Comparing Chemotherapy with Radioummunotherapy

For decades chemotherapy has been the primary cancer treatment. In this entry I'll take a cursory look at both chemo and one of its emerging competitors, radioimmunotherapy.

Chemotherapy

Chemotherapy is the use of chemicals (chemical+therapy = chemotherapy) to inhibit cell division and encourage cell death. Although the earliest uses were in the 1940s, the real breakthrough occurred in the 1960s and combination chemotherapy.

Combination chemotherapy

In the mid 1960s researchers, who had learned to treat tuberculosis by attacking it with a combination of drugs all at once, each with a different mode of attack so that even if the TB developed a resistance to one drug, it couldn't possibly survive them all, decided to apply this principle to cancer treatment.

Enter combination chemotherapy—receiving an array of chemo drugs, 8 or more in some cases. The system revolutionized treatment, as chemo drugs with varying methods of preventing a cell from dividing and growing, proved effective at treating tumors and cancerous cells. But it wasn't—isn't—perfect, by any stretch. For instance:

• Chemo drugs are non-specific. Indiscriminate. They practice a scorched-earth policy in your tissues, inhibiting the division of cancer cells AND healthy cells (especially fast-growing ones like those in your hair follicles, which is why it often falls out);
• Killing healthy cells and tissue can make you especially sick. It can be fatal. And irony of ironies, it can also be carcinogenic, leading to secondary cancers later in life;;
• Chemo is administered in lengthy regimens, sometimes requiring as many as six months or more to complete, and they can be extraordinarily toxic, causing a host of problems in other parts of the body.

Often, combination chemotherapy is further combined with radiation therapy. Like chemo, radiation is non-specific; it cooks everything in its path, cancerous or not.

Radioimmunotherapy

While chemotherapy and radiation therapy are something akin to carpet-bombing, radioimmunotherapy (RIT) resembles a surgical strike. Whereas chemotherapy and radiation commit unsophisticated cell slaughter, radioimmunotherapy is cellular murder-for-hire, sending armed, trained assassins into a civilian population looking only for certain target cells.

Radioimmunotherapy is an aspect of biological anti-cancer therapy that combines chemo's ability to inhibit cell growth with radiation's ability to make cells commit suicide. Radioactive molecules are attached to drugs called monoclonal antibodies and injected into the body where they seek out and attach to cancer cells preventing their replication and killing them while limiting damage to healthy cells.

In the treatment of B-cell non-Hodgkin's lymphomas, they do this by checking the surface of white blood cells looking for a protein called CD20. When they find it, they know that this white blood cell is a B-cell.

Two such drugs are currently approved for treatment in the U.S.: Ibritumomab tiuxetan (Zevalin®) and tositumomab (Bexxar®).

Ibritumomab tiuxetan (Zevalin)

Zevalin is a monoclonal antibody with the same CD20-seeking properties as Bexxar. However, Zevalin takes the precision to a new level by using the monoclonal antibody with two different radioisotopes. First, indium-111 is attached to Zevalin and injected into the body so that doctors can perform an imaging scan and see that the distribution in the body is acceptable. Then yttrium-90 is attached to Zevalin and injected into the body as Y-90 Zevalin. The Zevalin binds to the CD20 surface protein of B-cells, allowing a dose of the yttrium-90 radiation to kill the cell.

Tositumomab (Bexxar)

Bexxar is a mix of monoclonal antibodies armed with the ability to spot the CD20 molecule on the surface of B-cells. Once there, it binds to the cell and puts in a call to the immune system, which either kills the cell or prevents it from growing. Some of these antibodies (131I-tositumomab) are also carrying the radioactive substance iodine-131, which delivers a dose of radiation directly to the B-cell.

Unlike conventional chemotherapy, radioimmunotherapy lasts less than two weeks and toxic exposure is kept to a minimum.

Chemo vs RIT

To paraphrase Newton, if radioimmunotherapy does in fact prove to be the future king of anti-cancer therapy, it is only because it has stood on the shoulders of past treatments.

Arguably, RIT is the future of anti-cancer therapy because of its promise to limit the damage to healthy tissue that is so closely associated with chemo and radiation. But it is still young. We don't know what the long-term effects of some of these drugs might be on the body, if any. But this is the history of cancer treatment: we go with what works today, because if it works today that it means it works at all, and is therefore more effective than any other alternative.

Since the 1940s chemotherapy has been a life-saver, a giant of a presence in the cancer community. It has also offered us an ideal lens through which to view and understand the true nature of cancer, a disease that betrays the body into participating in its own death.

Additional Resources

• Zevalin site
• Zevalin Treatment Locator
• A Closer Look at the Zevalin Regimen