Although in the last few years there has been a greater focus on low molecular weight heparins (LMWHs), which are injected, the oral anticoagulant (blood thinner) has been studied in this capacity and is certainly widely used in clinical practice for patients with blood clots due to its oral administration, which is desirable particularly if treatment may be indefinite.  This agent interferes with several proteins involved with the body’s normal mechanism for blood clotting, which is good if you need to heal a wound, but it’s a delicate balance that is harmful if people develop clots more often than they’re needed, which is often the case with cancer.  We know that cancer patients who develop a blood clot are at a higher risk of a recurrent blood clot than other people who don’t have cancer but have a blood clot. 

   Although heparin has been more extensively studied in this setting, there is some limited evidence that coumadin may have some direct inhibitory effects on tumor growth and metastatic spread (abstract here).  Typically, the results in actual people are more complicated.  In 1984, a large trial with 431 patients from the VA system with a wide range of cancer types (lung, head and neck, colon, and prostate cancer) were randomized to receive chemotherapy with either life-long coumadin or a placebo (abstract here).  There were no significant differences in overall survival for the general cancer population, but among the 50 patients with SCLC, median survival was doubled (50 vs. 24 weeks, p = 0.03).  Here are the survival curves for coumadin vs. placebo with NSCLC and SCLC:

 (click to enlarge)

There is actually some evidence in test tube models that SCLC cells continue to have clot-promoting activity that isn’t present with other cancers (abstract here), and that therefore SCLC may be uniquely affected by coumadin.  However, subsequent studies have not demonstrated as consistent of a benefit.  A trial performed by CALGB with 294 patients with ED-SCLC gave chemo alone or with coumadin (abstract here).  Encouragingly, the response rate was higher when coumadin was added (38% vs. 10%, p = 0.12; disappointing numbers overall, but this was before platinum/etoposide, our current standard); the survival was not significantly better for the recipients of coumadin with chemotherapy (37.0 weeks) compared with chemo alone (31.6 weeks).  Another trial in SCLC by the CALGB (abstract here) enrolled 347 patients with limited stage to receive chemo and radiation either alone or with coumadin during treatment.  As in the CALGB trial in ED-SCLC, there was a non-significant trend toward a superior median survival  when coumadin was added (21.4 months vs. 18.6 months).  Perhaps significantly, the target range of blood thinning in the latter study was lower than what would be considered “therapeutic” for treating blood clots.  There was also a pooled analysis of several trials (reference here) that showed only a non-significant trend of improved survival at one-year for cancer in general and also specifically in SCLC.

   One final, more recent study deserves mention.  Lee and colleagues did a study of 602 patients with cancer (about 15% with lung cancer, not divided into SCLC and NSCLC) who developed a blood clot, randomizing them to 6 months of treatment with either oral anticoagulatio (almost always coumadin) or a daily injection of Fragmin/dalteparin (abstract here).  While there was no overall difference in survival between the two groups, when the investigators broke down the groups into the those with or without metastatic disease at the time of treatment, and they found that the patients without metastases, and presumably with a better overall prognosis, had an approximate 50% improvement in survival at one year after starting the trial if they received Fragmin instead of oral anticoagulation:

For now, the evidence on coumadin in lung cancer has demonstrated some promising leads, but at the end of the day, there is not enough evidence to declare a benefit for coumadin in lung cancer, even SCLC, especially when you factor in that blood thinners increase risk of bleeding complications.  We’ll explore additional data about low molecular weight heparins next (like most of cancer management, it’s not a slam dunk easy answer).