Chemoimmunotherapy May Boost Melanoma Response Rates

BUFFALO, NY--Early studies comparing the combination of chemotherapy and immunotherapy with traditional chemotherapy alone suggest that the combination may improve immune responses in patients with metastatic melanoma, said Thomas Olencki, DO, Department of Hematology/Medical Oncology, Cleveland Clinic Foundation.

"We have data from a study that show an increase in complete response rates by patients who received the combination chemoimmunologic approach, but the number of patients overall was not large. We are hopeful that future studies will back up this initial observation," Dr. Olencki said at the first meeting of the Regional Cancer Center Consortium for Biological Therapy of Cancer, hosted by Roswell Park Cancer Institute.

Patients who present with metastatic melanoma have an average survival of 6 to 9 months after diagnosis. These patients can be grouped into two classes: M1A patients who have low-bulk disease involving the skin, subcutaneous tissue, lymph nodes, and lungs; and M2A patients who have metastases to the liver, bone, and brain.

While some patients diagnosed with metastatic melanoma have survived to the 5-year mark, these patients are generally from the M1A class, and it is unclear why certain patients respond better to treatment.

"We need a randomized trial to make sure that we are not in some way choosing the ‘best’ patients for our drug trials," Dr. Olencki said. "History has shown that some patients will survive for several years regardless of the type of therapy they receive. The data show such a small improvement overall, that we need to verify that the improvement is real and not a factor of selection."

The most active chemotherapy drug in metastatic melanoma, and the only one with FDA approval for this indication, is dacarbazine (DTIC), Dr. Olencki said. Used alone, it has a 20% partial response rate and a 1.5% long-term complete response rate, with the M1A patients showing the greatest response. The median duration of response is 3 to 6 months. The addition of other chemotherapy drugs may not improve these results, he said.

Metaanalysis Results

In a metaanalysis presented at the 1997 ASCO meeting, 266 metastatic melanoma patients were treated with high-dose bolus recombinant interleukin-2 (rIL-2) (three times a day on days 1 to 5 and 15 to 19). This therapy showed a 17% overall response rate, with a median duration of 6.5 months. Ten of the 266 patients (3.75%) remain in complete response. "While this doubles the previous best of 1.4% seen with chemotherapy alone, these numbers are still very small," he said.

Initial studies of patients receiving a combination of chemotherapy, rIL-2, and interferon showed response rates between 33% and 60%, with a median duration of response ranging from 5 to 24 months.

"Unfortunately, the long-term survival rate in this group of chemoimmunother-apy patients is not statistically different from that of rIL-2 alone," he said. "Thus, there is a pressing need to complete the Intergroup study E3695, which randomizes patients between chemotherapy and chemoimmunotherapy."