ABSTRACT
Purpose@#This study aimed to evaluate the clinical outcomes and toxicities of salvage proton beam therapy (PBT) in patients with locoregional recurrent non-small cell lung cancer (NSCLC). @*Materials and Methods@#We retrospectively reviewed 53 patients who received salvage PBT for locoregionally recurrent NSCLC between January 2016 and December 2019. The median clinical target volume (CTV) was 71.2 cm3 (range, 13.3 to 1,200.7 cm3). The median prescribed dose was 64.0 cobalt gray equivalent (CGE) (range, 45.0 to 70.0 CGE). One-third of the patients (32.1%) received concurrent chemoradiotherapy (CCRT). @*Results@#The patients’ median age was 67 years (range, 44 to 86 years). The initial treatments were surgery in 31 (58.5%), definitive CCRT in 12 (22.6%), and definitive radiotherapy in 10 (18.9%) patients. The median disease-free interval (DFI) was 14 months (range, 3 to 112 months). Thirty-seven patients (69.8%) had a previous radiotherapy history. Among them, 18 patients (48.7%) had in-field recurrence. The median follow-up time after salvage PBT was 15.0 months (range, 3.5 to 49.3 months). During the follow-up period, 26 patients (49.1%) experienced disease progression: local in 13 (24.5%), regional in 14 (26.5%), and distant metastases in 15 (26.5%). The 2-year overall survival (OS) rate, local control rate, and progression-free survival rate were 79.2%, 68.2%, and 37.1%, respectively. Shorter DFI (≤12 months; p = 0.015) and larger CTV (>80 mL; p = 0.014) were associated with poor OS. Grade 3 toxicities occurred in 8 patients (15.1%): esophagitis in 2, dermatitis in 3, and pulmonary toxicities in 4. @*Conclusion@#Salvage PBT for locoregionally recurrent NSCLC was effective, and treatment-related toxicities were tolerable.
ABSTRACT
Purpose@#This study aimed to evaluate the clinical outcomes and toxicities of salvage proton beam therapy (PBT) in patients with locoregional recurrent non-small cell lung cancer (NSCLC). @*Materials and Methods@#We retrospectively reviewed 53 patients who received salvage PBT for locoregionally recurrent NSCLC between January 2016 and December 2019. The median clinical target volume (CTV) was 71.2 cm3 (range, 13.3 to 1,200.7 cm3). The median prescribed dose was 64.0 cobalt gray equivalent (CGE) (range, 45.0 to 70.0 CGE). One-third of the patients (32.1%) received concurrent chemoradiotherapy (CCRT). @*Results@#The patients’ median age was 67 years (range, 44 to 86 years). The initial treatments were surgery in 31 (58.5%), definitive CCRT in 12 (22.6%), and definitive radiotherapy in 10 (18.9%) patients. The median disease-free interval (DFI) was 14 months (range, 3 to 112 months). Thirty-seven patients (69.8%) had a previous radiotherapy history. Among them, 18 patients (48.7%) had in-field recurrence. The median follow-up time after salvage PBT was 15.0 months (range, 3.5 to 49.3 months). During the follow-up period, 26 patients (49.1%) experienced disease progression: local in 13 (24.5%), regional in 14 (26.5%), and distant metastases in 15 (26.5%). The 2-year overall survival (OS) rate, local control rate, and progression-free survival rate were 79.2%, 68.2%, and 37.1%, respectively. Shorter DFI (≤12 months; p = 0.015) and larger CTV (>80 mL; p = 0.014) were associated with poor OS. Grade 3 toxicities occurred in 8 patients (15.1%): esophagitis in 2, dermatitis in 3, and pulmonary toxicities in 4. @*Conclusion@#Salvage PBT for locoregionally recurrent NSCLC was effective, and treatment-related toxicities were tolerable.
