FIGHTING THE CANCER WARS WITH A NEW DRUG CALLED VELCADE

And so we begin a new chapter in this saga called surviving with cancer. I’m subtitling this chapter or posting Velcade. What is that? Velcade is the trade name for a new product developed by Millennium Pharmaceuticals to fight a nasty blood cancer called multiple myeloma. Recently the uses of Velcade expanded when the U.S. Food and Drug Administration approved its use for fighting a version of NHL or non-Hodgkins lymphoma known as Mantle Cell B Lymphoma.

Readers of Mind Check may recall that Mantle Cell B Lymphoma is the disease that I was diagnosed as having back in late 2001 and for which I was treated first with a mixture of chemicals known by the acronym CHOP and later, that is, in October 2002, with a bone marrow transplant at Johns Hopkins Hospital. During both episodes I also received several infusions of a product called Rituxan.

Bad News, Right?

Readers of my previous posting to Mind Check will recall that I have just recently undergone a biopsy at Wake Forest University Baptist Hospital. That posting did not include the all-important pathology report of the two specimens removed from me laparoscopically because at the time I had not yet received it.

From the way I began today’s posting, you’ve concluded that the report was not what I was hoping to hear, that the pathologist saw evidence of the return of Mantle Cell B Lymphoma on the two slides that the surgeons made of what they took out of my abdominal area. Bad news, right? Yes, bad news, but I’m not ready to give up.

Problem with Procedure Repetition

As a relapsed victim of Mantle Cell B Lymphoma, I could repeat the procedures I went through in 2002—that is, the witches brew called CHOP followed by another bone marrow transplant and the extensive use of the agent called Rituxan, which is taken by infusion and which works by binding to a particular protein (the CD-20 antigen) on the surface of normal and malignant B-cells and thus triggering their elimination.

Back then, however, I was warned by an oncologist and expert on lymphoma that I should be prepared for the fact that each repetition of this blood cancer fighting combination could be expected to be less effective than the one before. How much better then to be taking a brand new agent, one that my body has not been exposed to before.

Learning Biochemistry of Cancer

Okay so that brings me back to Velcade and the reasons that I remain extremely hopeful despite a disappointing pathology report. Velcade did not exist as a viable option for fighting Mantle Cell B Lymphoma in 2002, but it’s available today. Trying to figure out how Velcade works has pushed me even deeper into trying to understand the causes of cancer and specifically blood cancer. It has pushed me to make my aging brain absorb complex biochemical concepts having to do with cell development including mistakes in cell development and cell death.

Velcade, generic name bortezomib, is a proteasome inhibitor. It is the first proteasome inhibitor to be approved for use in humans, but in reviewing some of the information on proteasome inhibitors on the Internet I see that it is not the only one and I am sure we will soon be hearing about the use of other such agents in the blood cancer battle.

Proteasome Inhibitor, What Is It?

What is a proteasome inhibitor? Sometimes when the body puts together groups of proteins to make cells it makes a mistake. What is supposed to happen is that these mistakes die, a process known as apoptosis, and are eliminated from the body. But what if they won ‘t die? What if they insist on growing? We call that process cancer.

“Proteasomes are responsible for the selective degradation of proteins when cells no longer need them,” says the Peptides International website. “Inhibiting proteasomes in cancer cells can disrupt protein regulation, which ultimately can lead to apoptosis or programmed death.” (http://www.pepnet.com/proteasome.html) This death is a good thing. We want errors in cell development to die and be eliminated, not to be perpetuated as cancer.

Helpful Publication

The best description of mantle cell lymphoma for the lay person that I have seen including causes, diagnosis and treatment options is published by the Leukemia & Lymphoma Society and is available by calling the society at 800-955-4572. (Ask for the document entitled “Mantle Cell Lymphoma” Number 4 in a series.) It is also available as a downloadable document in PDF format on the Internet. (http:// www.leukemia-lymphoma.org)

In reading this document one learns that the cancer causing error in Mantle Cell B Lymphoma has to do with a protein called cyclin D1. “MCL [Mantle Cell Lymphoma] is distinguished by over expression of cyclin D1 (a protein that stimulates cell growth) in almost all cases. The over expression of cyclin D1 is usually caused by a translocation between chromosomes 11 and 14.” Chromosomes carry the genes that convey our hereditary characteristics.

Transformation of a B Lymphocyte

Later the document tells us how this error gets turned into a full fledged disease. “Mantle cell lymphoma (MCL) is the result of a malignant transformation of a B lymphocyte in the outer edge of a lymph node follicle, called the mantle zone. The transformed B lymphocyte (lymphoma cell) grows in an uncontrolled way and the accumulated lymphoma cells form tumors in lymph nodes leading to their enlargement. The lymphoma cells can enter the lymphatic channels and the blood and spread to other lymph nodes or tissues such as the marrow, liver and gastrointestinal tract.”

Thus the war resumes for me using a new weapon called Velcade. What is at stake is something very dear to me, namely my life. I got through the first battles of this war in 2001 and 2002, and my hope is I will do at least as well in 2008. One of the things I have going for me is that I am still feeling strong and vigorous. I am no beaten warrior forcing his weakened carcass back into battle. No, I am beginning to see myself more like the biblical hero Samson once again doing battle with the Philistines.

