SAN FRANCISCOIn an effort to extend the activity of gemcitabine(Drug information on gemcitabine) (Gemzar) against pancreatic cancer, researchers have paired an investigational chimeric monoclonal antibody, IMC-C225 (cetuximab) with the standard chemotherapy. IMC-C225 selectively binds to epidermal growth factor receptor (EGFR).
How IMC-C225 Works
Growth factors EGF and TGF-alpha bind to EGF receptor (EGFR) and activate the EGFR pathway, which is involved in tumor growth, repair, angiogenenesis, and metastases. IMC-C225 binds to EGFR and blocks the ability of these growth factors to signal the tumor cell. IMC-C225 leads to the internalization of EGFR, preventing future receptor activation.
The phase II trial, involving 40 patients, produced a 1-year overall survival rate of 32.5% and an increase in time to progression from 2 months for historical controls to almost 4 months.
James Abbruzzese, MD, chairman, Department of Gastrointestinal Medical Oncology, M.D. Anderson Cancer Center, reported the results at the 37th Annual Meeting of the American Society of Clinical Oncology (ASCO abstract 518).
"This work explores the value of targeting specific molecules and proteins intimately associated with the growth of pancreatic cancer cells," Dr. Abbruzzese said. "In this case, we looked at targeting EGFR, known to be important in pancreatic cancer growth." Of the 54 patients screened for the study, more than 90% tested positive for EGFR expression, a condition for acceptance into the trial.
Compared with historical controls receiving gemcitabine alone, combining IMC-C225 and gemcitabine more than doubled the response rate, from 6% to 13%, Dr. Abbruzzese said. At the 1-year point, 32.5% of patients were still alive with this combined treatment, compared with 18% to 20% of historical control patients receiving gemcitabine alone.
The most common adverse reactions reported during the study were nausea, fatigue, and an acne-like rash.
"It looks promising at this point," Dr. Abbruzzese said. "But we have to confirm it in a larger randomized study." He said that a larger study is under discussion with the sponsoring company, ImClone Systems Incorporated. "There’s no written protocol yet," he said, "but we have discussed how it would be designed and who would be involved. I’m hoping this will move along quickly so that we have a study ready to go by the third or fourth quarter of this year."