A new drug may clear the haze of chemo

[RandyW]

A new drug may clear the haze of chemo

Modafinil, used to treat narcolepsy, enhances concentration for cancer patients.

By Thomas H. Maugh II

June 11, 2007

Related

- American Society of Clinical Oncology

- Chemo brain: A blog

- Small cell lung cancer

By the time Brenda Oathout had finished chemotherapy for her breast cancer, the Caledonia, N.Y., woman noticed a distinct change in her ability to think.

"Everything was a struggle. I couldn't remember things," she said. "Forgetfulness is not a strong enough word. My thought process was clouded. The more you struggle to think and remember, the more fatigued you become. By 3 o'clock, I was exhausted, overwhelmed with life."

Oathout, a 56-year-old financial advisor, was suffering from a condition known as chemo brain, a side effect associated with many forms of cancer chemotherapy, but particularly with treatment for breast cancer.

Many oncologists do not believe it is a real condition, but three papers published last December provided a strong scientific foundation to the idea. They showed that chemotherapy drugs can kill brain cells and that the brains of women who are receiving them undergo significant changes.

Oathout's life changed when she was invited to enroll in a new clinical trial at New York's University of Rochester Medical Center studying the effects of modafinil, a drug already being used to treat the sleeping disorder called narcolepsy.

"The very first day I took it, I noticed the difference," she said. Now, "I can be me again — mother, grandmother, wife, good employee. All the things that I used to be that I had lost for a while."

Results of this trial were among several promising advances reported last week at a Chicago meeting of the American Society for Clinical Oncology.

Among the others: news of the first drug shown to increase survival in liver cancer, data showing that irradiation of the head can reduce spread of one type of lung cancer to the brain, and findings that many breast cancer patients can do well with fewer radiation treatments.

For Oathout, the benefits of modafinil were so great that she now pays $742.48 a month out of her own pocket for the drug because her insurance company will not.

Oathout was one of 68 breast cancer victims who enrolled in a study by Sadhna Kohli of Rochester's James P. Wilmot Cancer Center on the effects of modafinil, which is sold by Cephalon Inc. under the trade name Provigil. Although the study was small, it demonstrated great potential for using the drug to treat this disabling aftereffect of cancer therapy.

In Kohli's study, all the women received modafinil for four weeks, then half received it for another four weeks and half received a placebo. All were given standardized tests to assess their powers of concentration and memory.

After four weeks, the women had faster recall of things they had seen and could recognize words and pictures more accurately. At the end of eight weeks, among the women who continued to receive the drug, their attention deficits had improved and their memory was even better, Kohli said.

Sunita Patel, a neuropsychologist at City of Hope National Medical Center, said that even a small improvement in mental functioning can have a dramatic effect on how women getting chemo feel and how they perform on the functions of everyday life. Of the study, she said, "I'm a little cautious because there is so little data yet, but this is definitely good news."

The study was sponsored by Cephalon and the National Institutes of Health.

Scientists at the meeting also reported on a new therapy for liver cancer, a particularly pernicious disease that has defied most attempts to treat it. Since 1970, experts said, there have been more than 100 clinical trials of potential treatments for the disease with no successes.

Furthermore, the incidence of the disease is increasing dramatically because of the spread of hepatitis, which is one of the primary causes of liver cancer. In the United States, about 19,000 people contract liver cancer each year, with 17,000 dying. Those numbers have doubled over the last 20 years, primarily because of increases in hepatitis C.

Worldwide, liver cancer kills 622,000 people annually, making it the third leading cause of cancer deaths.

The new drug is called sorafenib, marketed under the brand name Nexavar by Onyx Pharmaceuticals Inc. of Emeryville and the German pharmaceutical company Bayer Corp. A new study reported at the Chicago oncology meeting shows that patients who receive it live 44% longer than those who do not.

Nexavar is truly "a breakthrough," said Dr. Yun Yen, head oncologist in the liver program at City of Hope. "It sets a new standard for liver cancer. From now on, all comparisons of new drugs will have to be made to Nexavar."

Already approved by the Food and Drug Administration for the treatment of kidney cancer, sorafenib has a two-fold mode of action: It blocks signals that cause the cancer cells to proliferate, and it prevents the formation of blood vessels that provide nutrients to the tumor.

Dr. Joseph Llovet, of the Mount Sinai School of Medicine in New York, and his colleagues enrolled 602 European patients, half of whom received the drug and half a placebo. Those receiving sorafenib had a median survival of 10.7 months, compared with 7.9 months for those receiving the placebo.

"This is the first time we have had an effective systemic treatment for liver cancer," Llovet said.

Side effects included diarrhea, skin reactions in the hands and feet, fatigue and bleeding.

The primary drawback of the drug is the cost: about $5,000 a month or $60,000 a year — well beyond the means of most patients worldwide who need it.

Two other drugs also show potential for use against liver cancer in studies at an earlier stage — Sutent, manufactured by Pfizer Inc.; and Avastin, manufactured by Genentech Inc. Both, already approved by the FDA for other uses, have mechanisms similar to that of Nexavar.

Pfizer and Genentech hope to have results from clinical trials by next year.

Another encouraging result reported at the meeting was for small-cell lung cancer, which accounts for about 15% of U.S. lung cancers, or about 32,000 a year. One of this cancer's disturbing aspects is a tendency to metastasize to the brain, where small tumors cause cognitive and physical difficulties.

A new Dutch study found that prophylactic irradiation of the head after chemotherapy can reduce brain metastases by two-thirds, extending patients' survival. "This should become the standard of care almost immediately," said University of Texas M.D. Anderson Cancer Center's Dr. Roy Herbst, who was not involved in the study.

In the study, Dr. Ben Slotman, of the VU University Medical Center in Amsterdam, and his colleagues treated 143 patients with advanced small-cell lung cancer whose tumors had shrunk with chemotherapy. The patients received daily doses of radiation for one to two weeks at doses normally used to treat brain metastases. A control group of 143 similar patients received no radiation.

A year later, Slotman reported, only 14.6% of the radiation group had brain metastases, compared with 40.4% of the control group. And 27.1% of the patients in the radiation group were still alive, compared with 13.3% of control patients.

The treatment was associated with mild side effects that included nausea, vomiting and mild headache.

"Because improvements in treatment results for patients with advanced small-cell lung cancer have been minimal in the past two decades, these findings represent a major advance," Slotman said.

Meanwhile, Scottish researchers reported at the meeting that breast cancer patients may be receiving more radiation treatments than they need to forestall recurrence of their disease. Typically, women get daily doses of radiation for five weeks, totaling about 50 Grays, the standard unit for radiation.

Dr. John Dewar of the University of Dundee led a study of 4,500 women in the United Kingdom examining whether less frequent doses would be equally effective. Less frequent treatment would be especially valuable for women who live far from their medical centers or who have difficulties getting there regularly.

One-third of the women received the normal course of 50 Grays in 25 treatments, a third received 41.6 Grays given in 13 treatments every other day for five weeks, and a third received 40 Grays given in 15 doses over three weeks.

After five to six years, the recurrence rates ranged from 2.2% to 5.9%, with the smallest rate in the group receiving 40 Grays.

"These findings suggest that women can safely undergo a less demanding course of radiation therapy without appearing to increase their risk of recurrence," Dewar said.

He cautioned, however, that the recurrence rates were so small in all groups that longer term follow-up may be necessary to assess the efficacy of the new treatments.

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