Even for just a few months, the use of androgen deprivation therapy to treat men with prostate cancer that hasn't metastasized may significantly increase the risk of diabetes and cardiac-related effects, including heart attack, according to a study in the September 20 Journal of Clinical Oncology (JCO).
Conducted by Dr. Nancy L. Keating and colleagues of Harvard Medical School and Brigham and Women's Hospital, the observational study followed more than 73,000 men 66 years of age or older who were diagnosed with locoregional prostate cancer between 1992 and 1999. More than one-third of the men in the study received a gonadotropin-releasing hormone (GnRH) agonist, while approximately 7 percent of the men underwent a complete orchiectomy (surgical removal of the testicles).
GnRH agonist use was associated with a 44-percent increased risk of patients developing diabetes, with smaller - yet still statistically significant - increases in the risk of heart attack, coronary heart disease, and sudden cardiac death. Although diabetes risk also was significantly increased with orchiectomy, it did not appear to have the same cardiac effects. Because so few men underwent this procedure, the authors cautioned, the study may have been underpowered to detect such a risk.
The increased diabetes and cardiac risks associated with GnRH agonist use appeared as early as 1 to 4 months after treatment initiation.
"Our findings suggest that, for men who require GnRH agonist therapy, strategies to mitigate modifiable risk factors for diabetes and coronary heart disease may be warranted," they concluded.
Dr. Lori Minasian of NCI's Division of Cancer Prevention (DCP) cautioned that the study may have been unable to account for preexisting comorbidities in the study population. "So it's too soon to say from this study alone that there is a clear increase in risk," she said.
A phase III randomized trial has shown a statistically significant improvement in progression-free survival for women with platinum-sensitive recurrent ovarian cancer given gemcitabine with carboplatin compared with carboplatin alone, without any significant differences in quality of life. The results, published early online September 18 in JCO, come from an international collaborative trial comprising investigators from Europe, Canada, and the United States.
Investigators randomly assigned 356 women with recurrent ovarian cancer whose tumors had previously responded to first-line therapy with a platinum-based regimen to receive either carboplatin alone or carboplatin plus gemcitabine, and compared progression-free survival, side effects, and overall quality of life.
Though more high-grade hematologic side effects and a greater incidence of alopecia (hair loss) were seen in patients taking carboplatin and gemcitabine, few patients in either arm discontinued treatment. The median progression-free survival was 8.6 months for patients taking carboplatin and gemcitabine, and 5.8 months for patients taking carboplatin alone. The benefit provided by the addition of gemcitabine persisted even after adjusting the data for other factors that could affect progression-free survival. Quality-of-life questionnaires showed no statistically significant differences between the two groups of patients.
"Gemcitabine plus carboplatin represents a new treatment option for patients with platinum-sensitive recurrent ovarian cancer," stated the authors. Such new therapeutic regimens are badly needed, they explained, because cumulative neurotoxicity limits the reuse of taxane and platinum combinations often used as first-line therapy in the disease.
Aromatase inhibitors (AIs) have proven superior to tamoxifen as a hormonal treatment for early-stage breast cancer in women with estrogen-sensitive tumors. The third generation of these agents - letrozole, anastrozole, and exemestane - is also widely used to treat advanced or metastatic breast cancer, though clinical results about their value in that setting have been mixed. Researchers from Greece analyzed published trials and found that third-generation AIs provide a definite, if small, overall survival advantage.
"Our results may represent a departure from the standard management of advanced breast cancer with hormonal therapy that has been used for the last two decades," wrote Dr. John P.A. Ioannidis of the University of Ioannina School of Medicine and colleagues in the September 20 Journal of the National Cancer Institute (JNCI). "The standard of care may need to be reconsidered."
The AIs reduced the risk of death by 13 percent - about 5 months more life in women whose median survival is projected to be 40 months. Though they may produce more hot flashes, the AIs are generally more tolerable than tamoxifen and also improve quality of life.
In an accompanying editorial, Drs. Catherine H. Van Poznak and Daniel F. Hayes of the University of Michigan agree that AIs are the drug of choice for women with endocrine-responsive metastatic breast cancer, without ruling out some use of tamoxifen. They cite surveys of oncology practice patterns which show that only about half of these women will receive AIs as adjuvant therapy, despite a recent recommendation by the American Society of Clinical Oncology (ASCO).
Although rates of surgery for renal cancer have increased with the rising incidence of this malignancy over the last 20 years, a new study published in the September 20 JNCI suggests that a corresponding increase in survival has not been realized.
Investigators from the University of Michigan collected data from 34,503 patients with kidney cancer recorded in the Surveillance, Epidemiology, and End Results (SEER) registries from 1983 to 2002, and compared yearly incidence of the disease, incidence of renal surgery, pretreatment tumor size, and demographic data.
Their results showed an increase in the incidence of kidney cancer from 7.1 per 100,000 U.S. population to 10.8 per 100,000 - an increase of 52 percent. This was attributed largely to an increase in small (≤4 cm) renal tumors, which are now often found incidentally during newer, more powerful diagnostic procedures for other conditions. "This increase in incidence of the small renal mass has been paralleled by an increase in surgical treatment," explained the authors. However, despite the increased incidence of surgery, kidney-cancer-specific and overall mortality for patients still rose by 155 percent and 323 percent, respectively.
"Despite increased detection and treatment of small masses, mortality rates for kidney cancer have continued to rise. Collectively, these trends raise questions about the effectiveness of the current treatment paradigm for kidney cancer," stated the authors. They suggest that a proportion of small kidney tumors may be a more indolent form of renal cell carcinoma that "may not merit surgical removal."
Women 75 or older with early-stage breast cancer are more likely to receive nonstandard primary tumor therapy in an integrated health care setting, reported a study in the September 18 JCO.
Dr. Rebecca Silliman of Boston University Medical Center and colleagues identified 1,859 women 65 years of age or older with stage I and II breast cancer between 1990 and 1994 from 6 geographically diverse integrated health systems of the Cancer Research Network. Using SEER cancer registries, as well as clinical and administrative databases, researchers collected data on demographics, tumor characteristics, breast cancer treatment, and comorbid conditions prior to diagnosis.
Researchers then compared women who received standard primary tumor therapy, defined as axillary lymph node dissection and radiation therapy after breast-conserving surgery (BCS), with women who received nonstandard primary tumor therapy. They also compared women who received a tamoxifen prescription or chemotherapy with women who did not.
Women with higher comorbidity index scores, and women 75 or older, were more likely to receive nonstandard primary tumor therapy. While risk of recurrence was also associated with receipt of nonstandard primary tumor therapy, no link exists for standard primary tumor therapy. Additionally, researchers found that African American women were less likely to be prescribed tamoxifen and Asian women were more likely to undergo BCS than were white women.
The study's authors concluded that "Age is an independent risk factor for nonreceipt of effective therapies, even when comorbidity and risk of recurrence are considered."An accompanying editorial by Dr. Jeanne Mandelblatt of the Lombardi Comprehensive Cancer Center in Washington, D.C., noted that, "What we need is an understanding of the biology of cancer in this population [women 65 or older with breast cancer], tools that can help clinicians identify physiological reserve and ability to withstand the rigors of more aggressive treatment, and more consistent elicitation of women's informed preferences."