Safety and efficacy of gemcitabine plus docetaxel (GD) and capecitabine plus docetaxel (CD) were compared in patients with metastatic breast cancer, where the alternate crossover monotherapy (GD→C or ...CD→G) was predetermined.
Patients were randomly assigned to 3-week cycles of either gemcitabine 1000 mg/m2 on days 1 and 8 plus docetaxel 75 mg/m2 on day 1 or capecitabine 1000 mg/m2 twice daily on days 1–14 plus docetaxel 75 mg/m2 day 1. Upon progression, patients received crossover monotherapy. Primary end point was time to progression (TtP). Secondary end points evaluated overall response rate (ORR), overall survival (OS), and adverse events (AEs).
Despite over-accrual of 475 patients, the trial matured with only 324 of 385 planned TtP events due to patient discontinuations. Human epidermal growth factor receptor 2 status was not captured in this study. More CD patients (28%) discontinued due to AEs than GD patients (18.0%, P = 0.009). TtP hazard ratio (HR) = 1.101, 95% confidence interval (CI) 0.885–1.370, P = 0.387 and OS (HR = 1.031, 95% CI 0.830–1.280, P = 0.785) were not significantly different comparing GD and CD. ORR was not statistically different (P = 0.239) comparing GD (72 of 207, 34.8%) and CD (78 of 191, 40.8%). TtP, OS, and ORR were not significantly different comparing crossover groups. GD caused greater fatigue, hepatotoxicity, neutropenia, and thrombocytopenia but not febrile neutropenia; CD caused more hand–foot syndrome, gastrointestinal toxicity, and mucositis.
GD and CD produced similar efficacy and toxicity profiles consistent with prior clinical experience.
Background: The randomized, double-blind OlympiA trial compared 1 year of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor, olaparib, to matching placebo as adjuvant therapy for ...patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2-negative, early breast cancer (EBC). The first pre-specified interim analysis (IA) previously demonstrated statistically significant improvement in invasive disease-free survival (IDFS) and distant disease-free survival (DDFS). The olaparib group had fewer deaths than the placebo group, but the difference did not reach statistical significance for overall survival (OS). We now report the pre-specified second IA of OS with updates of IDFS, DDFS, and safety. Patients and methods: One thousand eight hundred and thirty-six patients were randomly assigned to olaparib or placebo following (neo)adjuvant chemotherapy, surgery, and radiation therapy if indicated. Endocrine therapy was given concurrently with study medication for hormone receptor-positive cancers. Statistical significance for OS at this IA required P < 0.015. Results: With a median follow-up of 3.5 years, the second IA of OS demonstrated significant improvement in the olaparib group relative to the placebo group hazard ratio 0.68; 98.5% confidence interval (CI) 0.47-0.97; P = 0.009. Four-year OS was 89.8% in the olaparib group and 86.4% in the placebo group (Delta 3.4%, 95% CI -0.1% to 6.8%). Four-year IDFS for the olaparib group versus placebo group was 82.7% versus 75.4% (Delta 7.3%, 95% CI 3.0% to 11.5%) and 4-year DDFS was 86.5% versus 79.1% (Delta 7.4%, 95% CI 3.6% to 11.3%), respectively. Subset analyses for OS, IDFS, and DDFS demonstrated benefit across major subgroups. No new safety signals were identified including no new cases of acute myeloid leukemia or myelodysplastic syndrome. Conclusion: With 35 years of median follow-up, OlympiA demonstrates statistically significant improvement in OS with adjuvant olaparib compared with placebo for gBRCA1/2pv-associated EBC and maintained improvements in the previously reported, statistically significant endpoints of IDES and DDFS with no new safety signals.
Exemestane is an aromatase inactivator. 769 Postmenopausal women with advanced breast cancer who had failed on tamoxifen were randomised to exemestane or megoestrol acetate in this double-blind ...trial. Objective response rate was similar between treatments. Median time to progression, time to treatment failure and overall survival was significantly longer with exemestane. Drug-related withdrawals and drug-related deaths were more common with megoestrol acetate.
Lung Cancer Immunotherapy Raez, Luis E; Fein, Steven; Podack, Eckhard R
Clinical medicine & research,
11/2005, Letnik:
3, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Recent insights into anti-tumor immunotherapy have led to a wave of clinical trials involving immunotherapy for lung cancer. Vaccines have evolved from nonspecific immune stimulants, like Bacillus ...Calmette-Guerin (BCG), to much more specific and potent strategies, some of which generate active immune responses against tumor-associated antigens. Understanding the mechanisms of anti-tumor immunity and identifying target antigens will likely improve these therapeutic strategies and provide them with a niche in the future of lung cancer therapy.
Background
Long-term complications after laparoscopic gastric banding (LAGB) are frequent, leading to reoperations for a substantial number of patients. It is not known whether esophageal motility or ...the lower esophageal sphincter (LES) play a role in the development of complications. The results of preoperative upper gastrointestinal (GI) testing were compared with outcome after LAGB.
