PURPOSE Adjuvant chemotherapy after D2 gastrectomy is standard for resectable locally advanced gastric cancer (LAGC) in Asia. Based on positive findings for perioperative chemotherapy in European phase III studies, the phase III PRODIGY study (ClinicalTrials.gov identifier: NCT01515748 ) investigated whether neoadjuvant docetaxel, oxaliplatin, and S-1 (DOS) followed by surgery and adjuvant S-1 could improve outcomes versus standard treatment in Korean patients with resectable LAGC. PATIENTS AND METHODS Patients 20-75 years of age, with Eastern Cooperative Oncology Group performance status 0-1, and with histologically confirmed primary gastric or gastroesophageal junction adenocarcinoma (clinical TNM staging: T2-3N+ or T4Nany) were randomly assigned to D2 surgery followed by adjuvant S-1 (40-60 mg orally twice a day, days 1-28 q6w for eight cycles; SC group) or neoadjuvant DOS (docetaxel 50 mg/m2, oxaliplatin 100 mg/m2 intravenously day 1, S-1 40 mg/m2 orally twice a day, days 1-14 q3w for three cycles) before D2 surgery, followed by adjuvant S-1 (CSC group). The primary objective was progression-free survival (PFS) with CSC versus SC. Two sensitivity analyses were performed: intent-to-treat and landmark PFS analysis. RESULTS Between January 18, 2012, and January 2, 2017, 266 patients were randomly assigned to CSC and 264 to SC at 18 Korean study sites; 238 and 246 patients, respectively, were treated (full analysis set). Follow-up was ongoing in 176 patients at data cutoff (January 21, 2019; median follow-up 38.6 months [interquartile range, 23.5-62.1]). CSC improved PFS versus SC (adjusted hazard ratio, 0.70; 95% CI, 0.52 to 0.95; stratified log-rank P = .023). Sensitivity analyses confirmed these findings. Treatments were well tolerated. Two grade 5 adverse events (febrile neutropenia and dyspnea) occurred during neoadjuvant treatment. CONCLUSION PRODIGY showed that neoadjuvant DOS chemotherapy, as part of perioperative chemotherapy, is effective and tolerable in Korean patients with LAGC.
Our study found that pseudoprogression was not frequently observed in NSCLC. Conventional RECIST v1.1 might underestimate the benefit of immune-checkpoint inhibitors. Given the small number of patients studied, further study is warranted on whether treatment with immune-checkpoint inhibitors beyond RECIST progression benefits patients with advanced NSCLC.
PurposeThe pattern of double primary cancers after treatment for gastric cancer is important for a patient's survival.Materials and MethodsWe analyzed the clinicopathologic data of 214 gastric cancer patients from October 1996 to November 2007 with regard to metachronous second primary cancers.ResultsOut of 5,778 patients with gastric cancer, metachronous second primary cancers occurred in 214 patients. The median age was 61.8 years, the number of male and female patients was 140 (65.4%), 74 (34.6%), respectively. The median time to the occurrence of second cancers after diagnosis of the first was 39.2 months (standard deviation, 31.2 months). The most common cancer was colorectal cancer, which occurred in 44 patients (20.6%), and lung cancer in 33 patients (15.4%), hepatocellular carcinoma in 26 patients (12.1%), ovarian cancer in 15 patients (7.0%), cervical cancer in 12 patients (7.0%), breast cancer in 11 patients (5.1%), and esophageal cancer in 11 patients (5.1%). The observed/expected (O/E) ratio showed a significant increase in colorectal (1.25), male biliary (1.60), ovarian (8.72), and cervical cancer (3.33) with primary gastric cancer. After five years from diagnosis of gastric cancer, secondary cancer occurred in 50 patients (23.4%), and breast cancer, prostate cancer, laryngeal cancer, lung cancer, and hepatocellular carcinoma were the most frequent.ConclusionThe O/E ratio showed a significant increase in colorectal, male biliary, ovarian, and cervical cancer with primary gastric cancer, and second primary cancer as the main cause of death for these patients. A follow-up examination for metachronous double primary cancer is needed in order to improve the survival time in patients with gastric cancer.
Adefovir dipivoxil (ADV) is a nucleotide used as long-term therapy of chronic hepatitis B. Many published reports have shown that long-term high-dose therapy with adefovir can be associated with proximal renal tubular dysfunction resulting in significant hypophosphatemia, renal insufficiency and osteomalacia. We have encountered two patients who developed evidence of hypophosphatemic osteomalacia while on long-term low-dose adefovir therapy for chronic hepatitis B. We report on its clinical features and its potential resolution with cessation of the drug and supplementation with phosphate. We also reviewed the other published cases associated with hypophosphatemic osteomalacia after low-dose adefovir therapy. The symptoms and the hypophosphatemia improved after cessation of the drug and supplementation with phosphate in most cases. Patients taking adefovir long-term should receive regular investigation of the phosphate level and renal function.
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