Opioids impair nivolumab outcomes: a retrospective propensity score analysis in non-small-cell lung cancer.

OBJECTIVES: Opioids are often administered for cancer-related pain relief. However, few reports have evaluated the association between opioids and immune checkpoint inhibitor treatment for patients with non-small-cell lung cancer (NSCLC). The aim of this retrospective study was to reveal the effect of opioids on the prognosis of patients harbouring NSCLC treated with nivolumab. METHODS: The medical records of consecutive patients with NSCLC receiving nivolumab at our institution were retrospectively reviewed. We collected clinical data at the time of nivolumab treatment initiation. Propensity score matching (PSM) was performed to minimise potential selection bias. We compared clinical outcomes with and without baseline opioid use. RESULTS: Of the 296 patients identified in the study, after PSM, 38 cases with opioid use and matched 38 cases without opioid use were selected. The overall response rate was significantly lower in patients with opioid use than in those without (2.63%, 95% CI 0.47% to 13.49%, vs 21.05%, 95% CI 11.07% to 36.35%; p=0.0284). The median progression-free survival in patients with opioid use was significantly shorter than that in patients without (1.17, 95% CI 0.93 to 1.73 months, vs 2.07 95% CI 1.23 to 4.73 months; p=0.002). The median overall survival in patients with opioid use was significantly shorter than that in patients without (4.20, 95% CI 2.53 to 6.20 months, vs 9.57, 95% CI 2.23 to not reached months; p=0.018). CONCLUSIONS: Patients with NSCLC receiving regular opioid administration at nivolumab treatment initiation had a worse nivolumab treatment outcome than patients without opioid use.

Poor effect of osimertinib on EGFR exon 20 insertion-positive lung adenocarcinoma: A case report.

INTRODUCTION: The clinical efficacy of osimertinib for patients with lung adenocarcinoma harboring epidermal growth factor receptor (EGFR) exon 20 insertion mutations is unclear. Few case reports exist on the successful treatment of such tumors with osimertinib. We report a case wherein osimertinib administration had no effect in a patient with EGFR exon 20 insertion-positive lung adenocarcinoma. PATIENT CONCERNS: A 48-year-old never-smoking woman was referred to our hospital for chronic cough. Computed tomography (CT) and positron emission tomography-CT revealed a nodule in the right middle lobe, consolidation in the right upper lobe, multiple lymph node metastases, liver metastasis, and multiple bone metastases. DIAGNOSIS: On the basis of further examination using transbronchial lung biopsy, the patient was diagnosed with cT1N3M1 stage IVB lung adenocarcinoma. An EGFR exon 20 insertion, without any additional mutations, was identified. INTERVENTIONS: Daily oral administration of 80 mg osimertinib was initiated to treat the EGFR exon 20 insertion-positive lung adenocarcinoma. OUTCOMES: Although the disease appeared to be stable 2.5 months after the administration of osimertinib, the tumor started to grow 3 months after administration, and carcinoembryonic antigen levels became higher than those before treatment. Thus, osimertinib was discontinued, and treatment with carboplatin as well as pemetrexed and bevacizumab was started, which the patient responded to. CONCLUSION: EGFR exon 20 insertion mutations must be classified in more detail to assess the efficacy of EGFR tyrosine kinase inhibitors. Osimertinib doses that provide favorable therapeutic windows should be considered. Further clinical research is required to clarify the efficacy of osimertinib and other drugs for exon 20 insertion mutations.

Predictive factors for progression-free survival in non-small cell lung cancer patients receiving nivolumab based on performance status.

BACKGROUND: Nivolumab has promising efficacy for the treatment of non-small cell lung cancer (NSCLC). Various predictive factors for nivolumab response in those with NSCLC have been reported, including performance status (PS). The objective of this retrospective study was to determine the predictive factors for nivolumab response in those with NSCLC with good PS and those with poor PS. METHODS: We retrospectively collected pretreatment clinical data of 296 consecutive patients with NSCLC treated with nivolumab. We investigated the relationship between progression-free survival (PFS) and patient characteristics and analyzed predictive factors associated with good PS (PS 0-1) or poor PS (PS 2-4). RESULTS: The median age of patients was 70 years; 206 patients were male, and 224 were classified as having good PS (PS 0-1). The median PFS was 3.0 months, 3.7 months, and 1.2 months for all patients, patients with good PS, and patients with poor PS respectively. Multivariate analysis showed that never smoking (hazard ratio [HR], 1.77; 95% confidence interval [CI], 1.15-2.75), high C-reactive protein (CRP) (HR, 1.39; 95% CI, 1.00-1.93), liver metastasis (HR, 1.95; 95% CI, 1.24-3.07), pleural effusion (HR, 1.45; 95% CI, 1.06-2.00), and steroid use (HR, 2.85; 95% CI, 1.65-4.94) were associated with significantly shorter PFS in patients with good PS. A high advanced lung cancer inflammation index (ALI) was significantly associated with longer PFS in patients with poor PS (HR, 0.24; 95% CI, 0.08-0.79). CONCLUSIONS: In patients with NSCLC treated with nivolumab, the factors found to be predictive of shorter PFS in patients with good PS were never smoking, high CRP, liver metastasis, pleural effusion, and steroid administration, whereas high ALI was predictive of longer PFS in patients with poor PS.

[Case of renal subcapsular hematoma caused by flexible transurethral lithotripsy].

