Avastin

A few decades ago, we visited Sol Rubinow (a theoretical physicsist, applied mathematician, biomathematician, fast chess champion, bridge expert, raconteur extraordinaire) shortly before his demise in the wake of an operation for a malignant brain tumor. He was fully cognizant of his situation and had all his mental faculties. He looked straight at me and said, "The only thing that can save me now is a miracle." I did not then and I do not now understand what he meant or why he said that. I suppose it was his way of giving up hope while retaining some hope, in what was according to medical opinion a hopeless situation.

I am not expecting a miracle (though I would not mind a good break at some point). But I am haunted by the feeling that I ought to try do something about Barbara's condition. Our oncologists have set us afloat in a sea of anguish with the advice that we simply make Barbara comfortable. That is, as I understand it, that we should settle down to a monotonic decay. Yet one hears that there are other courses to set. They may all reach the same destination but they may take us on different routes, some even worse than a steady decay, and none that may be called good. Would it be miraculous to happen to choose the least bad of the routes? As you can guess, I am wondering whether I should be getting some further treatment for Barbara, something that might help a bit without causing a lot of damage.

As I discussed this question with Steve C. one evening, we both were motivated by the striking improvement in Barbara's state without any treatment since the standard run of chemotherapy and radiation in October. She has been feeding herself with a bit of guidance and encouragement, she can walk to the dining room (with some help) and she is talking, engagingly if not entirely fluently. She is in there trying to get out. Should I be thinking of rocking the boat by trying to help her with that?

Of course, I have sought advice, some of which has already been reported in these bulletins. In this bulletin I'll lay out the case that has been made for and against Avastin, a drug that is often used as a follow up to the standard treatment. I would be glad to have your opinions about all this.

First, let me recall the report of the examining committee at MSKCC:

SPIEGEL, BARBARA
November 29, 2010
NEUROLOGY: BRAIN TUMOR CONFERENCE

This case was discussed at our multidisciplinary brain tumor conference in the presence of the attending physicians of the department of neurosurgery, radiation oncology, neuro-oncology and neuroradiology.

Barbara Spiegel is a 72 year old woman diagnosed in May of 2010 with a left frontal astrocytoma, [Ed's note: In fact the diagnosis from MSKCC in May was of a stroke. The diagnosis of a tumor was not made till late June.] which was low grade on biopsy [Ed's note: The biopsy was performed circa July 1 and indicated a grade III astrocytoma.] but behaved as high grade radiographically. She was treated with RT and Temodar that was completed on October 5th 2010 during an inpatient stay because of poor mobility. She did not have gross resection because of the tumor location. She now has global aphasia and poor gait despite VP shunt placement in September 2010. She was readmitted to the hospital from the nursing home because of lethargy that has improved after increase in steroids. Spine MRI shows a plaque of enhancement in the cervical spine.

The Tumor Board recommendation was palliative care since the patient's overall condition and neurological debilitation precludes her from returning to live at home.

Anna Delios, M.D., Neuro-Oncology Fellow AD
Internal cc: Antonio Omuro, M.D., Jerome B. Posner, M.D., Philip Gutin, M.D., Yoshiya Yamada, M.D.

I asked Dr. Roy Lackey, my primary care physician, for his advice in the matter. His reply:

Any intervention is worth considering. Avastin is a relatively benign therapy and is an interesting and potentially very successful treatment. I would go for it.

Dr. Jerome Posner, a respected authority, wrote this on Nov. 12:

The drug [Avastin] does seem to have salutary effects on gliomas, but the effect is short-lived and there is some evidence that the drug actually promotes spread of the tumor. Dr. Omuro's view is that some of the worsening of the MRI and worsening of her clinical symptoms may represent pseudo-progression [Predrag's note: Pseudoprogression looks and acts like a progressing tumor, but it is actually due to necrosis (death of cells) and other inflammation arising from radiation and chemo. Pseudoprogression would remain stable in size and could eventually go away.] rather than growth of the tumor. If so, it is possible that she may improve enough to return home and perhaps be a candidate for Avastin. However, although I am sorry to say, I am dubious that either spontaneous improvement or any major response to Avastin is likely.

Sigmund Hsu (a high school classmate of Louis Tao) has worked at MSKCC and is a very astute and sensible person. I asked him what to think about this diversity of opinions. He had this to say:

That is somewhat the nature of the beast. Even at MDACC with 10 neuro-oncologists, there was a continuum from conservative to aggressive. In the end as long as the proper conversations have occurred regarding risk, honest benefit, and whether the treatment is more for the patient or the family, the decision will be the correct one. If avastin was not safe enough or efficacious enough, it would not have been moved into front line trails in combination with temozolomide and radiation therapy as in the RTOG study. If I were to try anything - avastin would be the first thing to goto. They are a littte far from you, but one our our fellows, named Jai Grewal www.nspc.com/physicians.html, has been out in practice in North Shore, LI for some time now. He is a very solid physician and would give a nice second opinion having trained away from the NorthEast.

The net effect of these letters was that I was in favor of trying Avastin. But Barbara's sister was strongly opposed and I felt that I should heed her feelings especially given that she worked for years supervising drug trials. Here is Mimi:

I have been hoping and praying, even without the FDA's decision, that because of the side effects of Avastin that you would not let her get this toxic drug.

The FDA's decision mentioned is the recent action to no longer permit Avastin to be given to treat breast cancer. That decision is likely to be appealed. On the other hand, here is Karl Lauby, a friend, in a letter to his friend about the experience of his wife with Avastin:

I guess all the fuss in the popular press about Avastin and some chemo combination, (a cocktail, right?) is about the variation that Lila received that led to this dramatic drop in her CA 125 I recorded in June 2008. According to my notes, that went on six months to January 2009. Then we tried weekly taxal. Then we tried the trial at MSKCC which did not work and things went downhill. So it appears to me Lila got a little more than the reported average of four months from this Avastin combination. (I assume cytoxan is form of close to standard chemo theapy.) I just wish we had not started to slide in the summer of 2009. I guess the nature of Stage IV ovarian is that the slide starts sometime. Just wish we could have kept on the level longer.

Here we are speaking of a case of ovarian cancer, so the relevance of the experience may be in question. But my impression is that the statistics of this kind of thing that one reads about have to do with averages. Yet there are fluctuations such as the one Karl reports. But one does not even know if the fluctuations are due to the treatment. And the gains in any case are not great. For the moment I have not proceeded with Avastin because the risks that have been mentioned by some correspondents seem to have outweighed the chances of gain. Perhaps the next step is to contact Dr. Grewal as Sigmund Hsu has suggested.

see also:
Avastin Decision Not Based On Cost: FDA Official
FDA Will Pull Breast Cancer Indication For Avastin
Roche Suffers Another Setback Over Avastin
Roche Sends ‘Dear Doctor’ Letter, But Not In The US
Cancer Patients Petition The FDA Over Avastin
BCA’s Brenner: Avastin And FDA Approval Standards
November 9 2010 post on Avastin