ABSTRACT
Tofacitinib is an oral disease-modifying anti-rheumatic drug to selectively inhibit Janus kinases. Tofacitinib is a representative small molecule inhibitor that is used to treat many diseases including rheumatoid arthritis and various autoimmune conditions.Unlike biological agents, tofacitinib has several advantages, including the ability to be administered orally and a short half-life. This study aimed to evaluate the bioequivalence of the pharmacokinetics (PK) between tofacitinib aspartate 7.13 mg (test formulation) and tofacitinib citrate 8.08 mg (reference formulation; Xeljanz ® ) in healthy subjects. A randomized, open-label, single-dose, 2-sequence, 2-period, 2-treatment crossover trial was conducted in 41 healthy volunteers. A total of 5 mg of tofacitinib as the test or the reference formulation was administered, and serial blood samples were collected up to 14 hours after dosing for PK analyses. The plasma concentration of tofacitinib was determined by ultraperformance liquid chromatography-tandem mass spectrometry. A non-compartmental analysis was used to estimate the PK parameters. A total of 35 subjects completed the study and the study drug was well-tolerated. The mean maximum concentration (Cmax ) and area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast ) for the test formulation were 52.67 ng/mL and 133.86 ng·h/mL, respectively, and 50.61 ng/mL and 133.49 h·ng/mL for the reference formulation, respectively. The geometric mean ratios (90% confidence intervals) of the Cmax and AUClast between the 2 formulations were 1.041 (0.944–1.148) and 1.003 (0.968–1.039), respectively. Tofacitinib aspartate exhibited bioequivalent PK profiles to those of the reference formulation.Trial Registration: ClinicalTrials.gov Identifier: NCT04278391
ABSTRACT
Tofacitinib is an oral disease-modifying anti-rheumatic drug to selectively inhibit Janus kinases. Tofacitinib is a representative small molecule inhibitor that is used to treat many diseases including rheumatoid arthritis and various autoimmune conditions.Unlike biological agents, tofacitinib has several advantages, including the ability to be administered orally and a short half-life. This study aimed to evaluate the bioequivalence of the pharmacokinetics (PK) between tofacitinib aspartate 7.13 mg (test formulation) and tofacitinib citrate 8.08 mg (reference formulation; Xeljanz ® ) in healthy subjects. A randomized, open-label, single-dose, 2-sequence, 2-period, 2-treatment crossover trial was conducted in 41 healthy volunteers. A total of 5 mg of tofacitinib as the test or the reference formulation was administered, and serial blood samples were collected up to 14 hours after dosing for PK analyses. The plasma concentration of tofacitinib was determined by ultraperformance liquid chromatography-tandem mass spectrometry. A non-compartmental analysis was used to estimate the PK parameters. A total of 35 subjects completed the study and the study drug was well-tolerated. The mean maximum concentration (Cmax ) and area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast ) for the test formulation were 52.67 ng/mL and 133.86 ng·h/mL, respectively, and 50.61 ng/mL and 133.49 h·ng/mL for the reference formulation, respectively. The geometric mean ratios (90% confidence intervals) of the Cmax and AUClast between the 2 formulations were 1.041 (0.944–1.148) and 1.003 (0.968–1.039), respectively. Tofacitinib aspartate exhibited bioequivalent PK profiles to those of the reference formulation.Trial Registration: ClinicalTrials.gov Identifier: NCT04278391
ABSTRACT
BACKGROUND: Sevoflurane is an inhalational anesthetic that produces rapid induction, emergence and little cardiovascular depression. Elevated sympathetic activity during surgery produces undesirable effects on the cardiovascular system, such as hypertension, tachycardia or arrhythmias. So combined general and epidural anesthesia have been used recently for the operation, especially the abdominal surgery. This study was performed to evaluate the cardiovascular effects of thoracic epidural anesthesia during sevoflurane general anesthesia. METHODS: Forty patients of ASA class 1-2 undergoing elective subtotal gastrectomy were divided into 5 groups. Thoracic epidural bolus injection was administered via an epidural catheter during sevoflurane general anesthesia in a double-blind random manner: Group 1; normal saline (N/S) 10 ml (placebo), Group 2; morphine 0.1 mg/kg mixed with N/S in 10 ml, Group 3; fentanyl 1 mcg/kg mixed with N/S in 10 ml, Group 4; 1% lidocaine 10 ml, and Group 5; 1% lidocaine 10 ml mixed with morphine 0.1 mg/kg and fentanyl 1 mcg/kg. Systolic and diastolic blood pressures, pulse rates, peripheral oxygen saturation levels (SpO2) and end-tidal carbon dioxide partial pressures (ETCO2) were measured every 5 minutes. RESULTS: Systolic and diastolic blood pressures were significantly reduced from 10 minutes after epidural bolus injection in groups 4 and 5, but these decreases in blood pressure were not severe enough to require treatment in either group. Pulse rates were significantly decreased from 10 minutes after injection in groups 3, 4, and 5, but these decreases in pulse rate were not so severe enough to require treatment in 3 groups. SpO2 and ETCO2 were stable, and arrhythmia was not observed. CONCLUSIONS: The thoracic epidural injection of 1% lidocaine mixed with morphine 0.1 mg/kg and fentanyl 1 mcg/kg can be safely used during sevoflurane anesthesia without severe cardiovascular complications during upper abdominal surgery in ASA 1-2 patients.