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%e45% (high dose) or 15%e25% (low dose) of the total daily opioid dose. The primary outcome was change in modified dyspnea Borg scale (0e10) 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 ¼ 13) resulted in significantly lower dyspnea (mean change À1.42; 95% CI À2.37, À0.48; P ¼ 0.007) and greater walk distance (mean change 44 m; P ¼ 0.001) compared to baseline. Low-dose FSS (n ¼ 17) resulted in a nonsignificant reduction in dyspnea (mean change À0.47; 95% CI À1.26, 0.32; P ¼ 0.24) and significant increase in walk distance (mean change 24 m; P ¼ 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 ¼ 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.

Background. Exertional dyspnea is common in patients with cancer and limits their function. The impact of high-flow nasal cannula on exertional dyspnea in nonhypoxemic patients is unclear. In this double-blind, parallel-group, randomized trial, we assessed the effect of flow rate (high vs. low) and gas (oxygen vs. air) on exertional dyspnea in nonhypoxemic patients with cancer. Patients and Methods. Patients with cancer with oxygen saturation >90% at rest and exertion completed incremental and constant work (80% maximal) cycle ergometry while breathing low-flow air at 2 L/minute. They were then randomized to receive high-flow oxygen, high-flow air, low-flow oxygen, or low-flow air while performing symptom-limited endurance cycle ergometry at 80% maximal. The primary outcome was modified 0-10 Borg dyspnea intensity scale at isotime. Secondary outcomes included dyspnea unpleasantness, exercise time, and adverse events.Results. Seventy-four patients were enrolled, and 44 completed the study (mean age 63; 41% female). Compared with low-flow air at baseline, dyspnea intensity was significantly lower at isotime with high-flow oxygen (mean change, −1.1; 95% confidence interval [CI], −2.1, −0.12) and low-flow oxygen (−1.83; 95% CI, −2.7, −0.9), but not high-flow air (−0.2; 95% CI, −0.97, 0.6) or low-flow air (−0.5; 95% CI, −1.3, 0.4). Compared with low-flow air, high-flow oxygen also resulted in significantly longer exercise time (difference + 2.5 minutes, p = .009), but not low-flow oxygen (+0.39 minutes, p = .65) or high-flow air (+0.63 minutes, p = .48). The interventions were well tolerated without significant adverse effects. Conclusion.Our preliminary findings support that high-flow oxygen improved both exertional dyspnea and exercise duration in nonhypoxemic patients with cancer. (ClinicalTrials.gov ID: NCT02357134). The Oncologist 2021;26:e1470-e1479 Implications for Practice: In this four-arm, double-blind, randomized clinical trial examining the role of high-flow nasal cannula on exertional dyspnea in patients with cancer without hypoxemia, high-flow oxygen, but not high-flow air, resulted in significantly lower dyspnea scores and longer exercise time. High-flow oxygen delivered by high-flow nasal cannula devices may improve clinically relevant outcomes even in patients without hypoxemia.

11600 Background: High flow oxygen therapy is effective for hypoxemic respiratory failure. However, its effect on dyspnea in non-hypoxemic patients is unknown. In this 2x2 factorial, double-blind randomized clinical trial, we assessed the effect of flow rate (high vs. low) and gas (oxygen vs. air) on exertional dyspnea in cancer patients. Methods: Non-hypoxemic patients with cancer completed two structured cycle ergometer exercise tests with Low Flow Air [LFAir] at 2 L/min. They were then randomized to receive High Flow Oxygen [HFOx] with up to 60 L/min, High Flow Air [HFAir], Low Flow Oxygen [LFOx] or LFAir during a constant work rate exercise test at 80% maximum. Dyspnea intensity was assessed with the modified 0-10 Borg scale. The primary outcome was difference in the slope of dyspnea intensity vs. time during the third test. Secondary outcomes included difference in exercise time, vital signs, and adverse events. We estimated that 10 patients per arm will provide 86% power to detect a 1-standard deviation main effect and 86% power to detect a 2-SD interaction effect with an alpha of 5%. A linear mixed effects model was used to assess the impact of flow rate and gas on study outcomes. Results: 45 patients were randomized and 44 completed the study (10, 11, 12, 11 patients on HFOx, HFAir, LFOx, LFAir, respectively). The mean age was 63 (range 47-77); 18 (41%) were female; 34 (44%) had lung cancer; and 20 (46%) had metastatic disease. In mixed effects model, the association between the change in dyspnea intensity over time with flow rate differed significantly between oxygen and air (P = 0.04). Specifically, HFOx (slope difference -0.20, P < 0.001) and LFOx (-0.14, P = 0.01) were significantly better than LFAir, but not HFAir (+0.09, P = 0.09). Exercise time also significantly increased with HFOx (difference +2.5 min, P = 0.009) compared to LFAir, but not HFAir (+0.63 min, P = 0.48) or LFOx (+0.39 min, P = 0.65). HFOx was well tolerated without significant adverse effects. Conclusions: The combination of high flow rate and oxygen improved dyspnea and exercise duration during constant work exercise test in non-hypoxemic cancer patients. Larger trials are needed to confirm the benefits of HFOx during exercises. Clinical trial information: NCT02357134.