A 39-year-old man with macroscopic hematuria was admitted to our hospital. A stone, 5 mm in diameter was detected in the right ureteropelvic junction after abdominal computed tomography and plain abdominal radiography. We performed flexible transurethral lithotripsy (f-TUL) and crushed the stone and extracted almost all stone fragments without any complications. However, almost immediately after the operation, the patient began to complain about pain in the right back. In the results of abdominal plain computed tomography right renal subcapsular hematoma was detected. Because active bleeding was not observed in the results of enhanced computed tomography, only conservative treatment was performed. The patient was discharged from the hospital on day 11 of hospitalization. One month after the operation, plain computed tomography was performed and diminished subcapsular hematoma was detected. Renal subcapsular hematoma is assumed to be a unique complication of extracorporeal shock wave lithotripsy. This is the first report of a case of renal subcapsular hematoma caused by f-TUL. The onset of renal subcapsular hematoma following f-TUL could have been caused either because the laser fiber thrust into the renal lithiasis unintentionally or because the internal pressure of the renal pelvis increased substantially during the operation.

Potential of histone deacetylase inhibitors for bladder cancer treatment.

Bladder cancer incidence increases with age, presumably reflecting a cumulative exposure to carcinogens and ever-increasing life expectancy. While aberrant protein expression due to DNA mutations is an essential step during oncogenesis, one recent interest has been the role of epigenetic changes in regulating bladder tumor development. Because aberrant histone acetylation has been linked to malignant diseases in several cases, histone deacetylase inhibitors have great potential as new anticancer drugs owing to their ability to modulate transcription and induce differentiation and apoptosis. We herein review the current knowledge on epigenetic issues in bladder cancer, particularly regarding histone acetylation, and discuss its implications for understanding the molecular basis and treatment of this disease.

[Low-dose docetaxel in combination with dexamethasone for hormone-refractory prostate cancer].

PURPOSE: Efficacy and tolerability of docetaxel-based chemotherapy against hormone-refractory prostate cancer (HRPC) has been shown lately. The objective of this study was to evaluate retrospectively the efficacy and toxicity of low-dose docetaxel in combination with dexamethasone. PATIENTS AND METHODS: Sixteen patients, with a median age of 69.5 years (range 54-85 years), diagnosed with HRPC were administered a treatment regimen consisting of docetaxel (60-80 mg/body or 50 mg/m2) once every 3 or 4 weeks and dexamethasone 1 mg daily at our institution between November, 2004 and March, 2010. RESULTS: The patients received a median of 11.5 cycles of treatment (range, 2-35 cycles). Eleven of 16 patients (68.8%) had a > or = 50% decrease in serum prostate-specific antigen. The median progression-free survival and overall survival times were 7.1 and 20.3 months, respectively. Grade 3 neutropenia occurred only in 2 patients. Infective endocarditis, gastrointestinal or cerebral hemorrhage, and compressive fracture were occurred in each patient. CONCLUSIONS: The combination of low-dose docetaxel every 3-4 weeks and dexamethasone daily was effective and well tolerated in patients with HRPC. However, it is necessary to pay continuous attention to side effects due to the frequent presence of comorbid diseases particularly in the elderly.

Combined chemotherapy with gemcitabine and cisplatin for metastatic urothelial carcinomas in patients 80 years of age and over.

BACKGROUND: This retrospective study aimed to determine the efficacy and toxicity of a combined chemotherapeutic regimen of gemcitabine and cisplatin (GC) for the treatment of metastatic urothelial carcinomas (UCs) in patients 80 years of age and over. PATIENTS AND METHODS: Twelve patients who were at least 80 years old and had been diagnosed with metastatic UC were treated with GC. The patient cohort consisted of 9 men and 3 women, with a median age of 83 (range 80-84) years. The median follow-up was 54 (range 14-80) months. RESULTS: Five out of the 12 patients (42%) showed an objective response, with two achieving a clinically complete response and three a partial response with GC. The median time to progression was 6 months, and the median overall survival was 14 months. The grade 3 and 4 toxicities of the regimen were primarily hematological, including anemia (33%), neutropenia (58%), and thrombocytopenia (50%). No grade 3 or 4 non-hematological toxicities were found. CONCLUSION: GC appears to be an effective and well-tolerated regimen for the treatment of metastatic UCs in very old patients.

Health-related quality of life and treatment outcomes for men with prostate cancer treated by combined external-beam radiotherapy and hormone therapy.

BACKGROUND: Health-related quality of life (HR-QOL) is important when considering the treatment options for prostate cancer. METHODS: From 1992 to 1998, 57 patients were treated by radiotherapy plus hormone therapy (median age, 79 years; median prostate-specific antigen concentration, 15.0 ng/ml; median radiotherapy dosage, 60 Gy). General HR-QOL was measured by the European Organization for Research and Treatment of Cancer Prostate Cancer QOL Questionnaire, and a newly developed disease-specific QOL survey was used to assess urinary and bowel functions. QOL was also measured in a control group of patients admitted for prostate biopsy. RESULTS: The general HR-QOL scores in the radiation group ranged from 70.0 to 91.3, with sexual problems showing the lowest (i.e., worst) score (38.5). Compared with the control group, the scores in the radiation group were worse for physical function and sexual problems. For disease-specific QOL, the radiation group had worse urinary function than controls, but were more satisfied with their urinary function. There was no difference between the radiation group and controls in satisfaction with bowel function. When the control group was subdivided at into two groups: age 75 years or less, and age over 75 years, the QOL score in the radiation group was the same as that in the subgroup aged over 75 years. In subgroups of the radiation patients, according to survey period, there was no difference between the first and last surveys in longitudinal HR-QOL evaluations. The 5- and 10-year overall survival rates were 67.6% and 41.6%, respectively, and the 5- and 10-year cause-specific survival rates were 97.9% and 94.7%. CONCLUSION: The combination of radiotherapy and hormone therapy has a good outcome and patients do not experience poor HR-QOL, except for sexual problems. Moreover, the disease-specific QOL is good, especially for urinary bother.