Getting intimate with Velcade (Bortezomib)

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Hello readers,
Velcade seems to be the big kahuna drug on the streets of Multiple Myeloma these days. Today I got really curious about it. What is it? How does Velcade work? What are the side effects? Is it safe?

We had written a blog about the clinical relevance of Velcade, but I wanted to write more about the biochemistry involved.

So, what is Velcade anyways?

Velcade Molecule

Velcade also known as Bortezomib is manufactured by Millenium Pharmaceuticals. It used to be called PS-341 in its younger days when it was only in clinical trials. It is an antineoplastic agent. Did you guys know that Velcade is actually a combination of three proteins? Pyrazinoic acid, phenylalanine and Leucine with boronic acid instead of a carboxylic acid. Turns out the boron atom plays a key role as it binds to the catalytic site of the 26S proteasome. What the heck is that?

The 26S proteasome is a massive protein complex that can be thought of as a cellular recycling truck and recycling plant all rolled into one. It lumbers along the cell and when an incorrectly folded protein or a broken protein is labeled with ubiquitin, (a kind of tag identifying these derelict proteins as garbage) the proteasome binds to the ubiquitin, and degrades the proteins with proteases and recycles the components for future proteins.

Velcade is kind of like an impostor molecule that fools the proteasome into thinking it is garbage that needs to be recycled. And it fools it so good that it shuts the proteasome down for business. That boron atom holds onto the catalytic site of the proteasome and does not let go. In essence, when velcade is administered, the recycling mechanism that goes on in cells is severely compromised or shut off. Defunct proteins pile up in the cell and the cell eventually dies.

Now, what allows Velcade to target multiple myeloma cells, as opposed to healthy ones?

Well, it turns out this is not totally clear. Myeloma plasma cells are much more sensitive to proteasome inhibition than healthy cells. Healthy cells are also affected, but side effects are much less than those seen when people take regular chemo. This proves that not all things in science are clear, it is observed that something works better but the exact mechanism behind Velcade’s success still merits more research.

So what are the side effects of Velcade?

The following have been observed in 30% or more of people who take Velcade

Blood counts are affected. Many of the most common side effects of Velcade affect blood cell counts in the body, such as:
- Thrombocytopenia (low numbers of platelets)
- Neutropenia (low numbers of neutrophils, a type of white blood cell)
- Anemia (low numbers of red blood cells)

Peripheral neuropathy, felt as a burning, tingling, or numbness in the hands or feet, occurs in approximately 30 percent of patients.
- The peripheral neuropathy can at times be painful, and this may be worse in patients with pre-existing neuropathy.
Nausea
Diarrhea, or constipation
Fatigue or weakness
Loss of appetite
Fever

The following have been observed in about 10 – 29% of patients taking Velcade.

Headache
Difficulty sleeping (Insomnia)
Joint pains, arthralgia, myalgias
Swelling of the face, hands, feet or legs (edema).
Low white blood cell count. (This can put you at increased risk for infection.)
Shortness of breath
Dizziness
Rash (see skin reactions)
Dehydration
Upper respiratory tract infection
Cough
Bone pain
Anxiety
Muscle cramps
Heartburn
Abdominal pain
Low blood pressure
Itching
Blurring of vision
Blood test abnormalities: (low sodium, low magnesium, low calcium, low potassium).

There are other rarer side effect with probably include things like shock, death, internal bleeding — scary stuff that happens in less than 10% of all cases. I had a hard time finding those listed anywhere.

When and how is Velcade given?

Velcade is administered via injection into the blood stream, and was initially approved for the treatment of relapsed and refractory myeloma in 2003, then for relapsed patients in 2005, and most recently was approved for previously untreated patients (also referred to as “first-line”) in June 2008. Velcade is now approved for use in myeloma in over 90 countries worldwide. ^[1]

Velcade being injected

Velcade

Anyways, there you have it. Hope this was informative and enjoyable. And yes, feel free to use our Patient Navigator to Find Velcade Myeloma Clinical Trials