By Jennifer Klem, PhD

Taxotere Gives Time for Hormone-Refractory Prostate Cancer
Newly diagnosed prostate cancer is generally responsive to hormonal therapies, leading to responses that last up to two years. In virtually all men with metastatic prostate cancer, the tumor will eventually stop responding to hormonal agents, a condition called hormone-refractory prostate cancer (HRPC) that has an expected survival time of about one year.

The U.S. Food and Drug Administration (FDA) approved Taxotere^® (docetaxel) in combination with prednisone (a steroid) on May 19 for use in metastatic prostate cancer patients with HRPC. Taxotere is already approved for breast and lung cancers. The approval for prostate cancer was based on a global clinical trial in which patients received either treatment with the standard chemotherapy of Novantrone^® (mitoxantrone) and prednisone or Taxotere in combination with prednisone. Patients treated with Taxotere every three weeks had prolonged survival times compared to those treated with mitoxantrone chemotherapy, which was the only chemotherapy regimen approved by the FDA for HRPC. It was approved for its ability to improve quality of life, not to prolong survival time.

Taxotere, the first chemotherapy drug to demonstrate a survival advantage over mitoxantrone/prednisone in HRPC, gives men with metastatic HRPC another treatment option and the hope of living longer. To learn more about Taxotere, visit www.taxotere.com.

Oral Pill as Effective as Standard Chemotherapy
Xeloda^® (capecitabine) was recently found to be at least as effective as the standard I.V. chemotherapy regimen of 5-fluorouracil (5-FU) plus leucovorin (an agent that makes 5-FU more active) in a phase III clinical trial.

Patients in this trial received either oral Xeloda or 5-FU/leucovorin following surgery of their early-stage colon cancer. 5-FU has been used for decades in the fight against colon cancer but causes many side effects, including diarrhea‚ mouth irritation and lowered white blood cell counts. Xeloda, which converts to 5-FU within the body, has demonstrated more acceptable side effects than 5-FU. Since Xeloda has been shown to be as effective as 5-FU, patients may opt in the future for oral treatment of their colon cancer following surgery instead of traditional intravenous chemotherapy.

For more information, go to www.xeloda.com.

Tarceva Prolongs Life for Lung Cancer Patients
Results of a phase III trial of Tarceva™ (erlotinib) to treat patients with relapsed non—small-cell lung cancer (NSCLC) showed patients taking Tarceva lived, on average, two months longer than those taking a placebo. In addition, patients receiving Tarceva had greater tumor shrinkage and fewer symptoms with a 42.5 percent improvement in median survival and a 41 percent improvement in one-year survival rates compared to placebo.

Tarceva belongs to a class of drugs called tyrosine kinase inhibitors (like Iressa™ [gefitinib] and Gleevec^® [imatinib]) that more specifically affect certain signaling molecules on cancer cells. These drugs tend to have fewer side effects than standard chemotherapy.

Half of the lung cancer patients on this trial who had advanced relapsed NSCLC following one or two prior chemotherapy regimens received Tarceva, a pill that is taken daily. The other half received placebo. NSCLC, the most common form of lung cancer, accounts for almost 80 percent of all lung cancers.

As a result of this study, the U.S. Food and Drug Administration has granted Tarceva fast-track designation, designed to facilitate the review of drugs that show promise in meeting unmet medical needs. If approved, Tarceva could be available to patients with relapsed lung cancer in early 2005. The most common side effects of Tarceva noted in this trial and others are mild to moderate diarrhea and rash.

For more information on Tarceva, go to www.osip.com.

Another Piece in the Iressa Puzzle
Iressa™ (gefitinib) is an oral drug that was approved by the U.S. Food and Drug Administration (FDA) in May 2003 for use in relapsed non—small-cell lung cancer, the most common form of lung cancer. The drug’s approval, submitted under the FDA’s accelerated approval program, was based on a relatively small study of 216 patients with advanced disease, in which about 10 percent of the patients’ tumors shrank by at least 50 percent.

