ADT for Prostate Cancer

In the 1990s, reversible androgen suppression with the use of luteinizing hormone–releasing hormone analogues and oral antiandrogen agents was shown to induce apoptotic regression in androgen-responsive cancers, potentially improving the prospects of local control and the duration of survival free of metastatic disease.
Clinical Pearls

How can short-term androgen deprivation be achieved?
In this study, patients assigned to short-term androgen-deprivation therapy (ADT) received flutamide at a dose of 250 mg orally three times a day and either monthly subcutaneous goserelin at a dose of 3.6 mg or intramuscular leuprolide at a dose of 7.5 mg for 4 months.
How more effective was ADT with radiotherapy as compared to radiotherapy alone for patients with localized prostate cancer in this study?
According to the results of this study, the 10-year rate of overall survival was 62% among patients receiving radiotherapy plus short-term ADT (the combined-therapy group) versus 57% among patients receiving radiotherapy alone (hazard ratio for death with radiotherapy alone, 1.17; P=0.03). The addition of short-term ADT was associated with a decrease in the 10-year disease-specific mortality from 8% to 4% (hazard ratio for radiotherapy alone, 1.87; P=0.001).
Morning Report Questions
Q. Which group of patients benefited the most from ADT in this study?
A. The addition of short-term ADT to radiotherapy conferred the greatest clinical benefit in the intermediate-risk subgroup, with an increase in the 10-year rate of overall survival from 54 to 61% and a reduction in the 10-year disease-specific mortality from 10 to 3%.
Q. What are adverse effects of ADT?
A. In prospective studies, short-term ADT caused measurable muscle loss, fat accumulation, decreased insulin sensitivity, and increased cholesterol and triglyceride levels.
@NEJM

Cochrane Review Advises Chemo+RT For Early Hodgkin's

Chemotherapy followed by radiation therapy (RT) is the standard treatment for patients with early-stage Hodgkin's lymphoma, and it should remain so, according to a review published February 16 by the Cochrane Collaboration of Oxford, U.K.

A review of the outcomes of 1,245 patients who participated in five randomized clinical trials, published in the Cochrane Library, sought to answer the question of whether radiation therapy, with its risk of causing secondary cancers from radiation exposure, could be eliminated. The conclusion of the multi-institutional team from Denmark, Germany, and Switzerland was that from a short-term perspective, patients who received both treatments were less likely to die or have local recurrence compared to those who only received chemotherapy.

The clinical trials took place from the 1970s to 2004 and used a variety of chemotherapy agents, as well as diverse doses and types of radiation therapy. Initial responses by patients to treatments were equally effective in eliminating cancer in large part or entirely, according to lead author Christine Herbst, MD, of the department of internal medicine of the University Hospital of Cologne in Germany.
However, data from the meta-analysis identified differences in outcomes when patients were followed between two and 11.4 years. Patients who received the combined treatment were 40% as likely to die compared to those who had chemotherapy alone, and the hazard ratio for tumor control was similar, at 41%. Complete response rates were similar between the treatment groups.
Although adding radiation therapy increased five-year tumor control and overall survival, patients were exposed to radiation doses that could cause secondary cancers 10 to 30 years following treatment, the authors noted. The meta-analysis performed did not evaluate long-term risks.
by : Cynthia E. Keen

Radiation Therapy Comparable To Surgery In Elderly Patients

Stereotactic radiation therapy produces the same survival outcomes for elderly patients diagnosed with early-stage lung cancer as surgery, according to research presented at the 2010 Chicago Multidisciplinary Symposium in Thoracic Oncology held December 9-11.

According to the study, patients who underwent stereotactic radiation therapy had a lower risk of dying within the first 30 days following treatment, even though this was a frailer group of patients compared to controls. The research was conducted by a team from Amsterdam's VU University Medical Center, the Comprehensive Cancer Center, and the Netherlands Cancer Institute.

The group conducted a matched-pair analysis of the overall survival outcomes of patients living in north Holland who received treatment after being diagnosed with stage I non-small cell lung cancer (NSCLC) between 2005 and 2007. A total of 191 patients were identified from a comprehensive population-based registry. From this group, a total of 122 patients could be matched, half of whom had surgery and half of whom had stereotactic body radiation therapy (SBRT) treatments.

The median age of the patients at the time of diagnosis was 79 years. Patients were matched by age, gender, year of treatment, and T-stage. Baseline co-morbidities were not available, but a large number of patients who received the stereotactic radiation therapy were medically inoperable, according to lead author and presenter David Palma, MD, a radiation oncologist who conducted the study while on a research fellowship at VU University Medical Center. Palma is now practicing at the London Regional Cancer Program in London, Ontario.

Patients were followed for a median of 43 months. Six patients died within the first 30 days following treatment; five of these patients had undergone surgery. Overall survival at one year was 75% for surgical patients and 87% for radiation therapy patients. Three years following treatment, 60% of the surgery group and 41% of the radiation therapy group were alive.

"Many would expect that the patients treated with radiation therapy would do worse than those undergoing surgery," Palma told attendees at the American Society for Radiation Oncology (ASTRO)-sponsored symposium.

"At the time that these patients underwent treatment, patients only received radiation if they were too unwell for surgery or if they refused surgery," he continued. "Because most of these radiation therapy patients had medical problems that prevented them from having surgery, we would expect them not to live as long as the surgery patients. Yet, despite this disadvantage, the radiation therapy patients lived just as long as the healthier patients who had surgery for the first 12 months following treatment."

Up to one-fourth of Dutch patients older than 75 who are diagnosed with stage I and stage II NSCLC do not receive any oncologic therapy, Palma said. Stereotactic body radiation therapy is an attractive treatment option for surgically unfit and/or elderly patients, due to its ease of administration and favorable toxicity profile, he explained.

"Patients prefer this treatment because there is no hospitalization associated with it, it doesn't require an anesthetic, there is no risk of infection from a surgical procedure, and it only takes a few treatments," Palma added:"I think that the use of stereotactic body radiation therapy will increase," he added. "We've seen over the past five years already that elderly patients and their physicians are choosing radiation more often to treat stage I lung cancer, and fewer patients are choosing to go without treatment as well. This study shows us that the stereotactic treatment is effective even for patients who have many medical problems."

A comparison of the costs of each treatment was not in the scope of the study. However, Palma said that cost-effectiveness studies are currently being performed, though results are not yet available. "In most countries with socialized medicine, once radiation therapy equipment has been purchased, the cost of radiation treatment is relatively inexpensive," he concluded.

By Cynthia E. Keen
AuntMinnie.com staff writer
December 17, 2010