With the growing number of cancer survivors in the United States and around the world, supportive care has become of even greater importance for these patients. At the recent Multinational Association of Supportive Care in Cancer (MASCC) annual meeting, held June 27-29, 2013, in Berlin, Germany, more than 1400 attendees could choose from a wealth of presentations to enhance their knowledge of supportive care and improve cancer care outcomes. Below are selected brief summaries of highlights from the meeting.
Prophylactic Subcutaneous Fentanyl for Dyspnea
A preliminary double-blind, randomized, controlled clinical trial suggests that prophylactic use of subcutaneous fentanyl can improve dyspnea, the ability to walk, and respiratory rate in ambulatory patients with breakthrough dyspnea. The findings of this preliminary study justify a larger randomized, controlled trial for confirmation, said lead author David Hui, MD, Palliative Care and Rehabilitation Medicine, University of Texas MD Anderson Cancer Center, Houston.
“Dyspnea is one of the most common and distressing symptoms in cancer patients, and often worsens with breakthrough episodes on exertion. We hypothesized that subcutaneous fenta- nyl given before exertion could alleviate breakthrough dyspnea,” Hui said.
Twenty ambulatory patients were enrolled in the trial and all stayed on study. They were asked to perform a baseline 6-minute walk test (6MWT), and then were assigned to subcutaneous fentanyl or placebo before taking another 6MWT. The investigators measured change in dyspnea numeric rating scale, walk distance, vital signs, and adverse events between the first and second 6MWTs.
Subcutaneous fentanyl was associated with significant improvements in a dyspnea numeric rating score at the end of the second 6MWT, with a mean change of –1.8 (P = .02). Significant improvements were also seen in dyspnea at rest 15 minutes after drug administration (P = .04), fatigue Borg Scale after the 6MWT (P = .04), 6MWT distance (+37.2 m, P = .03), and respiratory rate (–2.4, P = .03). No adverse events were observed.
Hui noted that there was a large, but nonsignificant, placebo effect in the trial.
Hui D, Xu A, Frisbee-Hume S, et al. Prophylactic subcutaneous fentanyl for exercise-induced breakthrough dyspnea: a preliminary double-blind, randomized controlled trial. Support Care Cancer. 2013;21(suppl 1):S191. Abstract 0542.
High Marks for Nutritional Supplement in Localized Prostate Cancer
A food supplement containing pomegranate seed, green tea, broccoli, and turmeric taken twice a day significantly lowered prostate-specific antigen (PSA) levels compared with placebo in men with localized prostate cancer, according to the results of a double-blind, placebo-controlled clinical trial. Use of the supplement allowed more men to remain on observation alone, without having to resort to salvage surgery, radiation, or androgen-deprivation therapy (ADT).
Called Pomi-T, the supplement is commercially available. Previous animal models and phase 2 studies demonstrated that these polyphenol- rich foods have anticancer effects. The study presented at MASCC 2013 is the first adequately powered, randomized, controlled phase 3 trial of Pomi-T (natureMedical Products) in men with localized prostate cancer. The study was also presented at the 2013 American Society of Clinical Oncology Annual Meeting.
The investigators enrolled 203 men (average age, 74 years) whose PSA was rising after radiotherapy or surgery for localized prostate cancer. They were managed with active surveillance (59%) or watchful waiting (41%), and randomized to receive 2 capsules of Pomi-T per day or placebo for 6 months.
At 6 months of follow-up, median rise in PSA was 14.7% in the Pomi-T group versus 78.5% in the placebo group, representing a 63.8% difference favoring the supplement (P = .0008). PSA levels were stable or lower than baseline in significantly more men in the supplement group: 46% versus 14%, representing a 32% difference (P = .00001).
At follow-up, fewer men taking Pomi-T were assigned to any form of radiation, surgery, or ADT (7.4% vs 26%; P = .01). There were no significant differences between the 2 groups in laboratory measurements of cholesterol, blood pressure, serum glucose, C-reactive protein, or adverse events.
Taking the supplement allowed more men to continue on active surveillance: 92.6% for Pomi-T versus 74% for placebo.
“These results are awesome. We didn’t expect such a big response. This can change practice, because men and their doctors look at their PSA as a deciding factor in whether to continue on active management,” stated lead author Robert Thomas, MD, consulting oncologist at Bedford Hospital and Addenbrooke’s, part of Cambridge University Hospitals, United Kingdom.
Importantly, this supplement is well tolerated and may even improve digestion and urinary symptoms, Thomas said. It is easy for men to stay on therapy with the supplement, and men are more amenable to taking a nutritional supplement than an active drug, especially hormone therapy.
This product does not appear to act on hormones. The investigators plan to study Pomi-T in men with different stages of prostate cancer, as well as those taking ADT.
The study was not funded by the makers of Pomi-T.
Thomas R, Williams M, Bellamy P. A polyphenol rich whole food supplement reduces PSA progression in men with prostate cancer in a double blind placebo controlled RCT—the UK national Pomi-T study. Support Care Cancer. 2013;21(suppl 1):S33. Abstract 0040.
