When I was young enough still to consider myself rational, I was irritated by patients who tried any remedy in desperation to save themselves from their fatal disease. I have long since mellowed and when an acquaintance of mine with glioblastoma, a rapidly fatal brain tumor, decided recently to go to India to try Ayurvedic medicine, all I could do was wish him luck – sincerely so. After all, the scientific medicine — which he would continue to take while there — offered him little enough hope, a few months at most. (This case, incidentally, illustrates an important point: alternative medicine, so called, is not generally alternative, it is additional.)
Two trials of a very expensive monoclonal antibody, bevacizumab, in glioblastoma, published recently in the New England Journal of Medicine, make disappointing or even dismal reading. This antibody is directed at vascular endothelial growth factor that promotes the growth of new blood vessels; glioblastoma is a tumor particularly rich in new blood vessels, and so it was hoped that by preventing them from forming, tumor growth would either be prevented or at least slowed. Early results were promising but as has so often been the way in the history of medicine, early promise is not fulfillment of promise.
In one trial, for example, 637 patients with this terrible tumor were randomized to conventional treatment plus placebo and conventional treatment plus bevacizumab. Although the latter had a slightly longer period free of progression of the tumor, their overall length of survival was not increased, and indeed they suffered so many more side effects that the overall quality of their lives was worse. The patients taking bevacizumab survived on average 15.7 months; those taking placebo survived 16.1 months. The authors of the paper end:
In conclusion, we did not observe an overall survival advantage first-line use of bevacizumab in patients with newly diagnosed glioblastoma. Furthermore, higher rates of neurocognitive decline, increased symptom severity, and decline in health-related quality of life were found over time among patients who were treated with bevacizumab.
This makes rather odd the concluding words of an editorial that accompanies the trials in the Journal:
Finally, it is worth noting that despite its limitations, bevacizumab remains the single most important therapeutic agent for glioblastoma since temozolemide. Ongoing and future trials will better define how and when it should be used in this population of patients for whom so few treatment options currently exist.
Clearly the viewpoint of the oncological researcher is not that of the sufferer of the disease: he is looking far into the future, while the poor patient (all the poorer if he has to pay for his drugs) is thinking rather less far ahead.
Another paper in the same issue of the Journal reports something slightly more favorable to the drug, this time in cases of advanced and metastatic cancer of the uterine cervix. Here a trial showed that those treated with bevacizumab survived four months longer on average than those who were not so treated, and survived four months longer (that is to say, 17 rather than 13 months).
This raises the unpleasant question of whether treatment that costs so much to administer is good value. Value for whom? For the ill person herself, for her family, for society as a whole? Eventually, of course, the treatment, like flat-screened televisions, will become much cheaper; but in the meantime the question will be asked. The answer might depend on who is paying.
How much would I pay to survive an extra four months of life with an illness I knew to be fatal? I don’t think this is a question that I can answer in the absence of it being a real choice. It depends on too many variables.