HOSPITAL PRACTICE

New targets, new drugs highlight oncology meeting

The spotlight at this year's meeting of the American Society of Clinical Oncology (ASCO) may have been on ST1571 (Gleevec, Novartis; see "There's new hope for some leukemia patients"), but other hot issues were also discussed.

The San Francisco meeting attracted 25,000 oncologists and other health professionals from around the world. The good news had to do not only with promising results from new kinds of therapeutics, such as monoclonal antibodies (MAbs) that target the epidermal growth factor receptors on tumors and angiogenesis inhibitors, but also better drug combinations.

A phase I clinical trial of EntreMed's angiostatin inhibitor endostatin, reported by Roy Herbst, M.D., et al., at the University of Texas M. D. Anderson Cancer Center, Houston, concluded that there were no dose-limiting toxicities with the drug, and there may have been some tumor responses. Future trials, he said, will seek to achieve more sustained plasma levels and to use the agent in combination with radiation therapy, chemotherapy, and biological agents.

In his plenary address, ASCO president Lawrence Einhorn, M.D., Distinguished Professor of Medicine, Indiana University, Indianapolis, hailed the new genomic era that provides new targets for the development of hopefully less toxic as well as more effective anti-cancer agents. He called the research being presented at this year's ASCO meeting "elegant and eloquent" and added that "the enthusiasm from molecular-targeted therapy has been justified." What follows are some of the major findings reported at the meeting.

Cancers react to new MAb. A new chimeric monoclonal antibody, cetuximab (IMC-C225, ImClone Systems), that binds selectively to epidermal growth factor receptors (EGFRs) showed activity in some patients with advanced colorectal cancer who were no longer responding to standard treatment with irinotecan (Camptosar, Pharmacia Corp.) and fluorouracil (5-FU), according to Leonard Saltz, M.D., associate attending phy-sician at Memorial Sloan-Kettering Cancer Center in New York City. He said that in 121 patients whose disease was progressing, the irinotecan was continued with the addition of cetuximab, and 27 patients responded with a more than 50% reduction in tumor size. "Now that we have shown that responses can be achieved in these resistant patients, we are excited about the possibility of using it in conjunction with first-line therapy."

In another study, led by James Abbruzzese, M.D., of M.D. Anderson Cancer Center, five of 40 patients with advanced pancreatic cancer showed partial responses to a com-bination of cetuximab and gemcitabine (Gemzar, Lilly). In addition, 16 patients who received the combination had either minor responses or stabilized disease. Abbruzzese said a larger trial will be needed to demonstrate how this combination might affect survival. In a separate study at the same institution, prinicipal investigator Herbst found that of the 63 head and neck cancer patients re-ceiving both the IMC-C225 and chemotherapy, 20% responded. He said that squamous cell carcinoma of the head and neck should respond especially well to this type of therapy, because these cancers have many epidermal growth factor receptors.

Also in the category of epidermal growth factor inhibitors is the oral drug ZD 1839 (Iressa, AstraZeneca), which is an orally selective epidermal growth factor-tyrosine kinase inhibitor.

Iressa has been shown to have promising activity, and to be well tolerated as adjuvant therapy, in phase I studies of various cancers, particularly nonsmall-cell lung cancer. In a study sponsored by the National Cancer Center in Tokyo, five of 23 patients who had nonsmall-cell lung cancer showed partial responses, and phase II and III trials of Iressa for this disease are under way.

Lung cancer responds. An investigational antisense compound, ISIS 3521 (Isis Pharmaceu-ticals), continues to show strong responses and demonstrate prolonged survival and time to progression of disease in patients with advanced non-small-cell lung cancer (NSCLC). Of the 48 patients in the trial to date, one has experienced a complete response and 21 a partial response, according to Alan Yuen, M.D., assistant professor of medicine at Stanford University.

In a study by the Southwest Oncology Group (SWOG), San Antonio, the longest survival yet for stage IIIB NSCLC patients was reported when docetaxel (Taxotere, Aventis) was given after standard chemotherapy with cisplatin/etoposide along with radiotherapy. Laurie Gaspar, M.D., SWOG lung committee radiation oncology cochair, said 40% of patients remained alive at three years, while a prior SWOG study documented a 17% three-year survival rate.

Jean McCann

Based in Ohio, the author has extensive experience covering national and international medical and pharmaceutical meetings and is a clinical contributor to Drug Topics.

Jean Mccann. New targets, new drugs highlight oncology meeting.

Drug Topics

2001;11:27.