Lymphedema in Head and Neck Cancer
Although little is known about the prevalence of lymphedema in head and neck cancer (HNC), a series of studies found that three-quarters of patients with HNC have problematic lymphedema, both internally and externally.
“Lymphedema is a significant problem affecting a majority of HNC patients. Treatments such as surgery, chemotherapy, radiation, and combined modality therapy can damage lymphatic structures, leading to scar tissue and fibrosis. Lymphedema can be detected noninvasively, and this can inform clinical practice,” stated Sheila Ridner, PhD, RN, FAAN, Vanderbilt University School of Nursing, Nashville, Tennessee.
The studies examined prevalence, symptoms, measurement techniques, and symptom assessment tools. Study 1 included 81 patients at least 3 months out from treatment. After a posttreatment interval of a median of 17.7 months, 75.3% had late-effect lymphedema; of these patients, 9.8% had external lymphedema exclusively, 39.4% had internal edema exclusively, and 50.8% had both types.
Study 2 included 25 patients with HNC. Swelling (both internal and external) was measured before and after treatment at 6 and 12 weeks using digital photography and National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v.4.02. At baseline, digital photography identified external swelling more often than did CTCAE. Internal swelling was identified at baseline in 10 patients, and only 4 had been treated with surgery. Digital photography captured 100% of cases of internal swelling and 92% of cases identified by CTCAE.
Study 3 included 100 patients and followed the time course and patterns of internal and external swelling over 36 weeks. Preliminary findings regarding external lymphedema using 3 different tools (Foldi, CTCAE-lymphedema, CTCAE-fibrosis) showed that by 36 weeks post treatment for HNC, >50% had lymphedema.
Internal lymphedema, as documented via scoping procedures on the Patterson scale, was present in a few structures in 10% to 20% of patients prior to treatment. At 36 weeks post treatment, about 30% of patients had internal lymphedema, and this was observed in more structures than noted prior to treatment.
Study 4 included 30 patients and found that 10 major symptoms were reported by >50% of patients.
Taken together, these studies help characterize the prevalence, patterns, and assessment of lymphedema in HNC. Ridner said that patients should be educated about lymphedema before, during, and after treatment. Internal and external examinations should be conducted to look for lymphedema, and signs and symptoms of lymphedema should be evaluated at each clinic visit.
Patients should be referred to lymphedema treatments when indicated.
Ridner S, Deng J, Murphy BA, et al. Lymphedema in patients with head and neck cancer. Support Care Cancer. 2013;21(suppl 1):S196. Abstract 0558.
Importance of Evaluating Swallowing in Advanced Cancer
A study reported that about 1 in 5 patients with advanced cancer have difficulty swallowing when admitted to the hospital; even at discharge, some still have problems.
Difficulty swallowing is an independent predictor of survival in advanced cancer. These findings highlight the critical need for regular evaluation to ensure adequate nutrition and patient care, according to lead author Shiva Shrotriya, MD, Harry R. Horvitz Center for Palliative Medicine at the Cleveland Clinic Taussig Cancer Institute, Ohio.
The study was based on electronic medical records of 249 patients with solid tumors treated in an acute palliative medical unit from 2008 through 2011. Patients’ ability to swallow was evaluated by a routine swallow screen, preswallow test questionnaires, and a clinical swallow test. The clinical swallow test included a sip of water without aspiration and a 3-ounce cup of water without aspiration.
Mean age was 68 years, 57% were female, 71% were white, 25% were African American, and 4% “other”; 47% had metastatic disease. Mean length of hospital stay was 8 to 10 days. On admission, 6% had difficulty swallowing, and 6% also had difficulty swallowing at discharge; 21% had difficulty swallowing during the hospital stay.
“Most patients who underwent a formal clinical swallow test failed the routine swallow screen, and pneumonia/respiratory and gastrointestinal problems were common among those with difficulty swallowing,” Shrotriya stated.
Shrotriya S, Thomas S, Timmer R, et al. Prevalence and incidence of difficulty swallowing in advanced cancer. Support Care Cancer. 2013;21(suppl 1):S188. Abstract 0535.
Naloxegol for Opioid-Induced Constipation
Two large well-designed studies of patients with opioid-induced constipation (OIC) demonstrated that naloxegol rapidly improved stool frequency and did not compromise opioid-mediated analgesia. In both KODIAC-04 and KODIAC-05, participants were not patients with cancer, and AstraZeneca plans to study naloxegol to establish its safety and efficacy in patients with cancer pain.
“Opioid-induced constipation is a major challenge in palliative care medicine for patients taking opioid analgesics who develop persistent constipation that does not respond to available treatments. Naloxegol holds promise for the treatment of OIC without interfering with opioid analgesia for pain,” said lead author Jan Tack, MD, PhD, Translational Research Center for Gastrointestinal Disorders, University of Leuven, Belgium.
