Multiple cavities with halo sign in a case of invasive pulmonary aspergillosis during therapy for drug-induced hypersensitivity syndrome

A 67-year-old female with rheumatoid arthritis and asthma-chronic obstructive pulmonary disease overlap syndrome was admitted for drug-induced hypersensitivity syndrome (DIHS) caused by salazosulfapyridine. Human herpes virus 6 (HHV-6) variant B was strongly positive on peripheral blood. Multiple cavities with ground grass opacities rapidly emerged predominantly in the upper and middle lobes. She was diagnosed with invasive pulmonary aspergillosis (IPA), and was treated successfully with antifungal agents. Therapeutic systemic corticosteroids, emphysematous change in the lungs, and the worsening of the patient's general condition due to DIHS were considered major contributing factor leading to IPA. HHV-6 reactivation could have an effect on clinical course of IPA. Cavities with halo sign would provide an early clue to IPA in non-neutropenic and immunosuppressive patients

A prospective phase II study of carboplatin and nab-paclitaxel in patients with advanced non-small cell lung cancer and concomitant interstitial lung disease (HOT1302)

Objectives: Patients with concomitant advanced non-small cell lung cancer (NSCLC) and interstitial lung disease (ILD) are excluded from most clinical chemotherapy trials because of the high risk of exacerbating the latter condition. This study prospectively investigated the efficacy and safety of albumin-bound paclitaxel (nab-paclitaxel) in combination with carboplatin in patients with both advanced NSCLC and ILD. Patients and methods: The enrolled patients had treatment-naive, advanced NSCLC with ILD. Patients received 100 mg/m(2) nab-paclitaxel weekly and carboplatin at an area under the concentration-time curve of 6 once every 3 weeks for 4-6 cycles. The primary endpoint was the overall response rate (ORR); secondary endpoints included toxicity, progression-free survival (PFS), and overall survival (OS). Results: Thirty-six patients were enrolled between April 2014 and September 2017. Sixteen patients (44.4%) had adenocarcinoma, 15 (41.7%) had squamous cell carcinoma (Sq), and 5 (13.9%) had non-small cell carcinoma. The median number of cycles administered were 4 (range: 1-6). The ORR was 55.6% (95% confidence interval [CI]: 39.6-70.5). The median PFS and OS were 5.3 months (95% CI: 3.9-8.2) and 15.4 months (95% CI: 9.4-18.7), respectively. A greater proportion of patients with Sq experienced improvements than did those with non-Sq: ORRs, 66.7% (95% CI: 41.7-84.8) vs. 47.6% (95% CI: 28.3-67.6) (P = 0.254); median PFS, 8.2 months (95% CI: 4.0-10.2) vs. 4.1 months (95% CI: 3.3-5.4) (HR, 0.60 [95% CI, 0.30-1.20]; P = 0.15); and median OS, 16.8 months (95% CI: 9.8 not reached) vs. 11.9 months (95% CI: 7.3-17.4) (HR, 0.56 [95% CI, 0.24-1.28]; P = 0.17). Two patients (5.6%) experienced grade >= 2 pneumonitis and 1 patient (2.8%) died. Conclusion: Weekly nab-paclitaxel combined with carboplatin showed favorable efficacy with acceptable toxicity in patients with both advanced NSCLC and ILD

Relationship between dyspnoea and related factors in patients with cancer: a cross-sectional study

令和4年

Rikkunshito for Preventing Chemotherapy-Induced Nausea and Vomiting in Lung Cancer Patients: Results from 2 Prospective, Randomized Phase 2 Trials

The herbal medicine rikkunshito has the potential to improve chemotherapy-induced nausea and vomiting (CINV) by stimulating ghrelin secretion. We aimed to evaluate the efficacy and safety of rikkunshito in preventing CINV for patients with lung cancer. Two separate prospective, randomized, phase II parallel design studies were conducted in patients with lung cancer. Fifty-eight and sixty-two patients scheduled to receive highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC), respectively, were randomized 1:1 to receive either standard antiemetic therapy in accordance with international guidelines (S group) or standard antiemetic therapy plus oral rikkunshito (R group). The primary endpoint was overall complete response (CR)—that is, no emesis and rescue medication in the first 120 h post-chemotherapy. Secondary endpoints included CR in the acute (0–24 h) and delayed (>24–120 h) phases and safety. Fifty-seven patients (S group, 28; R group, 29) receiving HEC and sixty-two patients (S group, 30; R group, 32) receiving MEC with comparable characteristics were evaluated. The CR rates were similar across the S and R groups for the HEC study in the overall (67.9% vs. 62.1%), acute (96.4% vs. 89.6%), and delayed (67.9% vs. 62.1%) phases, respectively, and for the MEC study in the overall (83.3% vs. 84.4%), acute (100% vs. 100%), and delayed (83.3% vs. 84.4%) phases, respectively. No severe adverse events were observed. Although rikkunshito was well tolerated, it did not demonstrate an additional preventative effect against CINV in lung cancer patients receiving HEC or MEC.Clinical Trial Registry Information: This study is registered with the University Hospital Medical Information Network (UMIN) Clinical Trial Registry1, identification numbers UMIN 000014239 and UMIN 000014240

Systemic Opioids for Dyspnea in Cancer Patients: A Real-world Observational Study

