OncoBriefs: Local Tx for mRCC, Cervical Ca Prevention (CME/CE)

Editor’s note: This article describes three separate new findings in cancer research. The first is relevant for people with metastatic renal cell carcinoma (mRCC). Researchers have found that image-guided local ablation of tumors still has an important treatment role, even though there have been recent improvements in mRCC drugs. The second finding concerns people with metastatic neuroendocrine tumors (NETS). A clinical trial with volunteer patients found promising results for patients treated with the new drug lanreotide (aka Somatuline). The third finding has to do with preventing cervical cancer in women at high risk for the disease. The women involved in the study had high-grade cervical intraepithelial neoplasia (CIN 2/3), and were treated with surgical removal of the squamocolumnar junction (SCJ). These women had only low-grade recurrences, suggesting that removing SCJ cells might help prevent cervical cancer.

“More than 80% of patients with metastatic renal cell carcinoma (mRCC) remained alive without disease progression 3 years after image-guided local ablation of tumors, a retrospective study showed.

“Six of 76 evaluable tumors recurred an average of 1.6 years from treatment. Local ablation represents a “relatively safe procedure with acceptable local control rates,” authors concluded in an article published in the August issue of the Journal of Urology. A summary of the article leads off this edition of OncoBriefs, which also examines a somatostatin derivative for neurendocrine tumors and a surgical approach to cervical cancer prevention.”

Race Affects Opioid Selection for Cancer Pain

“Racial disparities exist in the type of opioid prescribed for cancer pain, according to a study published online July 21 in the Journal of Clinical Oncology.

“Salimah H. Meghani, Ph.D., R.N., from the University of Pennsylvania in Philadelphia, and colleagues recruited 182 patients from clinics within a single health system. All participants reported the presence of cancer-related pain plus a prescription for morphine or oxycodone. The abbreviated Modification of Diet in Renal Disease formula was used to estimate kidney function.

“The researchers found that the severity of analgesic-related adverse effects was greater for patients with chronic kidney disease (CKD) who received morphine versus oxycodone (P = 0.010). Compared with white patients, African-American patients had 71 percent lower odds of receiving a prescription of oxycodone (P < 0.001), when controlling for health insurance type. The effect of private insurance was no longer significant on limiting the analysis to patients with CKD, but race remained a significant predictor of the prescribed opioid selection. In the presence of CKD, race was a strong predictor for adverse effect severity, and this association was partially mediated by the type of opioid selection.”

Drugs to Avoid in Patients on Tyrosine Kinase Inhibitors

Editor’s note: More and more people with cancer are being treated with drugs known as tyrosine kinase inhibitors (TKIs). As with any other drug, oncologists who prescribe TKIs must be aware of other drugs a patient is taking to ensure there will not be a dangerous drug-drug interaction. Researchers recently published a report outlining known and potential drug-drug interactions between TKIs and other drugs. Oncologists and patients may wish to take these into account when considering cancer treatment with TKIs.

“With the rapid and widespread uptake of tyrosine kinase inhibitors (TKIs) in oncology over the past several years, serious drug–drug interactions are an “increasing risk,” according a new report.

“To guarantee the safe use of TKIs, ‘a drugs review for each patient is needed,’ write Frank G.A. Jansman, PharmD, PhD, from Deventer Hospital in the Netherlands, and colleagues in a review published in the July issue of the Lancet Oncology.

“The review provides a comprehensive overview of known and suspected interactions between TKIs and conventional prescribed drugs, over-the-counter drugs, and herbal medicines.

“All 15 TKIs approved to date by the US Food and Drug Administration or the European Medicines Agency are evaluated.

“They are axitinib (Inlyta, Pfizer), crizotinib (Xalkori, Pfizer), dasatinib (Sprycel, Bristol-Myers Squibb and Otsuka America), erlotinib (Tarceva, Osi Pharmaceuticals), gefitinib (Iressa, AstraZeneca), imatinib (Gleevec, Novartis), lapatinib (Tykerb, GlaxoSmithKline), nilotinib (Tasigna, Novartis), pazopanib (Votrient, GlaxoSmithKline), regorafenib (Stivarga, Bayer), ruxolitinib (Jakafi, Incyte), sorafenib (Nexavar, Bayer), sunitinib (Sutent, Pfizer), vandetanib (Caprelsa, AstraZeneca), and vemurafenib (Zelboraf, Roche).”

