New Test May Predict Early Response to Chemotherapy

SAN FRANCISCO—An investigational test kit (Apomate) to measure apoptosis may be able to detect a positive or negative response to chemotherapy within just a few days of initiation of treatment, allowing nonresponders to switch quickly to a different treatment.

Neil D. Steinmetz, MD, vice president and medical director of the Theseus Imaging division of North American Scientific, Inc., Boston, the developer of Apomate, presented the study results at the 93rd Annual Meeting of the American Association for Cancer Research (abstract 4136).

Apomate is a kit for the preparation of technetium (Tc-99m)-labeled recombinant human annexin V, a 35-kD protein that binds to phophatidyl-serine, which is expressed on the surface of cancer cells during the early stages of apoptosis. Tc-99m releases a signal that can be visualized using scintigraphic imaging. "Thus, the Apomate scan can be thought of as a method that allows us to image dying cells in living patients," Dr. Steinmetz said.

Apomate is administered via intravenous injection before initiation of chemotherapy, and scintigrams are taken a few hours later to determine baseline levels of spontaneous apoptosis. Apomate is again injected 1 to 3 days after the first chemotherapy dose. An increase in Apomate uptake during the second scan, compared with baseline, is considered a positive response. Study patients continue with their clinical treatment, and their long-term response to chemotherapy is later compared with the results from Apomate scintigraphy.

Preliminary phase I/II results obtained from patients enrolled at centers in the United States and Europe have been positive, Dr. Steinmetz said.

In one study of patients with non-small-cell lung cancer, initial results were available from 13 patients enrolled at five centers. Five patients had positive Apo-mate scans indicating increased apoptosis over baseline. Of these five patients, three had responded to chemotherapy and two had stable disease. Of the remaining eight patients who did not demonstrate a positive Apomate response, six had either died or had progressive disease, and two had stable disease.

In another study of 15 subjects with breast cancer, lung cancer, or lymphoma, Apomate scan results were compared with outcomes up to 1 year after the initiation of chemotherapy. All seven of the patients who responded to chemotherapy (three partial responses and four complete responses) had a positive Apomate result. In contrast, none of the eight nonresponders had a positive Apomate test, and six of these patients have died or experienced progressive disease (P < .01).

"These studies demonstrate that apop-tosis in untreated and treated human tumors can be detected in vivo using noninvasive Apomate scintigraphy," Dr. Steinmetz concluded. "Initial study results demonstrate an increase in Apomate localization, suggesting increased apopto-sis or necrosis, in some tumors within hours after the initial course of chemotherapy, and this increase in localization correlates with increased rates of objective response and survival time."

The researchers are planning to continue studying the use of Apomate in larger numbers of patients being treated for lung cancer and lymphoma. Other studies investigating the effectiveness of a second-generation formulation are also in the works.