Levorphanol as a Second Line Opioid in Cancer Patients Presenting to an Outpatient Supportive Care Center: An Open-label Study.

CONTEXT: Levorphanol is a potent opioid agonist and NMDA receptor blocker with minimal drug interactions, and there are few reports of its use in cancer patients. OBJECTIVES: We aimed to determine the frequency of successful opioid rotation (OR) to levorphanol and the median opioid rotation ratio (ORR) from Morphine Equivalent Daily Dose (MEDD). METHODS: This is a prospective, single-group, interventional study. Cancer outpatients requiring an OR and receiving a MEDD of 60-300 mg were rotated to levorphanol using a ratio of 10:1 and assessed daily for 10-day. Successful OR was defined as a 2-point improvement in the Edmonton Symptom Assessment System (ESAS) pain score on day 10 or achieving the personalized pain goal between days 3-10 in patients with uncontrolled pain or resolution of opioid side effects (OSE) in those undergoing OR for OSE alone. The ORR to levorphanol was calculated using net-MEDD (MEDD before OR minus the MEDD of the breakthrough opioid used along with levorphanol after OR). RESULTS: Forty patients underwent OR to levorphanol, and uncontrolled pain 35/40 (87.5%) was the most common indication. The median net-MEDD and levorphanol doses were 95 and 10 mg, respectively, and 33/40 (82.5%) had a successful OR with a median (IQR) ORR of 8.56 (7.5-10). Successful OR was associated with significant improvement in ESAS and OSE scale scores. There was a strong association between MEDD and levorphanol dose. CONCLUSION: This study provided preliminary data that cancer patients could be successfully rotated to levorphanol using an ORR of 8.5. Levorphanol was associated with improved pain and symptom control and was well- tolerated.

High-Flow Oxygen and High-Flow Air for Dyspnea in Hospitalized Patients with Cancer: A Pilot Crossover Randomized Clinical Trial.

BACKGROUND: The effect of high-flow oxygen (HFOx) and high-flow air (HFAir) on dyspnea in nonhypoxemic patients is not known. We assessed the effect of HFOx, HFAir, low-flow oxygen (LFOx), and low-flow air (LFAir) on dyspnea. SUBJECTS, MATERIALS, AND METHODS: This double-blind, 4×4 crossover clinical trial enrolled hospitalized patients with cancer who were dyspneic at rest and nonhypoxemic (oxygen saturation >90% on room air). Patients were randomized to 10 minutes of HFOx, HFAir, LFOx, and LFAir in different orders. The flow rate was titrated between 20-60 L/minute in the high-flow interventions and 2 L/minute in the low-flow interventions. The primary outcome was dyspnea numeric rating scale (NRS) "now" where 0 = none and 10 = worst. RESULTS: Seventeen patients (mean age 51 years, 58% female) completed 55 interventions in a random order. The absolute change of dyspnea NRS between 0 and 10 minutes was -1.8 (SD 1.7) for HFOx, -1.8 (2.0) for HFAir, -0.5 (0.8) for LFOx, and - 0.6 (1.2) for LFAir. In mixed model analysis, HFOx provided greater dyspnea relief than LFOx (mean difference [95% confidence interval] -0.80 [-1.45, -0.15]; p = .02) and LFAir (-1.24 [-1.90, -0.57]; p < .001). HFAir also provided significantly greater dyspnea relief than LFOx (-0.95 [-1.61, -0.30]; p = .005) and LFAir (-1.39 [-2.05, -0.73]; p < .001). HFOx was well tolerated. Seven (54%) patients who tried all interventions blindly preferred HFOx and four (31%) preferred HFAir. CONCLUSION: We found that HFOx and HFAir provided a rapid and clinically significant reduction of dyspnea at rest in hospitalized nonhypoxemic patients with cancer. Larger studies are needed to confirm these findings (Clinicaltrials.gov: NCT02932332). IMPLICATIONS FOR PRACTICE: This double-blind, 4×4 crossover trial examined the effect of oxygen or air delivered at high- or low-flow rates on dyspnea in hospitalized nonhypoxemic patients with cancer. High-flow oxygen and high-flow air were significantly better at reducing dyspnea than low-flow oxygen/air, supporting a role for palliation beyond oxygenation.

Prophylactic Fentanyl Sublingual Spray for Episodic Exertional Dyspnea in Cancer Patients: A Pilot Double-Blind Randomized Controlled Trial.

CONTEXT: The optimal dose of fentanyl sublingual spray (FSS) for exertional dyspnea has not been determined. OBJECTIVES: We examined the effect of two doses of prophylactic FSS on exertional dyspnea. METHODS: In this parallel, dose-finding, double-blind randomized clinical trial, opioid-tolerant cancer patients completed a shuttle walk test at baseline. Patients completed a second shuttle walk test 10 minutes after a single dose of FSS equivalent to either 35%-45% (high dose) or 15%-25% (low dose) of the total daily opioid dose. The primary outcome was change in modified dyspnea Borg scale (0-10) between the first and second shuttle walk tests. Secondary outcomes included adverse events as well as changes in walk distance, vital signs, and neurocognitive function. RESULTS: Thirty of the 50 enrolled patients completed the study. High-dose FSS (n = 13) resulted in significantly lower dyspnea (mean change -1.42; 95% CI -2.37, -0.48; P = 0.007) and greater walk distance (mean change 44 m; P = 0.001) compared to baseline. Low-dose FSS (n = 17) resulted in a nonsignificant reduction in dyspnea (mean change -0.47; 95% CI -1.26, 0.32; P = 0.24) and significant increase in walk distance (mean change 24 m; P = 0.01) compared to baseline. Global evaluation showed high-dose group was more likely to report at least somewhat better improvement (64% vs. 24%; P = 0.06). No significant adverse events or detriment to vital signs or neurocognitive function was detected. CONCLUSION: Prophylactic FSS was well tolerated and demonstrated a dose-response relationship in improving both dyspnea and walk distance. High-dose FSS should be tested in confirmatory trials.