Context: Although Systemic opioids are recommended as a pharmacological treatment for cancer-related dyspnea, their effectiveness and safety needs to be investigated in a real-world context. Objectives: To evaluate the effectiveness and safety of systemic regular opioids for dyspnea in cancer patients, in the real-world palliative care practice. Methods: This was a multicenter prospective observational study. We consecutively enrolled adult cancer patients starting regular opioids (morphine, oxycodone, hydromorphone, or fentanyl) for dyspnea from 12 palliative care services across Japan. We evaluated dyspnea intensity using the Numerical Rating Scale (NRS) and Integrated Palliative Outcome Scale (IPOS) every 24 hours until 72 hours after starting opioids (T1–T3). We also evaluated common opioid-related adverse events (AEs) and other severe AEs. Results: We enrolled 402 cancer patients. The proportion of responders was 68.8% (95%confidence intervals (CI): 0.63–0.74) at T1, 75.7% (95%CI: 0.70–0.81) at T2, and 82.1% (95%CI: 0.76–0.87) at T3. The mean differences in dyspnea NRS from baseline were 1.73 (95%CI: 1.46–1.99) at T1, 1.99 (95%CI: 1.71–2.28) at T2, and 2.47 (95%CI:2.13–2.82) at T3. The most common treatment-emergent AE was somnolence with an incidence of the severe form of approximately 10% throughout the study period. In the multivariate analysis, baseline dyspnea NRS ≥6 had a positive correlation with dyspnea relief by systemic regular opioids, while liver metastasis, clinician-predicted survival days, and opioid tolerance had a negative correlation. Conclusion: Regular systemic opioids were effective for dyspnea in real-world cancer patients

The feasibility and effects of a pharmacological treatment algorithm for cancer patients with terminal dyspnea: A multicenter cohort study

Abstract Background How clinicians treat patients with terminal dyspnea widely varies, which could hamper quality care. We visualized comprehensive pharmacological treatment delivered by palliative care physicians. Aim To examine adherence to a comprehensive pharmacological treatment algorithm for patients with terminal dyspnea, and to explore its outcomes during 48 h. Design A multicenter cohort study at five sites (February 2020 to June 2021). Setting/Participants We prospectively enrolled consecutive patients with advanced cancer, Eastern Cooperative Oncology Group performance status 3–4, and moderate/severe dyspnea. Participating palliative care physicians initiated algorithm‐based treatment. The primary outcome was the proportion of adherence to the treatment algorithm over 24 h (predefined goal, 70%). We evaluated the adherence, goal achievement, and dyspnea level with a numerical rating scale (NRS), as well as adverse events over 48 h. Results All 108 patients received algorithm‐based pharmacological treatment. Among 96 and 87 patients who were alive at 24 and 48 h, respectively, 96 (100%; 95% confidence interval [CI] = 96%–100%) and 82 (94%; 95%CI = 87%–98%) continued to receive the algorithm treatment, respectively, and 66 (69%; 95%CI = 59%–77%) and 64 (74%; 95%CI = 63%–82%) achieved the treatment goals, respectively. Using a complete case analysis with paired t‐tests, mean dyspnea NRS scores significantly reduced from 7.3 (standard error, 0.2) at the baseline to 4.9 (0.3) at 24 h (n = 72; p < 0.001), and 7.2 (0.3) at the baseline to 4.6 (0.4) at 48 h (n = 55; p < 0.001). Most adverse events were mild to moderate. Conclusions The comprehensive pharmacological treatment algorithm was feasible, and the study data supports its preliminary efficacy and safety. The use of this algorithm may help clinicians improve care for patients with terminal dyspnea

Case Report : Hereditary Fibrosing Poikiloderma With Tendon Contractures, Myopathy, and Pulmonary Fibrosis (POIKTMP) Presenting With Liver Cirrhosis and Steroid-Responsive Interstitial Pneumonia

Background: Hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis (POIKTMP) is an extremely rare disease caused by mutations in FAM111B, and only approximately 30 cases have been reported worldwide. Some patients develop interstitial pneumonia, which may lead to progressive pulmonary fibrosis and poor prognosis. However, no effective treatment for interstitial pneumonia associated with POIKTMP has been reported. Here, we report an autopsy case of POIKTMP, wherein interstitial pneumonia was improved by corticosteroids.Case Presentation: A 44-year-old Japanese man was referred to our hospital due to poikiloderma, hypotrichosis, and interstitial pneumonia. He developed progressive poikiloderma and muscle weakness since infancy. He also had tendon contractures, short stature, liver cirrhosis, and interstitial pneumonia. Mutation analysis of FAM111B revealed a novel and de novo heterozygous missense mutation, c.1886T > G (p(Phe629Cys)), through which we were able to diagnose the patient with POIKTMP. 3 years after the POIKTMP diagnosis, interstitial pneumonia had worsened. After 2 weeks of administrating 40 mg/day of prednisolone, his symptoms and lung shadows improved. However, he subsequently developed severe hepatic encephalopathy and eventually died of respiratory failure due to bacterial pneumonia and pulmonary edema. Autopsy revealed an unclassifiable pattern of interstitial pneumonia, as well as the presence of fibrosis and fatty degeneration in several organs, including the liver, kidney, skeletal muscle, heart, pancreas, and thyroid.Conclusions: We report a case of POIKTMP in which interstitial pneumonia was improved by corticosteroids, suggesting that corticosteroids could be an option for the treatment of interstitial pneumonia associated with this disease