• Explain to patients that treatment with a drug that promotes bone health improved overall survival in men with metastatic prostate cancer to bone.
• The drug did not improve survival in men with locally advanced prostate cancer without metastases.

Men with advanced prostate cancer lived significantly longer when treated with sodium clodronate, but the adjuvant therapy had no effect on survival in men with nonmetastatic disease, British investigators reported.

The oral bisphosphonate reduced the mortality hazard by 23% in men with advanced prostate cancer, Matthew R. Sydes, of the Medical Research Council (MRC) in London, and colleagues reported in the Aug. 11 issue of The Lancet Oncology.

But men with nonmetastatic prostate cancer had essentially the same mortality when treated with clodronate or placebo.

“[This] is the first trial, to our knowledge, to show an overall survival benefit conferred by an oral bisphosphonate when given in addition to standard hormone therapy to men with bone metastases who are starting or responding to hormone therapy for prostate cancer,” the authors concluded.

The findings essentially confirmed the primary outcomes of two randomized, placebo-controlled clinical trials begun 15 years ago to determine whether bisphosphonates modulate development or progression of bone metastases in men with prostate cancer when added to standard therapy.

One trial involved 311 men with bone metastases, while the other included 508 men with nonmetastatic disease.

Patients received oral clodronate for three years in the metastatic trial and for five years in the nonmetastatic trial. The primary results showed a nonsignificant trend toward improved survival in men with bone metastases and no evidence of a benefit from clodronate in nonmetastatic disease (J Natl Cancer Inst 2003; 95: 1300-11; J Natl Cancer Inst 2007; 99: 765-76).

The current report encompassed data on long-term survival. The analysis showed that 93% of men in the metastatic trial died during a median follow-up of 11.5 years, as did 60% of men followed for a median of 12 years in the nonmetastatic trial.

In the metastatic trial, men treated with clodronate had an overall survival hazard ratio of 0.77 compared with the placebo group (95% CI 0.60 to 0.98, P=0.032). Primary results of the trial showed a hazard ratio of 0.80 in favor of clodronate, which was not significantly different from placebo at that point.

Consistent with the primary results, long-term follow-up data showed no survival benefit with clodronate in the nonmetastatic trial (HR 1.02, 95% CI 0.89 to 1.42).

Primary source: The Lancet Oncology

Source reference:

Dearnaley DP, et al “Adjuvant therapy with oral sodium clodronate in locally advanced and metastatic prostate cancer: Long-term overall survival results from the MRC PR04 and PR05 randomized controlled trials” Lancet Oncol 2009; DOI:10.1016/S1470-2045(09)70201-3.

Earn CME/CE credit
for reading medical news

Childhood diabetes, according to a report in the August 10/24 issue of Archives of Internal Medicine, one of the JAMA/Archives journals. This correlation does not appear to be related to patients’ body mass index or physical inactivity.

“As a result of their curative therapies, childhood cancer survivors face an increased risk of morbidity and mortality,” with almost 75 percent of survivors developing a chronic health condition and 42.4 percent developing a severe, disabling or life-threatening condition 30 years after diagnosis, according to background information in the article. Cardiovascular disease, in particular, is a significant cause of deaths in this group. “In the general population, diabetes mellitus is strongly associated with an increased risk of cardiovascular disease and all-cause death.”

Lillian R. Meacham, M.D., of Emory University and AFLAC Cancer Center and Blood Disorders Service, Atlanta, and colleagues compared the prevalence of diabetes in a sample of 8,599 childhood cancer survivors (diagnosed before age 21 between 1970 and 1986) and 2,936 randomly selected siblings of the survivors (average ages 31.5 and 33.4 at follow-up in 2003, respectively). Medication use, treatment exposures (including irradiation, or exposure to radiation treatments) and factors that may have modified the risk of diabetes were noted.

Of the survivors, 218 (2.5 percent) reported having diabetes, while 49 (1.7 percent) of siblings reported having the condition. “After adjustment for body mass index, age, sex, race/ethnicity, household income and insurance, the survivors were 1.8 times more likely than the siblings to report diabetes mellitus, with survivors who received total body irradiation, abdominal irradiation and cranial irradiation at increased risk,” the authors write. “Survivors who were treated with abdominal irradiation were 2.7 times as likely to report diabetes mellitus as those who were not treated with abdominal irradiation or total body irradiation; those treated with total body irradiation were 7.2 times as likely to report diabetes mellitus.”

Survivors diagnosed with cancer before age 5 were 2.4 times more likely to report diabetes than those diagnosed in late adolescence (from ages 15 to 20). “As in the general population, older age, black or Hispanic/Latino background, lower household income, physical inactivity and increased BMI were associated with an increased risk of diabetes mellitus,” they note.

