Mr. Susman is a freelance medical writer based in Florida, USA. He travels worldwide to report from medical conferences, writing regularly for wire services, internet websites, and medical journals such as the Journal of the National Cancer Institute and AIDS.
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SINGAPORE – Researchers here suggested that cancer patients undergoing chemotherapy may have worse outcomes if they are depressed because levels of brain-derived neurotrophic factor (BDNF) are decreased in these individuals – and that protein affects responsiveness to the anti-cancer treatments,
“Depression can reduce the effects of chemotherapy and BDNF plays an important role in this process,” said Yufeng Wu, MD, head of oncology at Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, in China.
In her study, presented at the second annual ESMO Asia Congress, Dr. Wu said, “It’s crucial doctors pay more attention to the mood and emotional state of patients.
The researchers study 186 newly diagnosed patients receiving chemotherapy. To assess their state of mind, they were asked to rate their depression levels the day before treatment began. Quality of life details, overall survival and other data were also collected. This allowed researchers to compare this information with the patients’ mood scores.
Results showed that those whose cancer had spread to other organs were the most depressed and this severely decreased their tolerance to chemotherapy. It was associated with vomiting, a reduction in white blood cells, and prolonged hospital stays. The impact of severe depression was even greater. It reduced the length of time that patients lived with the disease without it getting worse.
Researchers found that BDNF clearly boosted the number of tumor cells killed by chemotherapy. Patients with severe depression had lower levels of the protein in the blood so their bodies were not as effective at fighting cancer. This reduced their chance of surviving the disease.
“Our aim now is to prescribe drugs such as fluoxetine to depressed patients and study their sensitivity to chemotherapy,” added Dr. Wu.
Commenting on the results of the research, Ravindran Kanesvaran, consultant medical oncologist and assistant professor, Duke-NUS Medical School, Singapore, said: “The link between depression and poor outcomes among these patients is significant and can be associated with the down-regulation of brain derived neurotrophic factor.
“This finding can perhaps lead to new ways to treat depression in these patients which in turn may prolong their lives,” Dr. Kanesvaran said. “Further research is needed to establish the effects of different anti-depressant drugs on BDNF levels.”
New agent effective in breast cancer
In another study at the meeting, researchers suggested that the targeted agent ribociclib significantly improves progression-free survival in Asian women with advanced breast cancer.
“Breast cancer is a significant health burden in Asia, with 24 percent of cases worldwide diagnosed in this region alone,” said Yoon-Sim Yap, MD, senior consultant in medical oncology at the National Cancer Centre Singapore.
Endocrine therapy is the backbone of treatment for hormone receptor-positive breast cancer but efficacy is often limited by de novo or acquired resistance. Disease progression eventually occurs in most patients receiving endocrine therapy. The CDK4/6 pathway is implicated in endocrine therapy resistance, and therefore, combined endocrine and CDK4/6-targeted therapy may prolong treatment benefit and delay the use of chemotherapy.
In MONALEESA-2, a phase 3 randomized trial, postmenopausal women diagnosed with hormone receptor positive, NER2-negative advanced breast cancer were assigned to receive either ribociclib – a CDK4/6 inhibitor — plus endocrine therapy with letrozole or placebo plus letrozole for the first-line treatment.
Dr. Yap and colleagues assigned 334 patients to each treatment group. In a pre-defined subgroup of Asian patients, the addition of ribociclib to letrozole increased progression free survival of 70% among those whose homes were in Asia and by 61% among the patients in the study who self-identified as Asian.
Combined ribociclib and letrozole treatment was well tolerated in Asian patients, with a similar safety profile as that observed in the full population, the researchers said.
Dr Yap said: “First-line ribociclib and letrozole significantly prolonged PFS compared to placebo plus letrozole with an acceptable safety profile in postmenopausal Asian women with HR-positive, HER2-negative advanced breast cancer. This trial shows that the combination of ribociclib and letrozole is an effective first-line therapy for HR-positive advanced breast cancer, including for the Asian patient population.”