The KODIAC studies are part of a large development program for naloxegol, a peripherally acting mu-opioid–receptor antagonist under investigation for the treatment of patients with OIC.
KODIAC-04 and KODIAC-05 were identically designed, phase 3 randomized, double-blind, placebo-controlled pivotal trials that evaluated 2 daily doses of this novel oral agent: 12.5 mg and 25 mg. In both studies, the 25 mg dose of naloxegol met both primary and secondary end points, but in KODIAC-05, the 12.5 mg dose failed to achieve statistical significance.
KODIAC-04 included 641 patients taking 30 to 1000 morphine equivalents each week for pain who were randomized 1:1:1 to receive placebo or naloxegol 12.5 mg/day or 25 mg/day. Response was defined as having at least 3 spontaneous bowel movements per week, with an increase of at least 1 spontaneous bowel movement over baseline for at least 9 weeks and for at least 3 of the previous 4 weeks. Response rates were 29.4% for placebo, 40.8% for the lower dose (P = .015 vs placebo), and 44.4% for the higher dose (P = .001 vs placebo).
KODIAC-05 included 696 patients similar to the population in KODIAC-04. Response rates were 29.3% for placebo, 34.9% for the 12.5 mg dose, and 39.7% for the 25 mg dose. Only the 25 mg dose was statistically significant compared with placebo (P = .021).
For both trials, median time to first postdose laxation was significantly shorter for both doses of naloxegol compared with placebo (P <.001). No increase in pain scores or need for higher doses of opioids was observed in patients taking naloxegol.
Adverse events (AEs) were more frequent on naloxegol 25 mg and included abdominal pain, diarrhea, nausea and vomiting, and flatulence. Major cardiovascular events were rare and were similar across treatment groups. In KODIAC-04, any AEs were reported in 46.9% of patients receiving placebo, 49.3% of patients taking naloxegol 12.5 mg, and 61.2% of those taking naloxegol 25 mg. In KODIAC-05, any AEs were reported in 58.9%, 59.6%, and 69.0% of patients, respectively. Discontinuations due to AEs were higher in the 25 mg dose groups; in both trials about 5% of patients receiving either placebo or naloxegol 12.5 mg discontinued therapy because of AEs, compared with about 10% of those receiving the higher naloxegol dose. The rates of serious AEs were low in both trials, and occurred more frequently in the placebo and 12.5 mg dose groups than in the 25 mg dose groups.
Tack J, Gralla R, Webster L, et al. Efficacy and safety of naloxegol in patients with opioid-induced constipation (OIC): results from 2 identical phase 3, prospective, randomized, multicenter, double-blind, controlled trials. Support Care Cancer. 2013;21(suppl 1):S260. Abstract 0737.
Managing Oral Mucositis
MuGard has been approved in Europe for the prevention and treatment of oral mucositis (OM). It was found to be safe and effective in alleviating the signs and symptoms of OM in an interim analysis of the first patients enrolled in a randomized controlled clinical trial. The final results will be presented in the future and will be based on 120 patients.
“There is no accepted prophylaxis or therapy for OM—a frequent and debilitating adverse event of concomitant chemoradiotherapy. Saline bicarbonate [SBC] rinse is recommended by the NCI [National Cancer Institute] as a standard for care for HNC [head and neck cancer]. We compared SBC versus MuGard to attenuate OM symptoms,” explained lead author Ron R. Allison, MD, 21st Century Oncology Carolina Radiation Medicine, Greenville, North Carolina.
MuGard is a mucoadhesive oral wound rinse used to manage OM or stomatitis caused by radiotherapy and/or chemotherapy and other types of oral mouth sores. Classified as a medical device, MuGard is a hydrated polymer system (oral hydrogel). When gently distributed within the mouth, the mucoadhesive formulation results in the formation of a protective coating over the oral mucosa. MuGard was previously shown to reduce the incidence and severity of mucositis in patients with HNC undergoing radiation therapy, compared with data from historical control groups.
In the study presented at MASCC 2013, 70 patients were treated with MuGard rinse every 3 hours up to 6 times per day over a period of 6 to 8 weeks versus SBC given on the same schedule. Patients completed the validated Oral Mucositis Daily Questionnaire (OMDQ) reporting mouth and throat soreness and other symptoms. The primary end point compared the efficacy of the 2 identically packaged oral rinses on reducing OM symptoms as determined by the area under the curve (AUC) of mouth and throat soreness as defined by the OMDQ.
The interim analysis showed that treatment with oral MuGard was significantly superior to SBC, with a mean AUC of 58.9 versus 92.1 in the SBC group (P = .041). MuGard was also significantly better than SBC in alleviating other associated symptoms of OM.
Allison RR, Ambrad AA, Arshoun YM, et al. The multi-institutional, randomized, double-blind, placebo-controlled trial to assess the efficacy of MuGard in mitigating oral mucositis (OM) in chemoradiation-treated (CRT) head and neck cancer patients. Support Care Cancer. 2013;21(suppl 1):S211. Abstract 0605.