From Our 2007 Archives

Targeted Cancer Therapies Continue to Impress

By Amanda Gardner
HealthDay Reporter

SATURDAY, June 2 (HealthDay News) -- Small scientific steps are making headway against various cancers, many of which are historically difficult to treat.

Two much-watched drugs of the past year, Sprycel and Avastin, are again showing good results in new trials, according to research presented Saturday at the American Society of Clinical Oncology (ASCO) annual meeting, in Chicago.

"Molecular targeted therapies that were developed a few years ago are being expanded dramatically in scope," said Dr. Robert F. Ozols, senior vice president of the medical science division at Fox Chase Cancer Center in Philadelphia and chairman of ASCO's communications committee.

"These are incremental advances, but they're important," added Dr. Len Lichtenfeld, deputy chief medical officer for the American Cancer Society. "I don't see anything in the plenary session or any other special session that stands out as a major breakthrough. We've come to a time when these advances are becoming routine, and that's a good thing."

Preliminary findings from a phase II trial of Sprycel (dasatinib) found high response rates to the drug when used in newly diagnosed patients with chronic myelogenous leukemia (CML).

The drug is currently approved as a second-line treatment for CML in patients who have developed resistance to Gleevec (imatinib), the standard first-line treatment. Both drugs are targeted therapies.

After three months, 81 percent of patients taking Sprycel had a complete hematologic response, meaning normal blood counts and no enlargement of the spleen. Seventy-three percent of patients had complete cytogenetic response, meaning no evidence of the "Philadelphia chromosome," which harbors the abnormality responsible for the disease. After six months, 95 percent had complete cytogenetic response, the trial found.

In previous studies, 54 percent of patients receiving a lower dose of Gleevec and 85 percent of those receiving a higher dose had complete cytogenetic response. The results of the two studies cannot be directly compared, however, because the Sprycel results are so preliminary.

A second study found that adding Avastin (bevacizumab) to interferon alpha-2-a as a first-line treatment for advanced kidney cancer nearly doubled progression-free survival, from 5.4 months to 10.2 months. It's not yet known if overall survival will be better with Avastin.

Avastin, an anti-angiogenesis drug that inhibits blood supply to tumors, is already approved to treat colorectal and non-small cell lung cancers. A study presented earlier Saturday found that, for the first time, adding Avastin to treatment of patients with advanced non-small cell lung cancer slowed the growth of the cancer.

People with kidney cancers have few treatment options, although recently two targeted therapies have recently been approved: Nexavar (sorafenib) and Sutent (sunitinib).

Adding arsenic trioxide to standard therapy resulted in survival improvements in patients with acute promyelocytic leukemia (APL), a rare form of leukemia. Arsenic trioxide is already used as a second-line, but not first-line, treatment for APL.

The compound, a poison, is used in traditional Chinese medicine.

After three years of study in more than 500 adults, overall survival among those taking arsenic trioxide was 86 percent, compared with 77 percent in the standard-treatment arm. Event-free survival was 77 percent in the arsenic trioxide arm vs. 59 percent in the control arm.

"Addition of two cycles of arsenic trioxide improved event-free and overall survival of people with APL," said study author Dr. Bayard L. Powell, a professor of hematology and oncology at Wake Forest University Baptist Medical Center in Winston-Salem, N.C. "There was very little additional toxicity, relapses were very uncommon. This should be incorporated into the therapy of patients with untreated APL."

A small study of 60 people found that the experimental drug axitinib shrank tumors in 22 percent of people with advanced thyroid cancer that was no longer responding to other treatments. Another 50 percent of patients saw their tumors stop growing altogether.

Axitinib, another anti-angiogenesis drug, inhibits receptors of vascular endothelial growth factor (VEGF), which promotes the growth of blood vessels. The trial, which is ongoing, is being funded by drug maker Pfizer Inc.

Finally, an interim analysis of the targeted therapy VEGF-Trap showed an effect in women with advanced ovarian cancer that is resistant to platinum-based chemotherapy agents.

Like Avastin, VEGF-Trap is an anti-angiogenesis drug and is being tested against several different cancers.

Tumors shrank in 8 percent of patients and stopped growing in 71 percent. This trial is also ongoing.

"VEGF-Trap blocks blood vessel development and tumor growth in a patient population which has few options," said study author Dr. William P. Tew, an assistant attending physician in the department of medicine at Memorial Sloan-Kettering Cancer Center in New York City. "It has an acceptable safety profile. We are continuing to accrue patients."

SOURCES: Len Lichtenfeld, M.D., deputy chief medical officer, American Cancer Society, Atlanta; Robert F. Ozols, M.D., Ph.D., senior vice president, medical science division, Fox Chase Cancer Center, Philadelphia; June 2, 2007, news conference with Bayard L. Powell, M.D., professor, hematology and oncology, Wake Forest University Baptist Medical Center, Winston-Salem, N.C., William P. Tew, M.D., assistant attending physician, department of medicine, Memorial Sloan-Kettering Cancer Center, New York City

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