+ + data and comments + +, page-15

re: + + drug pi-88 and its peers+ + I referred to "IRESSA" and the deaths in Japan.

Here is an older article. It does show that Iressa doesn't do wonders:
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WILMINGTON, Del. -- AstraZeneca Pharmaceuticals announced on May 5 that the U.S. Food and Drug Administration (FDA) had granted approval for Iressa (gefitinib) for the treatment of advanced non-small-cell lung cancer (NSCLC).

Iressa is approved only for life-threatening conditions – In this case, where no approved treatment existed.

The first of a new class of anti-cancer drugs, Iressa won majority backing from an FDA expert panel last September but final approval in the world's largest market was delayed while regulators examined additional clinical data.

AstraZeneca began shipping Iressa to pharmacies in mid-May, at a retail price of about $1,900 a month.

Iressa is administered as a once-a-day 250 mg. pill. It works differently than cytotoxic chemotherapy drugs commonly used for lung cancer.

Iressa is for patients with advanced lung cancer who have exhausted standard treatment. Iressa shrinks tumors in only a fraction of those terminally ill patients.

It's a controversial drug. Already sold in Japan, the health ministry there has linked it to 173 deaths from interstitial lung disease (ILD). Few users appear to get ILD, but it is fatal about a third of the time.

The U.S. Food and Drug Administration said it had enough evidence that Iressa offered some hope for patients already dying of their cancer to approve its U.S. sale even as Iressa's overall effectiveness continues to be studied.

One study of 216 advanced patients found 10 percent had their tumors shrink for at least a month while taking Iressa. Nobody yet knows if that translates into longer survival. But the shrinkage seems to last at least seven months, said FDA oncology chief Dr. Richard Pazdur.

Particularly intriguing is that Iressa seems to work significantly better for women – about 17 percent of them see tumor shrinkage vs. five percent of men. Also, it seems to work better for people who never smoked, a conundrum because smoking is the main, though not sole, cause of lung cancer. About one in six lung cancer victims has never smoked.

Another mystery centers on the fact that Iressa had no effect when more than 2,000 patients with early-stage cancer took it together with regular chemotherapy in two more stringent studies. No one knows why, although some scientists think combining regular chemotherapy with Iressa – which works by jamming one of a tumor's internal growth signals – could blunt the new drug's action.

The FDA warns that Iressa is not for use with other chemotherapies during early lung cancer treatment, and is requiring AstraZeneca to conduct more research to settle the issue.

Of about 28,000 Iressa users in Japan, about two percent developed ILD. In a U.S. study, less than half of one percent of some 23,000 people given Iressa in a special experimental program got ILD. In studies that compared Iressa to a placebo in people getting chemotherapy for early lung cancer, both groups came down with ILD equally – about one percent, the FDA said.

It can be hard to diagnose ILD in lung cancer patients, and other cancer treatments can cause ILD too, said FDA drug chief Dr. Robert Temple. Even if it turns out that one percent of Iressa users gets ILD, that's not a big enough risk to outweigh the drug's potential benefit to terminally ill patients, he said.

Iressa is indicated as a monotherapy for the treatment of patients with locally advanced or metastatic NSCLC after failure of both platinum-based and docetaxel chemotherapies. The effectiveness of IRESSA is based on objective response rates. There are no controlled trials demonstrating a clinical benefit, such as improvement in disease-related symptoms or increased survival. Results from two large, controlled, randomized trials in first-line treatment of NSCLC (INTACT I & II) showed no benefit from adding Iressa to a doublet, platinum based chemotherapy. Therefore, IRESSA is not indicated for use in this setting. As part of this accelerated approval, AstraZeneca will be completing Phase IV clinical studies, which are designed to satisfy FDA requirements for full approval.

The most frequent drug-related adverse events associated with IRESSA were diarrhea (48 percent) sometimes associated with dehydration, rash (43 percent), acne (25 percent), dry skin (13 percent), nausea (13 percent), and vomiting (12 percent). These events generally occurred within the first month of therapy and usually were mild to moderate.

The reported incidences of ILD in the 23,000 patient US expanded access program was about 0.3 percent. In Japanese post-marketing experience the reported rate of ILD was about two percent. In the phase III controlled studies in combination with chemotherapy, there were similar rates of ILD (about one percent) reported in both the placebo and Iressa arms of the study.