Imatinib Performs Well in Patients after 5 Years

There was some good news last week for patients with chronic myeloid leukemia (CML), said Dr. Brian Druker of Oregon Health & Science University Cancer Institute at the ASCO annual meeting.

The first piece of good news is that imatinib (Gleevec) is "performing extremely well" in patients who have taken the drug for 5 years or longer, according to Dr. Druker, who led the development of imatinib for CML. The first study to assess the drug's benefit after 5 years found that nearly 90 percent of patients who received imatinib as their initial therapy were still alive. The survival rate was 95 percent when only CML-related deaths were included.

The drug was well tolerated over the long term: Only 5 percent of patients stopped taking it because of side effects. And after about the third year of taking the drug, the risk of relapse appears to begin to decrease. Moreover, the better a patient's response to the drug, the less likely it is that the patient will progress to advanced disease.

The second piece of good news is that "another drug is coming along" for patients who cannot tolerate imatinib, Dr. Druker noted. On Friday, the FDA's Oncologic Drugs Advisory Committee recommended accelerated approval of dasatinib for treating CML that resists prior therapy, including imatinib.

Combination trials will be undertaken, said Dr. Druker, who is planning a head-to-head trial comparing the drugs as first-line treatments. The question of which one to use will come down to response rate and tolerability, he said. Citing imatinib's impressive record over the long term, Dr. Druker has decided to use it as the first-line therapy for now. "But if dasatinib turns out to be better," he added, "I will go with it."

Adjuvant Gemcitabine Extends Survival for Pancreatic Cancer

Even if a patient's pancreatic cancer can be removed surgically, surgery alone rarely provides a cure. New results from a large randomized trial presented at the ASCO annual meeting suggest that the addition of the drug gemcitabine to adjuvant chemoradiation therapy using 5-fluorouracil (5-FU) for patients with pancreatic adenocarcinoma can significantly extend survival compared with adjuvant chemoradiation therapy using 5-FU alone.

In the RTOG 9704 trial, investigators randomly assigned patients to one of two groups: surgery, followed by gemcitabine given both before and after chemoradiation (experimental arm); or surgery, followed by 5-FU given both before and after chemoradiation (control arm).

Patients with tumors in the pancreatic head (the most common location) and patients with tumors in the pancreatic body or tail were included in the trial. Because of potential differences in the biology of tumors located in the body or tail of the pancreas, investigators increased the number of patients to be enrolled in the trial in order to have enough data to analyze patients with pancreatic head cancer as a subgroup.

More than 400 eligible patients participated in the trial. The addition of gemcitabine-based therapy significantly extended survival for patients with pancreatic head tumors: Those who received gemcitabine had a median survival of 20.6 months and 32-percent 3-year survival, compared with a median survival of 16.9 months and 21-percent 3-year survival in those who received only radiation therapy and 5-FU. But, when patients with pancreatic body or tail tumors were included in the analysis, the increase in survival was no longer significant.

"The addition of gemcitabine to postoperative adjuvant 5-FU chemoradiotherapy improves survival in patients with pancreatic head adenocarcinoma," stated Dr. William Regine, chief of radiation oncology at the University of Maryland Medical Center, Baltimore, who presented the results of the study, adding that future clinical trials can now build on this new treatment regimen to better improve survival for patients with this rare but deadly malignancy.

Breast Cancer Drug Anastrozole Increases Bone Loss

Women who take the drug anastrozole, an aromatase inhibitor, to prevent the recurrence of breast cancer should have their bone mineral density monitored and should take calcium and vitamin D supplements during therapy, researchers said at the ASCO annual meeting.

They made the recommendation based on a 5-year study showing that anastrozole was associated with a steady decline in bone mineral density. The bone loss was, on average, about 6-7 percent, or about twice the amount that would normally occur over that period.

However, no patients whose bone mineral density was normal at the start of the study developed osteoporosis after 5 years of treatment. To develop the condition, a woman would need to lose 15-20 percent of her normal bone mass.

The results are from the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial, which previously showed that anastrozole was superior to tamoxifen in preventing recurrences in women following surgery and radiation for early-stage breast cancer. Anastrozole is generally better tolerated than tamoxifen with fewer gynecological or thrombo-embolic complications, but is associated with more fractures and osteoporosis than tamoxifen, which preserves bone, according to the researchers.

"The overall risk-benefit ratio still favors taking anastrozole over tamoxifen," said Dr. Robert E. Coleman of the University of Sheffield, in the United Kingdom, who presented the findings at ASCO. But he said that women should have their bone mineral density measured at the start of treatment and then monitored every 1-2 years on therapy.

Treatments at End of Life Grew More Aggressive in 1990s

By the late 1990s, cancer patients were more likely to receive aggressive treatments near the end of their lives than patients who were treated at the start of the decade, researchers reported at the ASCO annual meeting. The findings, from an effort to identify quality measures for end-of-life care, confirm previous reports of a trend, for some physicians, toward intervening aggressively to treat patients very near death.

The trend includes an increase in the use of chemotherapy on patients within 2 weeks of death; an increase in multiple emergency room visits and admissions to intensive care units during the last month of life; and a greater proportion of patients admitted to hospice within 3 days of death.

Dr. Craig Earle of the Dana-Farber Cancer Institute and his colleagues analyzed statistics from NCI's Surveillance, Epidemiology, and End Results (SEER) database and Medicare billing records on 215,000 patients who died of cancer between 1991 and 2000.

Dr. Earle's team first described this trend several years ago. Although the aggressive treatments were not necessarily inappropriate, Dr. Earle says, they were often given to patients who had little or no chance of benefiting from them.

By developing quality measures for end-of-life care, the researchers intend to help physicians determine the most appropriate treatments for these patients. They also hope to raise awareness about issues related to end-of-life care.

Chemotherapy for NSCLC Benefits Elderly Patients

New data presented at the ASCO annual meeting on June 2 provided evidence that chemotherapy following surgery for elderly patients with non-small-cell lung cancer (NSCLC) improves survival, without an increase in treatment-related toxicity or hospitalization compared with younger patients.

Dr. Carmela Pepe of Princess Margaret Hospital in Toronto presented a retrospective analysis of the results from a clinical trial led by the National Cancer Institute of Canada in which patients with NSCLC had been randomly assigned following surgery either to chemotherapy with vinorelbine and cisplatin or to observation alone.

In the retrospective analysis, the investigators looked at whether the trial's previously reported overall survival advantage for the surgery plus chemotherapy group held even if the patients were elderly. They also examined whether there were differences between the elderly and younger patients in terms of the number of chemotherapy doses they received, the intensity of the doses, or the side effects.

Sixty-six percent of elderly patients who received chemotherapy were alive 5 years after treatment, compared with 46 percent in the surgery-alone group. This survival advantage was seen even though elderly patients received fewer - and less intense - doses than younger patients. Elderly patients who received chemotherapy were no more likely to experience toxic side effects or be hospitalized during treatment than were younger patients.

These results indicate that "Platinum-based chemotherapy can be given safely to elderly patients without significant risk of increased toxicity," said Dr. Pepe. "Therefore, adjuvant chemotherapy should not be withheld from elderly patients on the basis of age alone."