The Up Side Of Targeted Drugs Isn't All About Efficacy

When my sister Paula was treated for Acute Myeloid Leukemia a few years ago, her doctors did not have any of the latest miracle cures available (such as Gleevec, a drug that has literally revolutionized the treatment of Chronic Myelogenous Leukemia since its 2001 approval). Instead, they had to rely on the broad-spectrum chemotherapy drugs daunorubicin and cytarabine -- old stalwarts on our war on cancer that date to the 1960s.

Chemotherapy agents work by poisoning all the quickly dividing cells in the patients body, whether they're cancerous or healthy. When they're effective, they kill all or nearly all the cancerous cells before they kill the patient. But they inevitably come with a raft of very serious and often (temporarily) disabling side effects. Like many patients undergoing chemotherapy, Paula felt for months on end as though the treatment may have been worse than succumbing to the disease.

That's why the move by medical science into more targeted cancer therapies -- ones that either deliver a therapeutic dose to a specific or localized site in the body or consist of molecules specially designed to bind only with certain cell types -- has been hailed so broadly. Benefits include fewer or smaller doses given to the patient, greater confidence that the drug will find and destroy cancerous cells, and, perhaps most importantly to the patients, fewer and less severe side effects. And as the fields of genomics, proteomics, and metabolomics advance at a lightening pace, we are quickly learning much more about what makes cancers unique and how to target them effectively.

Unfortunately, the very high hopes we have for targeted drug therapies in these early days in their development are all too frequently accompanied by disappointment (see here and here) as one targeted therapy after another has proven to be ineffective or far less potent than we once imagined they would be. Experience is mixed, to be sure, and a handful of targeted therapies, such as Gleevec, have proven to be real breakthroughs. As the New York Times detailed two years ago in a three-part series of articles, the now-approved drug Zelboraf (then being tested in clinical trials under the moniker PLX4032) "produced seemingly miraculous results in some patients with [metastatic] melanoma" and a very specific genetic mutation.

However, in spite of the mixed clinical trial results related to efficacy, a new study published in August edition of the journal Annals of Oncology has found that targeted drugs appear to be living up to the hype with regard to safety. On average, patients in phase I clinical trials of targeted cancer therapies experience a markedly lower rate of the most severe (grade 3 and 4) adverse events associated with drug toxicity and fewer and less severe physical side effects than do patients undergoing traditional chemotherapy.

The study analysed data from 687 patients in 36 Phase I trials on a variety of different cancer types. And the findings offer some genuine hope to patients. "The theory behind targeted drugs is that they should affect only cancer cells that have a specific fault and spare healthy cells, which we hoped would lead to higher rates of efficacy and lower rates of side-effects," the study's lead author, Rhoda Molife of the Royal Marsden NHS Foundation Trust near London, told World Pharma News. "It's very pleasing that our study seems to back this up, at least in the context of Phase I trials."

Of course, the news isn't all good. World Pharma News also reports that, "for targeted drugs, the most common toxicities were gastrointestinal -- such as loss of appetite, diarrhoea and vomiting -- and fatigue, while side-effects for cytotoxic drugs are generally haematological or cardiovascular in nature." So, although targeted cancer therapies have fewer side effects, being treated with them is still no walk in the park. But the study's findings are one more bright spot in our slow but steady march to conquer the Emperor of all Maladies.

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