Glioblastoma Patients Treated With Bevacizumab Experience Reduced Cognitive Function And Quality Of Life

Main Category: Neurology / Neuroscience
Also Included In: Cancer / Oncology
Article Date: 04 Jun 2013 - 0:00 PDT Current ratings for:
Glioblastoma Patients Treated With Bevacizumab Experience Reduced Cognitive Function And Quality Of Life

Many glioblastoma patients treated with bevacizumab (AvastinR) have significant deterioration in neurocognitive function, symptoms and quality of life. Not only that, the changes often predict treatment outcomes, according to new research from The University of Texas MD Anderson Cancer Center.

The findings from the large national multi-center Phase III trial, RTOG 0825, were presented at the annual meeting of the American Society of Clinical Oncology.

Glioblastoma is the most frequent and aggressive type of brain tumor. Despite slight gains, tumors pose a high risk of recurrence and are commonly fatal.

Previous studies found bevacizumab, a monoclonal antibody directed against the vascular endothelial growth factor, prolongs progression-free survival (PFS) in patients with recurrent glioblastoma.

RTOG 0825, one of the largest trials to study the clinical benefit of a brain tumor treatment, evaluated newly diagnosed patients treated with bevacizumab, in addition to standard chemoradiation and maintenance temozolomide, versus those who received a placebo and standard treatment.

Tests measured effects of treatment

Using objective tests of cognitive function and subjective measures of symptoms and quality of life, 507 patients were evaluated at diagnosis and at intervals throughout treatment as long as scans showed their tumors were not progressing.

"Most studies rely on traditional endpoints, including overall survival and radiographic outcomes, such as PFS, with little attention to the impact of the disease and therapies on the patient," said Jeffrey Wefel, Ph.D., associate professor in MD Anderson's Department of Neuro-Oncology and a senior author on the study. "This makes the potential clinical benefit difficult to ascertain."

Neurocognitive changes

At the beginning of the study, patients' neurocognitive function in both groups was below healthy population norms. Longitudinal analyses showed those treated with bevacizumab compared to ones treated with placebo demonstrated greater decline in global neurocognitive function, executive function (skills involved in tasks such as planning, organizing and multi-tasking) and processing speed.

Additionally, baseline performance and early change (through week 10) in global neurocognitive function, memory, executive function and processing speed were prognostic for survival.

"Relatively little attention has been directed toward investigating patient biomarkers associated with outcomes," Wefel said. "We sought to determine if patient cognitive function was a biomarker associated with progression-free and overall survival (OS) time. We found patients with worse cognitive function at baseline, and those who experienced cognitive decline after concurrent chemoradiation with or without bevacizumab, were at greater risk for shorter PFS and OS time."

Quality of life and side effects

Symptoms and quality of life were significantly worse for patients receiving bevacizumab, particularly at weeks 22 and 34. In particular, symptom burden, including treatments, and generalized and affective symptoms were greater, with persistent differences seen in treatment-associated symptoms. Additionally, overall symptom burden, tumor and treatment-related symptoms, as well symptoms that interfered with daily activities, were also worse for those on bevacizumab over the treatment course.

Baseline and early change rating of both symptoms and quality of life, like neurocognitive function, were also prognostic for survival.

"The idea of our research was to put together the total picture of this treatment, not only how it affects the tumor, but how it affects patients and how they go about their lives," said Terri Armstrong, Ph.D., adjunct professor in MD Anderson's Department of Neuro-Oncology. "It was our hope this treatment would improve life for them, but that just wasn't the case. For many, both tumor and treatment-related symptoms were worse and continued to get worse over time."

Next steps

"We're eager to continue investigating the data within this trial to identify subsets of patients for whom a particular therapeutic approach may have been associated with a favorable net clinical benefit for survival, cognition, symptoms and quality of life," Wefel said.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our neurology / neuroscience section for the latest news on this subject. Support sources for the study include Radiation Therapy Oncology Group (RTOG) grants U10 CA21661 and U10 CA37422 and Genentech, Inc.

Disclosures: Wefel serves on Genentech's advisory board and is a consultant to Roche. Armstrong also serves on Genentech's advisory board.

In addition to Wefel and Armstrong other MD Anderson authors on the study include Mark Gilbert, M.D. and Ritsuko Komaki, M.D. Other authors include: Stephanie Pugh, Ph.D. and Minhee Won, MA Radiation Therapy Oncology Group; Merideth Wendland, M.D., Willamette Valley Cancer Institute; David Brachman, M.D., Arizona Oncology Services; Ian Crocker, M.D., Emory University; H. Ian Robins, M.D., Ph.D., University Wisconsin Madison; R. Jeffrey Lee, M.D., Intermountain Medical Center; and Minesh Mehta, M.D., University of Maryland Medical Center.