Some of these patients, however, experienced dramatic improvements, with some tumors completely disappearing. Further, responses to Iressa lasted a median of seven months, an encouraging number for patients whose expected survival is usually less than one year. The Oncologic Drugs Advisory Committee (ODAC) decided that these data, coupled with the knowledge that lung cancer patients who fail multiple chemotherapy regimens have no other treatment options, provided enough reasons to recommend Iressa’s approval.

Given that only 10 percent of patients benefit from Iressa, trying to determine which patients will be among the lucky ones has become an important issue.

Two independent studies recently published in The New England Journal of Medicine and Science suggest the mystery has been partially solved. Both groups found that mutations in a specific region of the epidermal growth factor receptor (EGFR), the molecule that is targeted by Iressa, produce tumors that are exquisitely sensitive to treatment with Iressa.

The studies found that these EGFR mutations occur more frequently in women and in patients with a type of tumor called adenocarcinoma, which would help explain why more women with lung cancer and patients with adenocarcinoma respond to this drug. Nevertheless, this information could lead to a screening test that identifies those patients who are likely to benefit from treatment with Iressa, possibly allowing earlier access to this drug for such patients.

For more information on Iressa, visit www.iressa.com.

Switching Hormonal Therapy May Benefit Breast Cancer Patients
Women whose breast cancers are positive for hormone receptors often receive hormonal therapy following surgery and radiation. For postmenopausal women, taking Nolvadex^® (tamoxifen) every day for five years is standard therapy. But tamoxifen can sometimes lead to complications, including an increased risk of endometrial cancer and blood clots.

As reported in the Winter 2003 issue of CURE, women who took a different hormonal agent called Femara^® (letrozole) after taking tamoxifen for five years had a decreased risk of breast cancer recurrence compared to women who took only tamoxifen for five years. These results provide women on tamoxifen therapy with an option to further reduce their risk of recurrence.

A study published in the March 11 issue of The New England Journal of Medicine found that patients benefited from switching from tamoxifen to yet another hormonal therapy agent called Aromasin^® (exemestane). This study differed from the Femara trial in that the women who switched therapies did so after two to three years instead of five years. In this study, 4,742 postmenopausal patients received either tamoxifen for five years or switched from tamoxifen to Aromasin after two to three years for a total of five years of therapy. Almost 5 percent more women receiving Aromasin were disease-free after three years than those receiving only tamoxifen. Patients who switched to Aromasin also had a lower risk of developing breast cancer in the other breast. As an added benefit, patients receiving Aromasin had fewer blood clots, although they did have a tendency to have more bone fractures than those patients who took only tamoxifen. (Tamoxifen is known to have a protective effect on the bones.) For details on Aromasin, go to www.aromasin.com and for more on tamoxifen, go to www.nolvadex.com.

New Option in the Fight Against Metastatic Breast Cancer
The U.S. Food and Drug Administration (FDA) approved the combination of Gemzar^® (gemcitabine) and Taxol^® (paclitaxel) for use in women with newly diagnosed metastatic breast cancer. The approval, which came May 19, was based on results of a phase III trial comparing Gemzar/Taxol to Taxol alone. Patients receiving the combination regimen demonstrated improved outcomes. Taxol is approved as a single agent for metastatic breast cancer and produces tumor shrinkage in up to 55 percent of patients. Gemzar is approved for lung cancer and pancreatic cancer.

In the study that led to the approval of Gemzar/Taxol, patients who were treated with the Gemzar/Taxol combination regimen experienced significantly longer time to progression than did those treated with Taxol alone. More of the patients receiving Gemzar/Taxol also had tumor shrinkage.

The FDA has approved the Gemzar/Taxol combination for use in patients with metastatic breast cancer who did not respond to or cannot take anthracyclines (like Adriamycin^® [doxorubicin] or Ellence^® [epirubicin]). The Gemzar/Taxol regimen can now be added to the arsenal of weapons in the battle against metastatic breast cancer.

For more information about Gemzar, go to www.gemzar.com.