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New Treatments for Colon Cancer and Rectal Cancer

Worldwide, colorectal cancer is one of the most common causes of death from cancer, and there are 300,000 cases in the United States and Western Europe. Adjuvant treatments that reduce the mortality can be cost effective, even if colon cancer, colorectal cancer, rectal cancer, cancer of the colon, cancer of the rectum.

Levamisole was the early drug. There were some studies in advanced disease however with 5FU plus levamisole, an entirely empiric combination of a drug and an immuno-modulatory agent that suggested benefit in advanced colorectal cancer and it led the Mayo Clinic group to start this trial in 1978. It was a randomized prospective trial in 400 patients with high-risk resected.

In 1984 the first intergroup trial was done, and this was actually two separate trials. The false-positive results from the small North Central Group trial was that levamisole as a single agent had any activity at all. You can see that here, the overall survival is identical.

The issue of leucovorin arose in the 1980s so just as we were getting comfortable doing 5FU levamisole, the issue arose based on the meta-analysis of 5FU leucovorin versus 5FU alone, as to what this more intensive regimen might accomplish in the adjuvant setting. So there were three. This is the industrial era. These were three very large trials that were begun.

The other treatment is a non-chemotherapeutic approach. It’s an immunologic approach using Panorex or monoclonal antibody 17-1A. This is a murine monoclone. It recognizes surface glycoproteins on both cancer and normal cells. In the laboratory it induces antibody-dependent cytotoxicity. In the advanced disease models that we typically use in our clinic.

There are two trials are ongoing in the United States. The first one is an intergroup trial comparing the continuous infusion 5FU to this three-drug, six months 5FU, leucovorin, levamisole regimen. The other study is a translation of the portal vein infusion trial because when you do portal vein infusions you don’t necessarily see reduction in liver metastases.

The current best practice in adjuvant treatment of colon cancer is 5FU, leucovorin and levamisole for 6-8 months. PVI and Panorex are still in the uncertain category. Infusional fluorouracil and the oral counterpart are still pending and are at least as good or a little bit better, in terms of tolerability, than bolus therapy. The Tomudex is a specific thymidylate synthase.

PVI 5FU. This was given at 225 mg per meter squared daily by infusion throughout the radiation, and what this showed was a 10% survival advantage for the group that got the PVI versus bolus. This is the correct way of giving chemotherapy and radiation together. Although in practice many people will give 5 FU and leucovorin.

So what is the future for rectal cancer? Currently the answer is chemo-radiation. But do all high-risk patients need both radiation and chemotherapy? If someone has a T3 N0 tumor with less than a 5% chance of local regional failure, do we need to treat 100 patients with pelvic RT to save one from local failure? I hope not. I think with the integration of new drugs, with more intensive chemotherapy, I can envision a trial of chemotherapy alone versus chemo-radiation, especially looking at the low risk population. I think the sequencing of surgery versus pre-op versus post-op is extremely important. So where should we be going? I think the answer is we