Commenting on the findings, Dr Sing-Huang Tan, senior consultant in hematology-oncology at the National University Cancer Institute, Singapore, said, “This predefined subgroup analysis reaffirms the data obtained in the Western population and provides further evidence that ribociclib in combination with letrozole also demonstrates efficacy in Asians. It highlights another alternative to the various therapies already available, and may serve as an additional combination therapeutic option to those with a higher burden of disease for which endocrine therapy is still deemed appropriate.”
Blood test gives prognosis
A routine blood test can predict how long cancer patients in palliative care will survive, reported Japanese researchers in another study at the congress.
“Cancer patients in palliative care want honest and accurate prognostic information but this information needs to be shared sensitively and in a way that respects their desire to maintain hope,” said Yu Uneno, MD, an oncologist at Kyoto University.
“Patients with advanced cancer and their families have to make decisions about treatment, where to spend the end-of-life, and when to discontinue palliative chemotherapy,” said Dr. Uneno. “Continuing ineffective therapy increases life-threatening adverse events, reduces quality of life, delays hospice referral, and deprives patients of the chance to die in their preferred place. Accurately predicting prognosis improves end-of-life care for cancer patients and their caregivers.”
The researchers suggested that use of the Six Adaptable Prognostic models which use 3 laboratory measurements – albumin, neutrophil count and lactate dehydrogenase which are routinely monitored in daily clinical practice with a blood test – may be an improved over subjective clinical assessment.
The models can be used at any time point after the initiation of treatment – an important feature since a patient’s condition can change, Dr. reported. The six models were developed in approximately 5,000 cancer patients receiving chemotherapy at Kyoto University Hospital. They predicted death within 1–6 months for patients with cancer receiving chemotherapy, allowing physicians to re-estimate prognosis at any time point after the initiation of chemotherapy.
Survival evaluations can determine whether pharmacological treatment should be given. Cytotoxic chemotherapy would rarely be prescribed in a patient unlikely to survive beyond several weeks because of unpleasant side effects. The sedative midazolam is used for symptom relief in palliative care settings, but tolerance can develop if administered for two weeks or longer. Chronic midazolam treatment could therefore be recommended only for patients likely to die within a few weeks, and be contraindicated when predicted survival was longer than a month.
The current study tested the predictive value of the models in cancer patients receiving palliative care. It was designed as a sub-analysis of the Japan–prognostic assessment tools validation (J-ProVal) study, which compared the ability of four models to predict survival of advanced cancer patients in the real world.
This sub-analysis included 1,015 patients, of whom 385 were based with palliative care teams in hospital, 464 were in palliative care units, and 166 were receiving palliative care services at home. The investigators performed receiver operating characteristic analysis to calculate the ability of the SAP models to predict death in cancer patients in the palliative care setting. The area under the curve (AUC) for predicting death within 1–3 months ranged from 0.75 to 0.80.
Dr. Uneno said: “We found that the SAP models had a good ability to predict that a patient would die in one to three months. The prediction was accurate in 75–80% of cases. The SAP models could be a promising decision aid for healthcare professionals and patients. Accurate prediction of survival allows patients adequate time to prepare for their impending death and is vital for planning effective palliative care.”
Commenting on the findings, Grace Yang, MD, consultant in palliative medicine at the National Cancer Centre, Singapore, said, “The rapidly increasing armamentarium of anti-cancer therapy means that cancer patients can receive multiple lines of chemotherapy, immunotherapy or targeted therapy. Cancer patients may have aggressive treatment until the very last days of life, not without physical symptoms and great financial cost. Information about a cancer patient’s prognosis will help weigh the benefits and burdens of further cancer-directed treatment.
“Knowing the patient’s prognosis will facilitate decision making regarding trade-offs, not only for anti-cancer therapy, but for treatments directed at relieving symptoms,” she said.
“For example, in deciding between pain-relieving treatments with different time horizons for onset and duration of effect, with different side effects/risk profiles and different financial costs. As we get closer to knowing how long a cancer patient has to live, further studies exploring the ethical and psychological implications will also be worthwhile,” Dr. Yang said.
January 2017 Health and Lifestyle