Oct. 12, 2005 - A personalized cancer vaccine extends survival for some late-stage melanoma patients, research shows.
Melanoma is very dangerous skin cancer. Advanced stage IV melanoma kills about 90% of patients within five years of diagnosis. Patients with advanced melanoma are advised to seek clinical trials of experimental treatments.
Now one of those trials seems to be helping the healthiest of stage IV melanoma patients. These so-called stage IV M1a patients are those whose tumors have spread just below the skin or to distant lymph nodes but haven't yet penetrated other organs.
The study tested a vaccine treatment -- Oncophage, from Antigenics Inc. -- in stage IV melanoma patients. Oncophage is made from a patient's own tumor cells. It stimulates powerful immune responses that attack tumor cells remaining in the body after surgery. Two out of three patients got the vaccine; the other third of patients got whatever current treatment their doctors thought best.
Antigenics released early results from the study this week. Oncophage, the company says, did not help patients whose melanoma already had spread to the lung (stage IV M1b) or to other organs (stage IV M1c).
It was a much better story for the stage IV M1a patients. These patients lived at least 50% longer than those in the doctors'-choice-of-treatment comparison group. The comparison group survived a median of 12.8 months. The M1a patients treated with Oncophage survived a median of 20.9 months.
That's exactly the patients one would expect to respond to a cancer vaccine, says researcher John M. Kirkwood, MD, director of the melanoma center at the University of Pittsburgh Cancer Institute. Kirkwood leads the melanoma committee of the Eastern Cooperative Oncology Group, one of the largest clinical cancer research organizations in the U.S.
"A quarter or so of patients with advanced melanoma have this manifestation of soft-skin-tissue disease that does not involve internal organs," Kirkwood tells WebMD. "In that group we saw the impact of this vaccine."
Earlier Treatment, Better Results?
Based on these findings, Antigenics is designing a new clinical trial to target stage IV M1a patients. The new trial may also include patients with earlier-stage disease whose melanomas have been completely removed by surgery.
Such patients -- who run a high risk of having their cancer come back -- may be the ones who benefit most from Oncophage.
"The most rational application of this and all cancer-vaccine modalities will be the use of this vaccine for surgically treated patients who do not have any tumor remaining at all," Kirkwood says.
That may very well turn out to be the case, says Garo Armen, PhD, Antigenics Inc. chairman and CEO.
"If we can make a fundamental improvement in melanoma treatment, it would be terrific," Armen tells WebMD. "It is our opinion that Oncophage would be most effective in patients who are slightly earlier in the course of disease than traditional end-stage patients. This particular trial gives us an indication of that. We tested the vaccine in late-stage melanoma, in patients with an expected survival of six to 12 months -- but the healthier patients did much better. That is pretty much as our scientific information has told us it should be."
As a melanoma vaccine, Oncophage is still experimental. The next clinical trial -- the one on which FDA approval would depend -- is still in the planning stages.
However, since Oncophage is made from a patient's own tumor cells, it can be used in nearly any kind of cancer. The only limiting factor, Armen and Kirkwood say, is whether there is enough tumor to make the vaccine. About 3 to 7 grams are needed, as multiple injections work better than just a few.
A clinical trial in patients with late-stage kidney cancer is drawing to a close. If the vaccine works in these patients -- and earlier trials suggest that it may -- the trial could be used to apply for FDA approval.
How Oncophage Works
Oncophage takes advantage of a sticky kind of protein called a heat shock protein or HSP. The body is full of HSPs. HSPs do a lot of things. One thing they do is to chaperone cellular proteins by helping them form correctly and moving them from one place to another.
When a diseased cell dies, HSPs carry little snips of the dead cell's proteins to the immune system. Some of these protein snips are antigens that help the immune system seek out and destroy other cells with the same disease.
To make Oncophage, Antigenics takes tumor cells removed from a patient and breaks them open. HSPs carrying tumor antigens are removed and used to make the vaccine.
Making an individualized vaccine isn't cheap. Antigenics thinks a course of treatment will cost $10,000 to $20,000.