By Jennifer Klem, PhD, Susan Peck, PhD, & Nancy Price, PhD

Second Look at Chemotherapy After Lung Cancer Surgery

Surgery offers the best chance for a cure in early-stage non—small-cell lung cancer (NSCLC). Using chemotherapy after surgery to eliminate the undetectable metastases that remain following surgery has had disappointing results in clinical trials with patients receiving no additional benefit from chemotherapy following surgery.

But two recent phase III clinical trials reported at the 2004 meeting of the American Society of Clinical Oncology found that chemotherapy administered immediately after surgery increased patient survival. In one trial, patients with early-stage NSCLC received either 1) a chemotherapy regimen after surgery or 2) no treatment following surgical removal of their tumor. A comparison of the two groups showed that patients receiving chemotherapy had a median survival time of 7.8 years—21 months longer than the group without chemotherapy.

The second trial, which was very similar, was stopped early when it was clear the survival of patients who received chemotherapy was much better than for those with no chemotherapy. Eleven percent fewer patients receiving chemotherapy either died or suffered a relapse compared to the group without chemotherapy. The reason for the newly reported benefit in chemotherapy following surgery for lung cancer patients is not entirely clear, although several factors are possible, including better trial designs and improved chemotherapy regimens.

Taken together, the results of these two most recent trials suggest that chemotherapy following surgery can prolong survival in early-stage lung cancer patients. For more on lung cancer, visit www.alcase.org.

Alimta Approved for Relapsed Lung Cancer Patients

Alimta® (pemetrexed) has become the second drug approved for patients with relapsed, advanced non—small-cell lung cancer (NSCLC) following Taxotere® (docetaxel).

Alimta was approved earlier this year for use in patients with malignant pleural mesothelioma, a relatively rare but aggressive cancer often linked with asbestos exposure. Recently, results from a large phase III trial comparing Alimta to Taxotere in relapsed NSCLC patients with advanced disease were reported in the Journal of Clinical Oncology. In this direct comparison, the investigators reported that patients receiving Alimta fared just about as well as those who received Taxotere.

The numbers were similar when comparing tumor shrinkage in response to treatment (9.1 percent for Alimta and 8.8 percent for Taxotere). And the same was true for the median survival time (8.3 months for Alimta and 7.9 months for Taxotere). In addition, Alimta produced fewer side effects, including fewer incidences of neutropenia with fever, fewer hospitalizations due to neutropenic fever or other treatment-related problems, fewer infections and less hair loss.

In August 2004, the Food and Drug Administration granted accelerated approval for Alimta in the second-line treatment of advanced or metastatic NSCLC. To learn more about Alimta, visit www.alimta.com.

Improving the Mix for Presurgical Chemotherapy

Herceptin® (trastuzumab), an antibody that targets HER2, has produced dramatic results in metastatic breast cancer. When added to chemotherapy regimens for women with HER2-positive metastatic breast cancer, Herceptin increases the time to disease progression, improves response rates and extends overall survival.

For women with early-stage breast cancer, chemotherapy prior to surgery is often used to shrink the tumor, improving surgical outcomes. Herceptin is now being studied in combination with chemotherapy in women with operable HER2-positive breast cancer. A recent study showed that the addition of Herceptin to chemotherapy dramatically improved response rates. Complete response rates increased to 65 percent with Herceptin as compared to 26 percent in patients treated with chemotherapy alone.

Although the number of patients involved in this study was small (42), the results suggest that for women with HER2-positive breast cancer who are planning to receive presurgical chemotherapy to shrink their tumors, adding Herceptin to the regimen may lead to a more beneficial outcome. For more information, go to www.herceptin.com.

New Ammunition Against Early-Stage Breast Cancer

More than 300,000 women worldwide will be diagnosed with early-stage breast cancer that has spread to the lymph nodes. On Aug. 18, the FDA gave these women another postsurgical therapy choice by approving Taxotere® (docetaxel) in combination with Adriamycin® (doxorubicin) and Cytoxan® (cyclophosphamide).

The FDA based its approval on a trial of almost 1,500 women that compared the use of Adriamycin and Cytoxan with either Taxotere (TAC) or 5-FU (FAC). Results showed that women receiving TAC following surgery had a 26 percent reduction in their risk of recurrence. Patients taking TAC also experienced prolonged survival when compared to women receiving FAC. Although TAC caused more side effects, the percentage of people completing all six cycles of therapy was similar for both regimens (over 90 percent). For more information on Taxotere, visit www.taxotere.com.

Finding the Key to Overcoming Gleevec Resistance

Chronic myelogenous leukemia (CML), a slow-growing but life-threatening disorder of the white blood cells, is caused by a genetic mutation that results in production of an abnormal protein called BCR-ABL (see CURE, Fall 2002). Gleevec® (imatinib) blocks the activity of ABL protein and represents a breakthrough in the treatment of CML by producing dramatic remissions with few side effects.

But over time, approximately 10 percent of patients taking Gleevec become resistant. Fortunately, there may be a new option for these patients. In a study published in the July 16 issue of Science, a team of researchers from UCLA reported that a new oral compound, BMS-354825, can block both the activity of Gleevec-resistant CML cells (14 out of 15 tested) and their growth-promoting activity. Early clinical trials are showing promise in patients with chronic-phase CML.

Another drug with potential activity against Gleevec-refractory CML, AMN107, is being developed by Novartis for application in more advanced CML patients (accelerated phase or blast crisis). For more information on CML, go to www.lls.org.