Science + Technology

Successful New Breast Cancer Treatment Announced by Revlon/UCLA Women's Cancer Research Program

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Researchers at UCLA's Jonsson Comprehensive Cancer Center today (May17) announced a significant medical breakthrough: positive results of extensivetrials of a new breast cancer drug that is the first successful cancertreatment targeted to attack a specific genetic alteration. The treatmentis not yet available to the general public.

UCLA's cancer center developed the drug with financial support fromthe Revlon/UCLA Women's Cancer Research Program and in conjunction withthe pharmaceutical company Genentech Inc. of South San Francisco.

The drug, called Herceptin, can be effective for breast cancer patientswho have an overabundance in their tumor cells of a gene called HER-2/neu.About 30 percent of women with breast cancer fall into that category.

"Herceptin is the first successful cancer treatment that targetsa specific genetic alteration as opposed to using a shotgun approach thatkills both diseased and healthy cells," said Dr. Dennis Slamon ofUCLA's Jonsson Cancer Center, director of the Revlon/UCLA Women's CancerResearch Program and lead scientist in the discovery research and earlydevelopment of Herceptin.

"And Herceptin has none of the serious side effects associatedwith traditional chemotherapy, such as nausea, vomiting, hair loss or significantdrops in blood counts," Slamon continued. "A few patients usingHerceptin who have used or are using the drug Adriamycin experience cardiacabnormality, but in most cases the situation can be remedied and patientscan continue using Herceptin."

Experimental Herceptin treatments were given to women for whom the bestavailable standard chemotherapy was judged to be either a combination ofthe drugs Adriamycin and Cytoxin or the single drug Taxol.

When taken in combination with the drugs Adriamycin and Cytoxin, Herceptinresulted in a significant response (a 50 percent or greater measurablebreast cancer reduction) in 52 percent of patients, as opposed to similarresults in just 43 percent of patients who took Adriamycin and Cytoxinalone. So using Herceptin in combination with Adriamycin and Cytoxin was20 percent more effective than using Adriamycin and Cytoxin alone.

Results were even more impressive among women who took Herceptin incombination with the drug Taxol. While significant response to Taxol alonewas only 16 percent, women taking Taxol in combination with Herceptin hadsignificant responses in 42 percent of the cases, representing a 160 percentimprovement.

Overall, the Herceptin/chemotherapy combinations caused a significantdecrease in measurable breast cancer in 48 percent of patients, whereasonly 32 percent experienced significant response with chemotherapy alone.In other words, patients using Herceptin in combination with chemotherapyhad a 50 percent better response rate than patients using chemotherapyalone. Moreover, that better response rate was accompanied by a greaterthan 60 percent increase in duration of the response over what was foundin women treated with the chemotherapy alone.

(In a trial being reported separately, 22 percent of patients who tookHerceptin alone experienced a 50 percent or greater measurable reductionin breast cancer.)

Results of the Herceptin trials were announced in Los Angeles at theAmerican Association of Clinical Oncology after a 2 -year worldwidestudy.

Women entering the trial were "randomized" so that approximatelyhalf of them received Herceptin combined with the best available chemotherapyand the other half received chemotherapy alone.

"The success of Herceptin opens a new frontier in cancer treatment,"Slamon said. "Not only did it exceed our expectations as a drug againstbreast cancer, but because about 20 percent of women with ovarian canceroverexpress the HER-2/neu gene, we think it may also be effective for womenwith that disease."

Slamon emphasized that Herceptin does not work for all patients whooverexpress the HER-2/neu gene, and that the drug is not yet availableto the general public.

"We are working in the lab right now to find out why Herceptindoes not help all women who overexpress the HER-2/neu gene," Slamonsaid.

The HER-2/neu gene is involved in the replication of many types of cells.However, when the gene is present in extra numbers, and as a result isoverexpressed in breast or ovarian cancer cells, those cells replicateout of control, causing cancer.

Slamon said he and his colleagues are currently investigating the relationshipbetween the HER-2/neu gene and various other cancers.

HER-2/neu genes produce a specific protein in the cell. That proteinis found on the cell surface, where it acts like a tiny antenna, receivingsignals from outside of the cell and relaying those signals to the nucleusto tell the cell to split, or replicate.

In a cell that overproduces the HER-2/neu protein, Herceptin binds tothe protein "antenna," preventing the cell from receiving and/ortransmitting the growth stimulatory signal that would tell it to replicate.

"The next step is to seek the most expeditious FDA approval routefor Herceptin, based on the data in our trials," Slamon said. "We'rehoping for that approval before the end of this year."

-UCLA-

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