Living With Cancer: A Tour of Hospice

“Before the visit, I had been split in two not by fear of death but by dread of dying — in anxiety, dementia, but mostly in pain from recurrent ovarian cancer.

“My mind was always running on two tracks. On one track, I attended to whatever actual event was occurring, be it an outing to the library or the making of a meal. The simultaneous second track was psychic or psychotic, depending on your point of view, but invariably chilling. It took me to scenes of the degeneration that would ensue after the targeted drug I am taking stopped working.

“So I welcomed the idea suggested by a member of my cancer support group: that we tour the new hospice facility where our friend Leslie had died. “Not a recruitment visit, just a field trip,” we joked as we decided to invite our partners to join us in meeting with the co-director of Hospice House, Dr. Robert Stone.

“On a fearfully cold day, we drove to a lodge on a wooded lot at the edge of our small town. By a blazing fireplace surrounded by comfortable chairs, about 10 of us amassed — six women dealing with gynecological cancer and some of our husbands. We were quiet because the family of a patient was using the adjacent kitchen.”

Image: iStock

Dutch Phase II Study Supports Phase III Evaluation of Bevacizumab Plus Lomustine, but Not Bevacizumab Alone, in Recurrent Glioblastoma

The gist: Researchers conducted a clinical trial with volunteer patients to test two drugs, alone and in combination, for recurrent glioblastoma. The two drugs tested were bevacizumab (aka Avastin) and lomustine (aka CeeNU). The researchers found promising results for patients who took both bevacizumab and lomustine, and recommend that further clinical trials be conducted to continue to study the new combination treatment. The patients who participated in the study all had glioblastoma that was treated with temozolomide chemoradiotherapy, but recurred.

“Bevacizumab (Avastin) is frequently used in patients with recurrent glioblastoma, although it is unclear whether responses observed with such treatment result in improved overall survival. In the phase II Dutch BELOB study reported in The Lancet Oncology, Taal et al found that overall survival results supported phase III evaluation of the combination of bevacizumab and lomustine (CeeNU) but not bevacizumab monotherapy…

“In this open-label trial, 153 adult patients from 14 Dutch hospitals with a first recurrence of glioblastoma after temozolomide chemoradiotherapy were randomly assigned between December 2009 and November 2011 to receive oral lomustine at 110 mg/m2 once every 6 weeks, intravenous bevacizumab at 10 mg/kg once every 2 weeks, or combination treatment at the same doses. The primary endpoint outcome was overall survival at 9 months in the intent-to-treat population.

“A preplanned safety analysis after eight patients had received the combination regimen showed that three had grade 3 and two had grade 4 thrombocytopenia, with these toxicities requiring a reduction in bevacizumab dose intensity. The lomustine dose in the combination group was subsequently reduced to 90 mg/m2. In addition to the eight combination recipients getting the higher lomustine dose, 51 received bevacizumab alone, 47 received lomustine alone, and 47 received bevacizumab plus lomustine at 90 mg/m2.

“The investigators concluded, ‘The combination of bevacizumab and lomustine met prespecified criteria for assessment of this treatment in further phase 3 studies. However, the results in the bevacizumab alone group do not justify further studies of this treatment.’ ”

Emesis Combo Quells CINV in Three Trials (CME/CE)

The gist: Some cancer patients who are treated with chemotherapy experience nausea and vomiting as side effects. Researchers recently conducted three clinical trials with volunteer patients to test a treatment for chemotherapy-induced nausea and vomiting (CINV). The trials compared two different dosing schedules of a treatment that combines the drugs netupitant and palonosetron (aka Aloxi). The researchers reported that a single-dose schedule solved the CINV problem for more patients than a multidose schedule.

“A single-dose antiemetic regimen provided superior control of chemotherapy-induced nausea and vomiting (CINV) as compared with a standard multidose regimen, according to results of three randomized trials.

“In each trial, the fixed-dose combination of netupitant and palonosetron (Aloxi) led to a significantly higher rate of complete response during the delayed phase of the first cycle of chemotherapy versus control regimens. Complete response rates with netupitant-palonosetron (NEPA) regimen ranged from 76% to 89%, representing absolute differences of 5% to 14% versus the control groups.

