NEW YORK--Patients with stage III colon cancer are being sought for a clinical trial newly underway to determine whether the monoclonal antibody (MoAb) 17-1A is an effective adjuvant in combination with 5-fluorouracil (5-FU) plus levamisole(Drug information on levamisole), said Richard Pazdur, MD, associate professor of medicine, M.D. Anderson Cancer Center.
Speaking at the 13th annual symposium of the Chemotherapy Foundation, Dr. Pazdur described the new MoAb (Panorex, from Glaxo Wellcome) as a murine form of the IgG-2a MoAb 17-1A, which recognizes a cell-surface glycoprotein preferentially expressed in adenocar-cinomas. The 17-1A antibody has been shown in vitro to mediate antibody-dependent cell cytotoxicity and complement-mediated cytolysis.
MoAb 17-1A has been approved for single-agent adjuvant therapy in Germany, where a clinical trial showed significant reductions in disease recurrence and cancer-related deaths. The most common adverse events were diarrhea, abdominal pain, and nausea and vomiting.
Other adverse events included fever, chills, malaise, dizziness, fatigue, headache, hot flushes, increased sweating, and hair loss. There were no toxicity-related hospitalizations and no therapy-related deaths. There were five severe anaphylactoid reactions, possibly due to human antimouse antigen (HAMA) response.
Dr. Pazdur said that the ongoing US trial is studying 17-1A in combination with 5-FU plus levamisole, currently the most widely used postoperative adjuvant therapy for stage III colon cancer.
Compared with surgery alone, 5-FU plus levamisole produces a 41% reduction in the risk of recurrence and a 33% reduction in overall mortality, Dr. Pazdur said. The rationale for adding the MoAb, he explained, is the complementary action and nonadditive toxicity profiles of the two therapies.
The trial expects to enroll 1,800 patients over an 18-month period. Patients receive either 5-FU plus levamisole beginning 22 to 28 days postoperatively according to the schedule used in prior clinical trials, or 5-FU/levamisole and 500 mg of 17-1A intravenously beginning 15 to 21 days postoperatively, followed by 100 mg doses every 4 weeks for 4 additional weeks. Based on previous trials, it is hoped that the lower monthly doses will result in weaker HAMA response.