Sugen drug "surprisingly effective" in early trials

European study finds it works in about 25 percent of patients

   The new cancer drug from Sugen has proven surprisingly effective in early clinical trials, dramatically shrinking tumors in 25 percent of patients.
   Preliminary results from a phase I trial at France’s biggest cancer center, Institut Gustave Roussy in Villejuif, were presented at the 14th EORTCNCI- AACR cancer symposium held Nov. 19-22 in Frankfurt, Germany. The symposium was jointly sponsored by the European Organization for Research and Treatment of Cancer, the U.S. National Cancer Institute and the American Association for Cancer Research.
   The oral cancer drug SU011248, which is given in capsule form, is a signal transduction inhibitor designed to act against several abnormally behaving enzymes along the cellular signaling pathway. SU011248 was developed by Sugen, a California-based company that was acquired in 1999 by Pharmacia.
   Patients in the study had a range of advanced cancers, including renal, non small-cell lung, neuro-endocrine, uterine, angiosarcoma, mesothelioma, pancreatic, breast, colorectal and nasopharyngeal. Patients had failed to respond to all other therapies: in many cases at least three different types of treatment had been tried.
   “Any activity in this situation is very promising since everything else has failed,” said lead researcher Dr. Eric Raymond. “But we did not expect to see such a high number of responses in a range of cancers.” A response was defined as a tumor reduction of more than 50 percent as measured by CT scan.
   The goal of any phase I trial is to determine drug safety, not to measure the effectiveness of the drug. That patients responded well, Raymond said, “was huge. You are expecting in a phase I trial less than 5 percent response.”
   The drug is well tolerated by most patients. The dosage was increased for some patients, and patients became more fatigued the greater the dose.
   The drug also drained the color from patients’ hair, and some patients’ skin turned a “tanned gold” from the drug. This effect wore off within a week of stopping treatment.
Raymond said that the phase I study would continue for the next six months or so. Phase II and III studies would start immediately afterwards and would include a formal analysis of the response rate — an analysis that was inappropriate for the phase I study, which began with very low doses of the drug.
   Jerry McMahon, president of Sugen, said there were a half dozen phase I trials underway and all are producing similar results — including patients with GIST, gastrointestinal stromal tumor. More data will be presented at the American Society for Clinical Oncology conference next year.
   The drug is a newcomer in the field of anti-angiogenics — drugs designed to damage tumors by attacking the blood vessels that feed them. Although it has been a major research field over the last decade or more, angiogenesis has not so far lived up clinically to its early research promise. But, the response in this study provides evidence that anti-angiogenics may yet have a future.
   Added Raymond: “Initially we thought that the drug would be an angiostatic agent that stabilises tumors, rather than an angiotoxic agent that actively shrinks tumors. Angiostatic compounds were associated with a low level of response, but angiotoxics are much more promising in inducing responses.
   “We were happily surprised right from the first patient response — a reduction of more than 50 percent in the tumor for six months in someone with a renal cancer that had recurred and who also had adrenal and lung secondaries that had not responded to immunotherapy.”
   Dr. Jaap Verweij, chairman of the meeting’s scientific committee, noted that he’s “seen a lot of phase I trials in my life,” and called the results “fascinating. And the toxicity we will learn how to handle that, I am sure.”
   Raymond said that a lot more work needed to be done on dosing and on toxicity as the drug affected normal blood vessels as well as tumor vessels. It was also vital to get information on toxicity after repeated treatment cycles to avoid discovering late delayed cumulative side effects.
   He concluded that if the drug’s activity holds up in further trials, it has the potential to be a potent new weapon.
   “It is one of the first angiotoxic drugs with anti-tumor effects. In fact, we had too much effect in higher doses in some patients resulting in tumor necrosis that required surgery. So this drug is teaching us a lot about the potential efficacy and, just as important, about the adverse effects of new anti-angiogenic agents.”

From the ECORT Web site, Reuters Health News and MW Communications.