ABSTRACT
OBJECTIVE: Sorafenib is the standard of care for patients with advanced hepatocellular carcinoma (HCC), but data on its use in the elderly are inconclusive. METHODS: All consecutive HCC patients who were treated in our institution with sorafenib since its licensing were included in the analysis. Patients were divided into two groups: (A) up to 75 and (B) older than 75 years old. Our endpoints were overall survival (OS) and time to treatment failure (TTF) because of disease progression or toxicity. Safety parameters and the prognostic effect of HCC characteristics were also investigated. RESULTS: Data from 190 patients (157 men), median age 66 (26-87) years, were studied (A=151 and B=39). No significant difference in OS and TTF was detected between the two groups [7.1 (5.5-8.7) vs. 10.4 (6.5-14.3) months, P=0.360 and 4.2 (2.3-6.2) vs. 5.6 (3.1-8.1) months, P=0.369, respectively]. Incidence of toxicities at all grades and dose reductions were comparable between groups A and B. In a multivariate setting, patients with Child-Pugh B score at baseline were associated with a higher risk of death (adjusted hazard ratio=2.17, 95% confidence interval:1.24-3.79, P=0.007) and treatment failure (adjusted hazard ratio=4.64, 95% confidence interval: 2.55-8.42, P=0.001) and had shorter OS and TTF compared with patients with a Child-Pugh A (P=0.004 and P<0.001, respectively). CONCLUSION: Elderly patients with advanced HCC, when treated with sorafenib, have an equivalent clinical outcome with similar toxicity rates as their younger counterparts. Age alone should not be a discriminating factor for the management of advanced HCC with sorafenib.
Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/drug therapy , Niacinamide/analogs & derivatives , Phenylurea Compounds/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Adult , Age Factors , Aged , Aged, 80 and over , Antineoplastic Agents/adverse effects , Carcinoma, Hepatocellular/enzymology , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Chi-Square Distribution , Disease Progression , Humans , Kaplan-Meier Estimate , Liver Neoplasms/enzymology , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Logistic Models , London , Male , Middle Aged , Multivariate Analysis , Niacinamide/adverse effects , