[gdpawel]

The FDA had been thinking about mixing cocktails of drugs still in development. Exactly what drugs they have in mind is still up for debate. However, it has been suggested by some that perhaps Genentech/Roche should use assays like the Microvascular Viability Assay (MVA) with functional profiling to identify a potential target population of breast cancer patients that it thinks will benefit from the drug Avastin and then conduct a randomized clinical trial among this group. It's not a case of just throwing Taxol + Carboplatin in with Avastin and expect it to work for all cancer patients in all types of cancers.

Of course, this kind of strategy has been going on for years with cell culture assays, and the latest example is the Avastin controversy. Avastin combined with Carboplatin and Taxol has improved the survival of lung cancer patients. Avastin plus Carboplatin and Taxol improves the survival of some breast cancer patients. The problem is that it doesn't improve the survival of all breast cancer patients.

When the FDA rules on the clinical utility of a drug, they use a broad-brush approach that looks at the global outcomes of all patients, determining whether these glacial trends reflect a true climate change. The problem is that while Bethesda, Maryland may not be noticing significant changes in ocean levels, people who live on the Maldives are having a very different experience. As these scientists ponder the significance of Avastin, some breast cancer patients are missing out on a treatment that could quite possibly save their lives.

One breast cancer patient's life saving therapy is another's pulmonary embolism without clinical benefit. Until such time as cancer patients are selected for therapies predicated upon their own unique biology, we will confront one Avastin after another. The solution to this problem has been to investigate the VEGF targeting agents in each individual patient's tissue culture, alone and in combination with other drugs, to gauge the likelihood that vascular targeting will favorably influence each patient's outcome.

The problem with Avastin is the same thing that was a problem with AZT for HIV/AIDS. Early results, then rapid resistance. Solution is combination therapy to attack different targets. Tumor vasculature needs VEGF to survive. Avastin removes VEGF, killing blood vessels. But other proangiogenic factors can substitute: FGF, PDGF, ephrin A1, angioprotein 1, IL-8 etc.

We need to attack these other targets, as well. But "how" do you attack these other targets? If you can achieve this, then you may not need the other drugs, which really don't get into the tumor so well. But angiogenic attack provides true selective toxicity, something which is sorely lacking with all of our other treatments.

There are numerous drugs that can prolong life in breast cancer patients and slow the spread of cancer while improving quality of life, at so much less cost. In cancer medicine, it's not a case of throwing targeted drugs like Avastin at the problem. It's knowing "what" targeted drugs and "how" to use them in "individual" patients (not average populations). It is not clear that the purported mechanism is really what's happening.

The problem is that few drugs work the way oncologists think they do and it takes far more "information" to think through what it is they are using them for. I don't need to know how my laptop or television works, as long as it works and I feel the same way about anti-cancer therapies. Theory doesn't matter as much as the evidence that it does what we want it to do.