Arsenic Trioxide Improves Survival in Adults with APL

Recent results from a Cancer and Leukemia Group B (CALGB) phase III clinical trial showed that adult patients with acute promyelocytic leukemia (APL) who received arsenic trioxide (Trisenox) in addition to standard chemotherapy had significantly better event-free and overall survival than those who received only standard chemotherapy.

The NCI-sponsored CALGB study tested the effects of arsenic trioxide on 582 patients between June 1999 and March 2005. Patients with newly diagnosed APL, an uncommon form of leukemia, were randomly assigned to one of two treatment groups. The standard remission treatment group received the chemotherapy drugs daunorubicin and cytarabine with twice daily doses of all-trans retinoic acid (ATRA) followed by the standard postremission regimen of two more courses of ATRA plus daunorubicin. The experimental treatment group received the same standard treatment with the addition of two courses of arsenic trioxide given immediately after the patient entered a complete or partial remission and before the standard postremission regimen.

The researchers found that 77 percent of those adult patients in the combined chemotherapy and arsenic trioxide treatment group remained in remission 3 years after diagnosis compared to 59 percent of patients receiving only the standard treatment. In addition, 86 percent of adult patients on the combined chemotherapy and arsenic trioxide treatment regimen were still alive after 3 years compared to 77 percent of patients on the standard treatment.

Study co-investigator Dr. Richard Larson from the University of Chicago noted, "These results indicate that arsenic trioxide should be considered as part of the initial treatment of patients with acute promyelocytic leukemia."

Radiation After BCS Benefits Older Women with Breast Cancer

A study from the NCI-sponsored Cancer Research Network published online in Cancer on January 22 has shown that women aged 65 or older who receive radiation therapy after breast-conserving surgery (BCS) and 5 years of tamoxifen therapy have a reduced risk of cancer recurrence compared with those who do not receive these standard treatments.

Investigators led by Dr. Ann M. Geiger of Wake Forest University searched the medical records at six HMOs in the Cancer Research Network for women aged 65 or older who underwent surgery for early-stage breast cancer between 1990 and 1994. They recorded whether women had a full mastectomy, BCS followed by radiation therapy, or BCS alone. They also recorded the incidence and duration of tamoxifen use in women with hormone-receptor-positive tumors.

After adjusting for known prognostic variables, the investigators found that women who underwent BCS without radiation therapy had an increased risk of recurrence or second primary breast cancer compared with women who had a full mastectomy. In contrast, women who received radiation therapy in addition to BCS did not have an increased risk of either recurrence or a second primary cancer. Women with hormone-receptor-positive tumors who received 5 or more years of tamoxifen therapy were less likely to have a recurrence or second primary cancer than women who received tamoxifen for less than a year.

Radiation therapy following BCS and tamoxifen benefited women regardless of age, race, ethnicity, or comorbidities. Because several recent studies have shown that older women are less likely to receive standard cancer therapies, the authors stress "the importance of providing high-quality cancer care to all patients, regardless of age."

Study Confirms Cigarettes Packing More Nicotine Punch

Cigarette smoke-nicotine yields increased 11 percent between 1998 and 2005. That is the conclusion of a new report from the NCI-supported study by the Tobacco Research Program at the Harvard School of Public Health (HSPH), which analyzed data from the nation's major tobacco manufacturers.

The new report echoes findings from a similar report released last summer by the Massachusetts Department of Public Health. Massachusetts law requires all manufacturers of cigarettes sold in the state to provide a comprehensive annual report on nicotine yield and other measures of cigarettes design. Smoke-nicotine yields are measured using a standardized machine-generated method that compares cigarettes, regardless of individual smoking behavior.

The researchers identified two ways the cigarette manufacturers appear to have increased the smoke-nicotine yield: a higher concentration of nicotine in the tobacco rod (the portion of the cigarette that holds the majority of the tobacco) and a reduced "burn rate," which permits more puffs per cigarette. The researchers cautioned that these two factors could not account for the total increase seen and that "precise information about these products remains shrouded in secrecy, hidden from the public."

"Our findings call into serious question whether the tobacco industry has changed at all in its pursuit of addicting smokers since signing the Master Settlement Agreement of 1998 with the State Attorneys General. Our analysis shows that the companies have been subtly increasing the drug nicotine year by year in their cigarettes, without any warning to consumers since the settlement," said the study's lead author, Dr. Gregory Connolly, a professor of the practice of public health at HSPH.

The study authors note that "all cigarettes are highly addictive and deadly, and relatively minor changes in nicotine yield may not significantly alter the product's addictive properties." They suggest that the increased nicotine may be intended to make it easier for smokers to maintain their addiction, including lower income smokers who may be smoking fewer cigarettes as the price of tobacco products increases.

Women May Be Quitting Tamoxifen More Often than Thought

When women who have early-stage, hormone-responsive breast cancer take adjuvant tamoxifen for 5 years, it can dramatically reduce their risk of breast cancer recurrence and death. But sometimes women stop the treatment early and forgo these benefits. A study published online January 22 in Cancer reveals that the number of women who do this may be higher than previously thought.

Researchers at St. James's Hospital in Dublin analyzed records from a national database that logs prescriptions filled through the Irish government's free health care system, which serves approximately one-third of the country's population. The final study cohort included 2,816 women over the age of 35 who had filled tamoxifen prescriptions between January 2001 and January 2004.

Previous studies have estimated the rate of nonpersistence, or discontinuing treatment with tamoxifen, at between 16 and 32 percent within 5 years. The current study, which is the largest thus far, showed that the discontinuation rate was 35.2 percent after a follow-up of just 3.5 years. "It is likely that persistence with tamoxifen will have declined further by the time the cohort of patients in this study has completed 5 years of treatment," the authors warn. Some factors associated with nonpersistence included younger age (under 44) and older age (over 75).

The authors speculate that younger women may have difficulty accepting a diagnosis of breast cancer and thus may be less accepting of tamoxifen's side effects. They also note that because some types of antidepressants have been shown to decrease severe hot flashes, these drugs may improve persistence by minimizing side effects.

SWOG Closes Prostate Cancer Trial

The NCI-sponsored Southwest Oncology Group (SWOG) last week announced that it has closed a phase III prostate cancer treatment clinical trial because the new treatment under investigation was associated with a rare but dangerous side effect.

The trial, dubbed S9921, was designed to see whether hormone-deprivation therapy combined with the chemotherapy drug mitoxantrone was superior to hormone-deprivation therapy alone in men with "poor risk" prostate cancer - that is, cancer that had spread beyond the prostate and was at high risk of recurring after surgery or radiation therapy.

Mitoxantrone has already been approved by the Food and Drug Administration for the treatment of advanced prostate cancer. Of the 983 patients enrolled in the trial, 488 had received mitoxantrone as part of their treatment. In the most recent review of survival and side-effect data from the trial, SWOG explained in a statement, trial leaders noted three cases of acute myelogenous leukemia among the patients who had received mitoxantrone. No patients in the hormone deprivation-only group developed leukemia.

Following a review and recommendation from SWOG's Data Safety Monitoring Committee, the trial was closed.