca (AZN), is a drug that inhibits certain mutations of the BRAF gene, a gene associated with cell growth. Recently reported phase two trial data suggests potential efficacy in treating BRAF-mutated melanomas, with three out of five patients demonstrating tumor regression.

AstraZeneca is involved in 24 trials selumetinib in several different cancers including lung, colorectal, thyroid, melanoma, and pancreatic. Phase 3 is planned to begin later this year for non small cell lung cancer.

Yet another, Ganetespib, is undergoing a study conducted by its development company, Synta Pharmaceuticals Corp. (SNTA). Ganetespib inhibits a protein called Hsp90, which is reported to play a key role in the survival and reproduction of cancer cells. The study has already demonstrated some positive results, with 4 of 15 patients experiencing significant shrinkage of breast cancer tumors that are otherwise nearly impossible to treat.

What Does This Mean For Cancer Patients?
Treatment using the IL-12 cytokine described earlier, and other targeted therapy drugs, is in a technical sense chemotherapy because all attack cells that reproduce quickly. The major difference between the traditional chemotherapy approach, and the approach likely to take hold in the near future, is the side effects associated with the treatment. The quality of life that cancer patients experience is seriously reduced by the current standard of care treatment (chemotherapy, radiation and surgery), and while there will still be side effects associated with modern targeted treatments they will most likely be much less detrimental.

Will The New Therapies Become Standard Of Care Soon?
The current FDA approval system makes it very difficult for new drugs and treatments to become commercially available and targeted therapy, by its very nature, requires many different forms of drugs to treat the many different forms of cancer. Each of these drugs takes years to develop, and then an average of 12 years before they receive FDA approval. For this reason, it is unlikely that the standard of care treatment for cancer as a whole will change in the next year or two unless one of these in the pipeline is the next Gleevec for multiple cancers, something that is far-fetched; more likely it will be a step-by-step process for each caner. As each new drug is developed, it could become the standard of care treatment for the particular cancer it is used to treat. Having said this, many of the drugs in development will treat a number of cancers, and one that already has approval for treatment of one cancer is likely to be approved more quickly for treatment of another. This should cause a snowball effect in the uptake of the modern cancer therapies as they become more widely adopted.

Conclusion
All said, while an all-out cure for cancer might still be a long way off, the R+D undertaken over the last 30 years is finally paying off in the form of therapies that will make cancer treatable, and in turn bearable, for those living with it. Traditional chemotherapy and the side effects so commonly associated with it, will, in the not too distant future, hopefully become a thing of the past.