“Taken together, results of the three trials suggest a ‘winning team’ in the search for optimal management of CINV, reported Matti Aapro, MD, of the Multidisciplinary Oncology Institute in Genolier, Switzerland, and colleagues in the July issue of Annals of Oncology.

” ‘If the present registration trial results are replicated in the “real” clinical world, then the NEPA formulation appears to be an advance in terms of overall efficacy and simplicity of dosing regime with the maintenance of efficacy over multiple cycles of chemotherapy being particularly encouraging,’ Paul L.R. Andrews, PhD, of St George’s University of London, said in an accompanying editorial.”

No Clinical Outcome Benefit With Aerobic Training Program in Cancer Patients With Heart Failure

The gist: Researchers conducted a clinical trial with volunteer patients to test the effects of a program of aerobic training on cancer patients with heart failure. They found that the aerobics program did not reduce the rate of mortality or hospitalization for patients, but patients who were able to adhere to the program seemed to have better clinical outcomes.

“In a retrospective analysis in the HF-ACTION trial reported in the Journal of Clinical Oncology, Jones et al found that a program of aerobic training did not reduce the rate of all-cause mortality or hospitalization in cancer patients with heart failure. Some evidence suggested that patients who were able to adhere to the program had improved outcomes…

“The study evaluated the primary endpoint of all-cause mortality or hospitalization among 47 patients randomly assigned to aerobic training and 43 to guideline-based usual care in the HF-ACTION trial. Patients had to have medically stable heart failure. The aerobic training program consisted of three supervised 20- to 45-minute sessions at 60% to 70% of heart rate reserve each week for 12 weeks followed by home-based sessions for 4 to 12 months…

“The investigators concluded, ‘In [intention-to-treat] analyses, [aerobic training] did not improve clinical outcomes in patients with cancer who had [heart failure]. Post hoc analyses suggested that patients not capable of adhering to the planned [aerobic training] prescription may be at increased risk of clinical events.’ ”

Promising Medication Counteracts Constipation Caused by Opioid Painkillers

“Up until a decade ago, physicians rarely prescribed opioids, reserving them primarily for the terminally sick. Today, opioid-based drugs have proliferated thanks to their ‘user-friendliness’ and effectiveness. Millions of patients take opioids on a daily basis to manage lower back pain and chronic joint problems. Opioids also play a critical role in pain management regimes for cancer patients.

“However, opioids have a number of side effects, including nausea, vomiting and — notoriously — constipation. Opioids block pain by binding to ‘mu-receptors’ in the brain. But they also bind to mu-receptors in the bowels, and this causes constipation.

“Some sixty percent of patients that take opioid pain relievers experience constipation. For some, the bother is so great that they choose to stop taking the drug…

“A newly developed opioid antagonist called naloxegol may offer relief. Stage 3 testing by an international team of researchers led by Belgian gastroenterologist Jan Tack (University Hospitals Leuven) confirms the drug’s efficacy.”

Growing Participation in Novartis' Signature Program Bodes Well for Novel PGx Signal Finding Approach

The gist: The Signature Program lets people with different kinds of cancer across the U.S. access new, promising drugs that are still in the testing phase (i.e. they cannot yet be simply prescribed by oncologists). The program matches patients to different treatments based on the distinct genetic changes found in each patient’s tumor. According to this article, Signature is enrolling an “encouraging” amount of patients. And, it may be driving more oncologists at community healthcare settings to use molecular testing to help patients choose their best treatment options. Learn more about Signature at our Need to Know blog.

“Participation in Novartis’ biomarker based signal-finding trials, known as the Signature Program, is progressing at an encouraging pace, according to researchers involved in the effort.

“Novartis last year launched the Signature Program, a drug trial series in which patients are enrolled into mutation-specific study protocols that are tissue agnostic. Currently, cancer drugs are studied and approved according to a specific tumor site or histology (ie. breast cancer, lung cancer, etc). However, with advances in genomic knowledge, life sciences experts have often discussed future scenarios where therapies will be studied in and approved for the specific molecular pathways they interrogate. Novartis is taking the first step toward exploring such a vision through the Signature Program.”