Methods
Before LAGB, 68 bariatric patients had esophageal manometry, endoscopy, and pH monitoring. For 61 of these patients (90% follow-up rate), the differences in weight loss, complications, and reoperation rate were retrospectively compared.
Results
Of these patients, 8.2% had a nonspecific motility disorder of the esophagus, 44.3% had an incompetent sphincter shown by manometry, and 17.5% had acid reflux shown by pH monitoring. Endoscopic evaluation showed esophagitis in 10.3% and hiatal hernia in 33.8% of the patients. Abnormal pH monitoring and endoscopic findings were not predictive for the long-term outcome or complications. The presence of an incompetent LES led to reoperation for a greater number of patients (44.4 vs. 14.7%;
p
= 0.01), especially if the band was placed using the pars flaccida technique.
Conclusions
Endoscopy and pH monitoring do not predict outcome for gastric banding and therefore have no relevance in the selection of patients for gastric banding. Patients with an incompetent LES shown by manometry had a higher reoperation rate. If this finding can be confirmed, patients with LES incompetence may need another intervention.
Analogous to the precession of a Foucault pendulum observed on the rotating Earth, a precessing spin observed in a rotating frame of reference appears frequency-shifted. This can be understood as ...arising from a magnetic pseudo-field in the rotating frame that nevertheless has physically significant consequences, such as the Barnett effect. To detect these pseudo-fields, a rotating-frame sensor is required. Here we use quantum sensors, nitrogen-vacancy (NV) centres, in a rapidly rotating diamond to detect pseudo-fields in the rotating frame. Whereas conventional magnetic fields induce precession at a rate proportional to the gyromagnetic ratio, rotation shifts the precession of all spins equally, and thus primarily affect 13 C nuclear spins in the sample. We are thus able to explore these effects via quantum sensing in a rapidly rotating frame, and define a new approach to quantum control using rotationally induced nuclear spin-selective magnetic fields. This work provides an integral step towards realizing precision rotation sensing and quantum spin gyroscopes.
Neutrophils, the most abundant type of leukocytes in blood, can form neutrophil extracellular traps (NETs). These are pathogen-trapping structures generated by expulsion of the neutrophil's DNA with ...associated proteolytic enzymes. NETs produced by infection can promote cancer metastasis. We show that metastatic breast cancer cells can induce neutrophils to form metastasis-supporting NETs in the absence of infection. Using intravital imaging, we observed NET-like structures around metastatic 4T1 cancer cells that had reached the lungs of mice. We also found NETs in clinical samples of triple-negative human breast cancer. The formation of NETs stimulated the invasion and migration of breast cancer cells in vitro. Inhibiting NET formation or digesting NETs with deoxyribonuclease I (DNase I) blocked these processes. Treatment with NET-digesting, DNase I-coated nanoparticles markedly reduced lung metastases in mice. Our data suggest that induction of NETs by cancer cells is a previously unidentified metastasis-promoting tumor-host interaction and a potential therapeutic target.
The efficacy and safety of treatment with cabozantinib in combination with nivolumab and ipilimumab in patients with previously untreated advanced renal-cell carcinoma are unknown.
In this phase 3, ...double-blind trial, we enrolled patients with advanced clear-cell renal-cell carcinoma who had not previously received treatment and had intermediate or poor prognostic risk according to the International Metastatic Renal-Cell Carcinoma Database Consortium categories. Patients were randomly assigned to receive 40 mg of cabozantinib daily in addition to nivolumab and ipilimumab (experimental group) or matched placebo in addition to nivolumab and ipilimumab (control group). Nivolumab (3 mg per kilogram of body weight) and ipilimumab (1 mg per kilogram) were administered once every 3 weeks for four cycles. Patients then received nivolumab maintenance therapy (480 mg once every 4 weeks) for up to 2 years. The primary end point was progression-free survival, as determined by blinded independent review according to Response Evaluation Criteria in Solid Tumors, version 1.1, and was assessed in the first 550 patients who had undergone randomization. The secondary end point was overall survival, assessed in all patients who had undergone randomization.
Overall, 855 patients underwent randomization: 428 were assigned to the experimental group and 427 to the control group. Among the first 550 patients who had undergone randomization (276 in the experimental group and 274 in the control group), the probability of progression-free survival at 12 months was 0.57 in the experimental group and 0.49 in the control group (hazard ratio for disease progression or death, 0.73; 95% confidence interval, 0.57 to 0.94; P = 0.01); 43% of the patients in the experimental group and 36% in the control group had a response. Grade 3 or 4 adverse events occurred in 79% of the patients in the experimental group and in 56% in the control group. Follow-up for overall survival is ongoing.
Among patients with previously untreated, advanced renal-cell carcinoma who had intermediate or poor prognostic risk, treatment with cabozantinib plus nivolumab and ipilimumab resulted in significantly longer progression-free survival than treatment with nivolumab and ipilimumab alone. Grade 3 or 4 adverse events were more common in the experimental group than in the control group. (Funded by Exelixis; COSMIC-313 ClinicalTrials.gov number, NCT03937219.).
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