Avastin

[raneyf]

Does anyone know if Avastin is like a typical cancer drug, where the cancer eventually mutates and it becomes ineffective? I'm sure the answer is probably yes - but I was thinking maybe the cancer eventually progresses because some blood vessels are able to form or whatever, then chemo again to knock it down and keep on the Avastin also because it slows it down? Anyone know? I have a couple of weeks before I see my doctor again and was curious.

Thanks,

Raney

[RandyW]

Bevacizumab (Avastin®). Be vacizumab is a monoclonal antibody directed against VEGF. A monoclonal antibody is a genetically engineered, humanized antibody which targets and attacks a specific antigen. In cancer, monoclonal antibodies are designed to target specific cancer cell antigens. The antibody initiates an immunologic response which eliminates cells associated with the antigen. Bevacizumab is a monoclonal antibody designed to attack cells that over-express the VEGF protein as an antigen. By inhibiting vascular endothelial growth factor, the drug acts as an anti-angiogenesis agent.

Currently, bevacizumab is in clinical trials in renal cell carcinoma, nonsmall cell lung cancer, and metastatic breast cancer. Thera peutic dosages are still under investigation. Recently, it was approved for first-line treatment of metastatic colorectal cancer. Used in combination with intravenous 5-fluorouracil (FU)-based chemotherapy, bevacizumab has shown increased survival in patients with metastatic colorectal cancer. The recommended dose is 5 mg/kg given once every 14 days as an intravenous infusion. This drug should not be administered as an IV push or bolus dose. Infusions should not be mixed with dextrose solutions. The half-life of this drug is approximately 20 days. The most serious adverse effects associated with bevacizumab are gastrointestinal perforation, wound healing complications, hemorrhage, hypertensive crises, nephrotic syndrome, and congestive heart failure. Serious episodes of hemoptysis have been reported in patients with lung cancer. No studies have been conducted in patients with renal or hepatic impairment. Bevacizumab therapy should not be initiated for at least 28 days following major surgery because of the potential for impaired wound healing. Infusion reactions have been rare (Genentech, n.d.; National Cancer Institute, n.d.).

Does this help With your questions? Best I think I could find

[DrWest]

Raney,

The short answer is that Avastin isn't chemo, but a targeted therapy that can potentially be useful on its own or modify the effects of chemo it's given with.

The bigger question is whether, if a cancer grows on a combination of chemo and avastin, has it become resistant to chemo, resistant to avastin, or both? We have seen over decades of treating lung cancer that it becomes resistant to the same chemo agents after a while, typically after 4-6 cycles at most (this is the case for the majority of cancers). So most of us would say that someone on chemo + avastin who then progresses would be well served by coming off of their current therapy and switching to a new treatment like second-line chemo (say, alimta, or taxotere) or tarceva (all 3 of these are FDA-approved and have shown evidence of benefits for 2nd line treatment). The key question is whether there would be a value in continuing the avastin and just switching out the drug(s) it's given with. That's generally what people do for herceptin in breast cancer -- keep the herceptin going with multiple different chemo agents it's paired with. But I would say that most experts don't favor continuing avastin after a patient progressed on it. There's also the small but real risk of a serious or even fatal side effect with it, which is for many people a risk worth taking if they haven't had avastin before and can hope and maybe expect to get a significant survival benefit. But in a setting where the benefits are expected to be lower, and maybe none, that risk may just tip the scale to it being a much less favorable choice.

There are several other targeted therapies being studied, including several that also block angiogenesis (tumor blood supply) by a slightly different mechanism, so I'd generally favor using different drugs rather than continuing an agent on which someone has shown progression.

And Katie, thanks for pointing in my direction. I hope people will come and see if I've got an answer to their question on my site. For the time it takes to put the materials together, it's worth it if people use them.

-Dr. West

[RandyW]

Thanks Again for volunteering your time.

[DrWest]

Raney,

I just read your LC bio and see that you are a never-smoker. That's among my strongest research interests, although the field has only just start to recognize that there's something distinct about never-smokers with NSCLC. Among those distinctions is the high likelihood of a very striking clinical benefit, in terms of response and survival, with EGFR inhibitors. I've described some of the particular issues about never-smokers in a couple of posts, listed here:

http://onctalk.com/2006/11/21/do-never- ... t-disease/

http://onctalk.com/2006/11/22/never-smo ... treatment/

I don't want to sound like an advertisement for Tarceva, because it's not shown to be clearly better than alimta or taxotere overall in a general population. But for never-smokers with LC, tarceva is often a very helful choice.

-Dr. West

[raneyf]

Thanks Dr. West. Unfortunately I tried Tarceva as first line therapy and progressed after 6 weeks. It doesn't look like I'm one of the lucky ones that it benefits. I appreciate your answer and your website - I visit it often and just haven't had a chance to ask my question over there. I'm doing well on my current chemo with the Avastin, going to Avastin alone after 3 more treatments. Hoping it will buy me some time. Thank you again.

Raney