ABSTRACT
Stem cell transplantation (SCT), an effective therapy for amyloid light chain (AL) amyloidosis patients, is associated with low treatment-related mortality (TRM) with appropriate patient selection and risk-adapted dosing of melphalan (RA-SCT). Consolidation after SCT increases hematologic complete response (CR) rates and may improve overall survival (OS) for patients with Subject(s)
Amyloidosis/drug therapy
, Amyloidosis/mortality
, Melphalan/administration & dosage
, Amyloidosis/therapy
, Bortezomib/therapeutic use
, Consolidation Chemotherapy/methods
, Disease-Free Survival
, Follow-Up Studies
, Humans
, Immunoglobulin Light Chains
, Middle Aged
, Remission Induction
, Retrospective Studies
, Risk Adjustment
, Stem Cell Transplantation
, Survival Rate
Subject(s)
Cord Blood Stem Cell Transplantation , HLA Antigens , Haplotypes , Hematologic Neoplasms , Receptors, KIR , Transplantation Chimera , Adolescent , Adult , Aged , Allografts , Child, Preschool , Female , HLA Antigens/blood , HLA Antigens/genetics , Hematologic Neoplasms/blood , Hematologic Neoplasms/genetics , Hematologic Neoplasms/therapy , Humans , Infant , Male , Middle Aged , Receptors, KIR/blood , Receptors, KIR/genetics , Retrospective Studies , Transplantation Chimera/blood , Transplantation Chimera/geneticsABSTRACT
BACKGROUND: This study evaluated the addition of sorafenib to gemcitabine and cisplatin in biliary adenocarcinoma first-line therapy. METHODS: Patients with advanced biliary adenocarcinomas received gemcitabine 1000 mg m(-2) and cisplatin 25 mg m(-2) on a 2 weeks on/1 week off cycle and sorafenib 400 mg twice daily. After the initial 16 patients were enrolled, the chemotherapy doses were amended in view of grade 3 and 4 hand-foot skin reaction and haematologic toxicity. Subsequently, 21 patients received gemcitabine 800 mg m(-2), cisplatin 20 mg m(-2) and sorafenib 400 mg. The primary end point was an improvement in 6-month progression-free survival (PFS6) from historical 57-77% (90% power, type I error of 10%). Pretreatment pERK, evaluated by immunostaining, was correlated with clinical outcome. RESULTS: A total of 39 patients were accrued. The most common grade 3-4 toxicities noted in >10% of patients were fatigue, elevated liver function tests and haematologic toxicities including thromboemboli, hyponatraemia and hypophosphataemia. Six-month progression-free survival was 51% (95% confidence interval (CI) 34-66%). Median PFS and overall survival were 6.5 (95% CI: 3.5-8.3) and 14.4 months (95% CI: 11.6-19.2 months), respectively. No correlation was observed between pERK and outcomes. CONCLUSION: The addition of sorafenib to gemcitabine and cisplatin in biliary adenocarcinomas did not improve efficacy over historical data, and toxicity was increased.
Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biliary Tract Neoplasms/drug therapy , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Bile Duct Neoplasms/drug therapy , Bile Duct Neoplasms/pathology , Bile Ducts, Extrahepatic/pathology , Bile Ducts, Intrahepatic/pathology , Biliary Tract Neoplasms/pathology , Cholangiocarcinoma/drug therapy , Cholangiocarcinoma/pathology , Cisplatin/administration & dosage , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Disease-Free Survival , Female , Gallbladder Neoplasms/drug therapy , Gallbladder Neoplasms/pathology , Humans , Male , Middle Aged , Niacinamide/administration & dosage , Niacinamide/analogs & derivatives , Phenylurea Compounds/administration & dosage , Sorafenib , Treatment Outcome , GemcitabineABSTRACT
BACKGROUND: The hepatic artery lymph node (HALN) is frequently sampled during pancreaticoduodenectomy (PD). Data suggest that survival in the setting of HALN metastases is similar to that of stage IV pancreatic ductal adenocarcinoma (PDAC). The objectives of this study were to describe the prognostic significance of HALN metastases and to assess the predictive performance of HALN compared to peripancreatic lymph node status. METHODS: Patients undergoing PD for PDAC from January 2000-October 2010 were identified from a prospectively maintained database. Patients were included if during PD the HALN was submitted for pathologic evaluation. Patients were excluded if margins were macroscopically positive, if pathology was found to be consistent with a diagnosis other than PDAC. Overall (OS) and disease-free survival (DFS) were estimated by Kaplan-Meier methods. RESULTS: Of the 671 patients who underwent PD for PDAC, HALN status was analyzed for 147 patients. HALN was positive in 23 patients (16 %), 38 were peripancreatic lymph node (PPLN) and HALN negative, and 86 were PPLN+/HALN-. Median follow-up for survivors was 10 months. In a multivariable model, lymph node status and tumor differentiation predicted OS and DFS. Hazard of death and relapse/death were highest among the HALN+ patients (hazard ratio [HR] 2.94; p = 0.017 and HR 2.66; p = 0.011, respectively). Kaplan-Meier analysis revealed significant differences in OS (p = 0.017) and DFS (p = 0.013) based on lymph node status. CONCLUSIONS: OS and DFS are significantly reduced in patients with a positive HALN. Differentiation and lymph node status were predictors of OS and DFS. In the multivariate models, differentiation and lymph node status remain independent predictors of OS and DFS.