I was reminded of the Samson image in a recent discussion of my medical situation with my friend Brooks Townes. After hearing of the latest twist in the saga of my battles with blood cancer, Brooks said, “I think of you as someone in a huge building that is about to collapse on him. Then the building does collapse. Huge pillars and huge ceiling pieces are falling all around you, but somehow nothing touches you, and you come out unscathed.” Let us hope that Brooks’s vision applies in this case as well.

To reach the author of Mind Check write Stephen.saft@gmail.com.

Copyright © 2007 by Stephen Alan Saft

BIOPSY FINALLY CARRIED OUT. LAPAROSCOPIC PROCEDURE WORKS.

Sometimes, especially when we are older, we are grateful for postponements of traumatic medical procedures. Yes, it would be better if they became permanently unnecessary, but then such miracles are extremely rare. And so I am grateful for the six month postponement of the medical procedure I previously wrote about in Mind Check, a postponement brought about by wife Harriet breaking her left or, in her case, “good” wrist.

My latest PET Scan, performed Oct. 19, showed that the small mass in my abdomen, previously the size of an olive, had grown to the size of a quarter and that it had gotten even brighter, indicating an increase in activity. Time to take action, right? That’s what my new oncologist felt, and she had previously recommended a conservative wait-and-see approach. How could I protest this time?

Target: Mass in Mesentery

Off to the surgeon, off to Carl Westcott, Assistant Professor of Laparoscopic and Bariatric Surgery at Wake Forest University Baptist Hospital in Winston-Salem, North Carolina. The target of Westcott and his team was located by the two CAT and two PET scans (the latter actually combinations of both PET and CAT procedures) in the mesentery, a web of tissue linking the organs of the abdomen, which also happened to be in the blood supply for the small intestine.

Was this mass evidence of the reoccurrence of lymphoma, cancer in the lymphatic system, for which I had been treated extensively in 2002? Was it evidence of cancer in one of the nearby organs such as the small intestine? If so, why had the two PET scans failed to show the possibility of cancer in these organs? Or was it a response to infection, infection generated by the chronic condition known as diverticulitis, a problem in the intestines which had first been spotted in me during a procedure known as endoscopy in early 2002?

Envisioned as Diagnostic Procedure

Whatever the findings, it was unlikely that the surgery would include the cure for my problem. No, the surgery was always envisioned as a diagnostic procedure, as what is called a biopsy. As such, it was always seen as a method of finding answers, not a cure in and of itself, and it was always envisioned as requiring the services of a pathologist and his or her microscope to complete the inquiry.

My fear going into the procedure was that the minimally invasive device called the laparoscope would not work. In fact, Westcott himself had first planted doubt in my mind about the effectiveness of the laparoscope the first time I met with him in May. At that meeting, he raised the possibility that the mass, then the size of an olive, might be too small to find using the narrow pointed laparoscope.

Just One Night in Hospital

Now that the procedure is behind me, I’m glad to report that in fact the laparoscope did work. Because it did work, my recovery was quick. In fact, I only spent one night in the hospital –Wake Forest Baptist Hospital, that is. At first, I was shaky and needed to be very careful when I attempted to stand, but the fact is that I was able to stand on my own within about an hour of being moved from the recovery area to a regular hospital room.

On my shaved stomach three small incisions are in evidence. The largest of these—lower left—is just a little more than an inch in length. I assume that this was the entrance point for the initial scope, the fixture for the light source and video camera that are key to carrying out this kind of surgery. I’m thinking that the gas used to inflate the abdominal cavity was introduced using a tube through one of the other two incisions and that the third incision was used for the tool containing the extraction device for removing parts of the mass.

Two Samples Extracted

In laparoscopic surgery, the abdominal cavity is filled with a gas to force organs away from each other so that the surgical team can get a better view of the organs. As for the extraction, the goal of the team was the preparation of samples to present to the pathologists. In my case, two samples were extracted. Together the two samples added up to a large part of the mass itself—this according to an assistant surgeon who spoke to me the day after the procedure.

What are the results? I don’t know at this point. The chief surgeon told my wife that he thought what he was seeing through the laparoscope was evidence of the return of lymphoma, but he acknowledged that he could not be sure and that no one could be sure without detailed pathology studies. And so why am I not including the results in this posting? Am I being coy?

No Preliminary Pathology Report

Herein lies the most disappointing part of the whole story. Harriet and I had been led to believe that we would be presented with a preliminary pathology report at the time of the laparoscopy itself, but that didn’t happen. The surgeon gave my wife his supposition from his observation, but that is as much as we got. The pathology report is still awaited. In the next posting I will be reporting on its findings.

As I’ve indicated, I made a rapid recovery from the procedure. Only one night in the hospital after abdominal surgery—that’s pretty impressive, I think. The value of minimally invasive surgery is hard to dispute, but I would be remiss if I did not make clear that this surgery was not without its side effects. I had three. Two of the three were related to the process of being sedated for a period of three hours. The third was the result of taking a particular painkiller and also the discomfort to be expected from abdominal surgery of any kind. Two of the three had to do with elimination functions. The other had to do with having a breathing tube stuck down my throat.

One last observation. I found it very interesting how the incisions from laparoscopic surgery are put back together. No stitches. No staples. Surgeons are now using Superglue to close up such wounds. Anyway that’s what one of the nurses told us, and it explains why my small incisions are so bright and shiny. Superglue for surgery—that amazes me.

To reach the author of Mind Check, write Stephen.saft@gmail.com.

Copyright © 2007 by Stephen Alan Saft