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Melanoma Vaccine with Three Cell Lines Linked to Increased Survival: Presented at AACR

By Paula Moyer

ANAHEIM, CA -- April 25, 2005 -- A melanoma vaccine consisting of three lethally irradiated cell lines (Vaccimel) is well tolerated and appears to prolong disease-free survival, according to investigators who presented findings here April 18^th at the 96^th annual meeting of the American Association for Cancer Research.

The investigators, who had obtained early promising results with the vaccine, focused their current study on using the vaccine along with a treatment designed to facilitate the formation of recombinant human granulocyte macrophage colony stimulating factor (rhGM-CSF).

"Our findings showed that the vaccine should be used in the early stages of melanoma, because we got better results on those patients," said principal investigator José Mordoh, MD, professor of oncology, Alexander Fleming Institute, University of Buenos Aires, Buenos Aires, Argentina. "We have proven, though, that the combination of the vaccine and colony stimulating factor produces very good results in patients with Stage III disease. Therefore, we are going forward with Phase II trials that include the vaccine and the colony stimulating factor."

The investigators wanted to see if adding the colony stimulating factor would increase the immune response in vaccinated patients with melanoma. They conducted a phase 1 clinical trial combining the two modalities in nine men and 11 women with stage IIB, III and IV disease. The patients ranged in age from 15 to 67 years.

The vaccine was administered intradermally four times every 3 weeks at a dose of 15 x10⁶ irradiated cells per dose. The vaccine doses included Bacille Calmette Guerin (BCG), which was used as an adjuvant.

To test the colony-stimulating factor, the investigators divided the patients into five cohorts of four patients. One group received placebo; the remaining four received rhGM-CSF at a total dose of 150 mcg, 300 mcg, 400 mcg or 600 mcg, respectively. These doses were divided into four daily doses that were given on the first vaccination day of each vaccination cycle.

One patient had progression of disease and therefore withdrew from the study. The most frequent toxicities were as follows: five patients had grade 1 fever; nine patients had grade 1 asthenia; six patients had grade 1 headache; five had grade 1 thoracic pain; and nine had grade 1 myalgia. All of the 19 continuing patients had grade 2 local toxicity. No patient had toxicity of grade 3 or more, Dr. Mordoh explained.

The results show that the most effective dose of adjunctive rhGM-CSF was between 300 mcg and 400 mcg, since three of the four patients who received the 600 mcg dose had grade 1 thoracic pain, and two of them experienced grade 1 abdominal pain. Although the BCG dose had to be reduced in five patients, no patients had to reduce their dose of rhGM-CSF.

The cellular immune response, known as delayed type hypersensitivity, was highest in patients who received at least 400 mcg of rhGM-CSF. Although there was an increase in humoral response to BCG, especially at the higher doses; there was no humoral response to the vaccine.

The level of suppressor T cells CD4+ and CD25+ were unrelated to patient outcome, Dr. Mordoh said. However, some excised subcutaneous metastases showed heavy infiltration by CD8+ T cells.

After a median of 25 months of follow-up, all patients with stage IIB disease were alive and disease-free. The disease-free survival rates were 66.7% for stage III patients and 22.2 % for stage IV patients.

The researchers concluded that Vaccimel plus rhGM-CSF is a non-toxic treatment, and that the 400 mcg dose of rhGM-CSF appears to be the most suitable to increase immune cellular responses.


[Presentation title: Phase I Clinical Trial of VACCIMEL Plus GM-CSF in Melanoma Patients Stages IIB, III and IV. Abstract 3460]

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