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University of Texas M. D. Anderson Cancer Center

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Sexual Function an Issue for Breast Cancer Survivors

About 70% of breast cancer survivors reported in a recent study that they had difficulty having sex, according to an article published in the Journal of Sexual Medicine.

The many physical and emotional changes that follow a cancer diagnosis can affect sex and intimacy. Two of the most common sexual concerns expressed by women after a cancer diagnosis are loss of libido and vaginal dryness.

Factors that may influence the likelihood of sexual problems among breast cancer survivors include body image (which may vary by type of surgery) and hormonal therapies such as aromatase inhibitors.

To better understand how a breast cancer diagnosis and treatment affects sexual function and body image, researchers evaluated 1,011 women who had been diagnosed with breast cancer within a year of the study.

70% of participants reported sexual dysfunction.Factors associated with a higher incidence of sexual dysfunction included being postmenopausal, experiencing menopausal symptoms, and using aromatase inhibitors. 77% of participants reported menopausal symptoms, which made them twice as likely to experience problems with sexual function. This association was strongest among women taking aromatase inhibitors.Body image issues were associated with a higher rate of sexual dysfunction.Treatment with tamoxifen was not associated with a higher rate of sexual dysfunction.

A majority (70%) of breast cancer survivors in this study experienced problems with sexual function. The researchers conclude that sexual dysfunction is more common among women taking aromatase inhibitors, as use of these drugs may cause menopausal symptoms, such as vaginal dryness, which may make intercourse painful and less pleasurable overall. Because problems such as vaginal dryness can be treated, women are advised to discuss concerns about sex and sexuality with their healthcare provider. Women may also find it helpful to talk openly with their partners about how their sexual needs have changed. It is also important to note that some women without a history of breast cancer complain of sexual dysfunction, so some of the symptoms reported may not be attributable to breast cancer and/or it’s treatment.

Reference: Panjari M, Bell RJ, and Davis SR. Sexual function after breast cancer. Journal of Sexual Medicine [early online publication]. September 23, 2010.

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Ovarian Suppression During Chemotherapy Fails to Improve Post-Treatment Menstrual Function

Among young women undergoing chemotherapy for breast cancer, use of the drug triptorelin to suppress ovarian function during treatment does not appear to improve post-treatment menstrual function. These results were published in the Journal of Clinical Oncology.???

Fertility preservation is increasingly being recognized as an important issue for young people with cancer. In premenopausal women, many chemotherapy drugs are toxic to the egg cells (oocytes) in the ovaries. If the number of remaining oocytes in the ovaries reaches a critically low point during treatment, women experience “acute ovarian failure.” This means that the ovaries stop functioning during or shortly after cancer treatment. If oocytes are lost during treatment but do not reach this critically low point, women are at risk for early menopause but may still be able to get pregnant for some time after treatment.????

Freezing embryos prior to cancer treatment is one of the most well established approaches to fertility preservation in young women, but is not always an option. One of the alternative approaches being evaluated involves the use of drugs known as gonadotropin-releasing hormone (GnRH) agonists to suppress ovarian function during chemotherapy. The hope is that this will protect the ovaries and improve post-treatment ovarian function.????

To explore the effects of the GnRH agonist triptorelin during chemotherapy for breast cancer, researchers conducted a study among premenopausal women age 44 or younger. Study participants were assigned to receive either triptorelin or a placebo. The study was originally designed to enroll 124 women, but it was stopped after only 49 women were enrolled because preliminary results indicated no benefit from triptorelin.????

Menstruation resumed in 88 percent of women in the triptorelin group and 90 percent of women in the placebo group.?Menstrual cycles resumed after a median of 5.8 months in the triptorelin group and 5.0 months in the placebo group.?

These results suggest that triptorelin does not improve post-treatment menstrual function in young breast cancer patients. Other, ongoing studies will provide more information on this topic.? ?

Premenopausal women who are interested in preserving their fertility during cancer treatment are advised to discuss their options with their physician before treatment begins.?????

Reference: Munster PN, Moore AP, Ismail-Khan R et al. Randomized trial using gonadotropin-releasing hormone agonist triptorelin for the preservation of ovarian function during (neo)adjuvant chemotherapy for breast cancer. Journal of Clinical Oncology. Early online publication January 9, 2012.?

Posted January 13, 2012?

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