“It is likely that this additional chronic disease in childhood cancer survivors, who frequently also sustain damage to the heart, kidneys and endocrine system, will lead to further morbidity and premature mortality,” the authors conclude. “Therefore, it is imperative that clinicians recognize this risk, screen for diabetes and prediabetes when appropriate and approach survivors with aggressive risk-reducing strategies. Moreover, further research is warranted to understand the pathways by which these two modes of radiation therapy lead to diabetes.”

Arch Intern Med.. 2009;169[15]:1381-1388.

Source
Archives of Internal Medicine

Strength-training exercises after breast cancer surgery won’t worsen lymphedema and may actually reduce its symptoms, a randomized trial showed.

Weight lifting had no effect on the risk of arm swelling in postop breast cancer patients who already had lymphedema (11% of patients versus 12% of controls had at least 5% volume increase), Kathryn H. Schmitz, PhD, MPH, of the University of Pennsylvania in Philadelphia, and colleagues found.

But lymphedema symptoms and incidence of exacerbations dropped significantly in patients who followed a slow, progressive routine of resistance training, the researchers reported in the Aug. 13 issue of the New England Journal of Medicine.

These findings challenge the traditional recommendations against heavy lifting and resistance-training exercises that “overtire an arm at risk,” noted Wendy Demark-Wahnefried, PhD, RD, in an accompanying editorial.

• Explain to interested patients that lymphedema occurs when lymph nodes are removed in the course of breast cancer treatment and the body can no longer efficiently remove fluid from the arm.
• Note that the study included only women with a history of lymphedema, which is considered treatable but incurable, so the results cannot be generalized to at-risk women who do not have lymphedema.

Those commonly used guidelines have actually been counterproductive, Schmitz said.

“By giving this advice, what might be happening is that those women’s arms are becoming weaker and weaker,” she explained in an interview.

“So when they do find themselves in a situation where they have to use the affected arm,” she said, “almost anything they do with the arm will cause strain and, potentially, injury to the arm and may cause worsening of lymphedema.”

Slowly building strength may allow the arm to withstand stress and strain without injury, she said.

But although the study results provide strong reassurance of safety for even a high-risk population, precautions still apply, cautioned Schmitz.

Compression stockings were used in the study during exercise, and women still need to be cautious about injuring their affected arm, she said. “Anything you can do to avoid things that are going to strain and stress the arm is a good idea.”

Nor do the results imply weight training prevents lymphedema, Schmitz said.

Her group’s trial included 141 breast cancer survivors with stable lymphedema randomized to usual care without a change in exercise level or to twice-weekly, whole-body resistance training with increasing weight and repetitions done initially in group classes then on their own.

After one year, as expected, women in the weight-lifting group had improved more in upper- and lower-body strength than those under usual care (both P<0.001).

However, worsening of lymphedema by at least 5% volume increase was no more common with weight training (cumulative incidence ratio 1.00, 95% confidence interval 0.88 to 1.13).

Women in the weight-lifting group also had greater improvements in self-reported severity of lymphedema symptoms compared with controls (between group difference in change from baseline -0.29 on a 4-point scale, P=0.03).

Flare-ups of lymphedema — assessed by a certified lymphedema specialist — were half as common with strength training as with usual care (9 [14%] versus 19 [29%], P=0.04), yet a nearly equal number of patients in the weight-training group sought consultation for a possible exacerbation (20 versus 23 in the control group).

Adjustment for cancer stage, number of nodes removed, race, and baseline physical activity, diet, and body mass index did little to change the results. Nor were there any serious adverse events related to the exercise intervention.

Cancer specialists asked about the implications of these results were generally positive but saw some challenges.

Ruth Oratz, MD, of NYU School of Medicine in New York City, was skeptical that the results would have much impact on practice since arm swelling — “the outcome women really care about” — was unchanged.

“Old dogma is hard to change,” agreed Christine Laronga, MD, of the Moffitt Cancer Center in Tampa, Fla.

However, this study finally provides data in an area that has been largely based on anecdote with little literature to go on, said Laronga.

Also, commented Kent C. Osborne, MD, of Baylor College of Medicine in Houston, lymphedema is no longer the common problem it once was — incidence plummeted with introduction of less radical surgery and sentinel lymph node biopsy.

But Schmitz countered that as breast cancer survival rates have climbed the ranks of at-risk and lymphedema-affected women have risen as well.

Where lymphedema still has its strongest hold is in disadvantaged populations, which tend to have a higher stage at diagnosis that requires more aggressive treatment, Demark-Wahnefried noted.

Strength-training intervention may be particularly worthwhile in these women because they also have more severe consequences for employment and fewer economic resources to cover loss of function, she wrote.

The researchers noted potential limitations of the study including the fact that the evaluations for exacerbations were not done by a single therapist and the possibility that some assessors may have become aware of the control/treatment assignments of the participants.