Lung Cancer / Mesothelioma
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Loading ...Because the anti-angiogenic drug avastin (bevacizumab) has been associated with some degree of increased risk of bleeding since the beginning of its development in lung cancer, the key trials have historically excluded patients who have been on blood thinners, at least at the standard dose (full dose anti-coagulation, or FDAC). In fact, though, patients with colon cancer have historically not been restricted, so the question has really been whether it’s necessary to restrict NSCLC patients who need FDAC from receiving avastin. In the US-based ECOG 4599 trial that compared chemo (carbo/taxol) alone to chemo/avastin and led to avastin’s approval (abstract here), patients who developed a blood clot that required blood thinners were taken off of the study. But is that necessary?
The bit of evidence we have about FDAC and avastin comes from the AVAiL trial done in Europe that compared chemo (in this case, cisplatin/gemcitabine) and placebo to the same chemo with either low dose or high/standard dose avastin. While patients on the AVAiL trial were not eligible if they were already on FDAC before the trial, the study did allow patients who developed a blood clot while on treatment to stay on the trial after initiating blood thinners. This gave an opportunity to compare the rates of bleeding complications among the patients not on FDAC to those who started FDAC and continued with avastin.
Developing blood clots is pretty common among patients with cancer, especially those with adenocarcinomas, who were the clear majority of patients on this trial that also excluded patients with squamous cancers. A total of 86 patients, divided pretty evenly among placebo arm, low dose, and higher dose avastin, were followed on while on FDAC along with their treamtent. They were compared to 900 other patients who remained off FDAC. As presented by Natasha Leighl from Toronto (reference here), there were no serious or fatal pulmonary hemorrhage events (coughing up blood) in patients on FDAC while also on avastin; there was a higher risk of bleeding in all patients on FDAC, including those who received placebo instead of avastin, but the real excess of bleeding events were just the mild grade 1 episodes like slight blood streaking with a cough, or a bloody nose.
Other studies are beginning to look at blood thinners with avastin and other antiangiogenic drugs, and at this point it’s really to early to declare it safe to give them together, but there also isn’t a clear signal of a significantly increased risk of bleeding, at least not beyond the risk of bleeding we see in patients on blood thinners overall. I’ll update with any new information if we see more study results presented at the ASCO meeting in early June.
Posted in: Anti-angiogenic agents, First-line treatment, Lung Cancer, Non-Small Cell Lung Cancer (NSCLC), Stage IV/Advanced/Metastatic NSCLC, Treatment
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I have adenocarcinoma and was not aware until recently, that blood clotting issues were one of the potential problems with this. I was not told about this, or signs and symptoms to report. Can you tell me how likely it is that I would develop this problem ( i.e. Percentage?)and in what form it most commonly takes (P.E.? DVT?) Fore warned is fore armed.
Thanks.
Terryl
Terry,
The rate of blood clots in lung cancer, on chemo alone would be in the 1-2% range, and it may increase to 3-4% on avastin. In these studies, the numerical increase in thromboembolic complications has not been statistically significant.
For a deep vein thrombosis in the leg, you’d generally note one leg to be swollen, red, and painful, most typically in the region of the calf. For a pulmonary embolus, or clot in the lung, sudden onset of chest pain not clearly related to exertion, high heart rate, and shortness of breath would be the leading symptoms.
-Dr. West
Dr West,
After all I had been reading and hearing I assumed the rate of coagulation problems would be much higher than that. Thanks for the info. I guess I will just push that to the bottom of the list of things to worry about. Tomorrow I go for my first scans since finishing chemo…I have enough “scanxiety”, I am glad I don’t need to worry about thrombosis as well. 
(Cancer has turned me into a hypochondriac). Knowing these stats also helps me feel more comfortable about the possibiliy of using avastin should it ever be presented to me in a treatment plan. Out of curiosity, do you think that if a patient is on anticoagulants, and avastin is the treatment of choice, that monitoring pt/ptt/inr and adjusting dosages of anticoagulant accordingly would be adequate to prevent an increase in complications from bleeding with the combination of blood thinners and avastin? Or is the bleeding caused by Avastin some how created by a mechanism different from the way warfarin works? Are the changes in bleeding time with Avastin as sudden and dramatic as they can be with too much anticoagulant therapy? or is it more insidious. I am a little confused ,,I was under the impression that avastin only caused bleeding problems, but according to your last post it also increases clotting problems in a small percentage of patients?Just curiosity here, thank goodness, for today, I really don’t have to worry about it.
Thanks again
Terry
Terryl
Terry,
The bleeding and clotting problems sometimes seen with avastin aren’t well understood, and bleeding isn’t only seen in patients with higher levels of blood thinning activity than intended. It basically is pretty idiosyncratic, so the time line is unpredictable, as is our assessment of who will have complications. You certainly can’t avoid issues completely by just monitoring the blood (INR) especially well.
-Dr. West
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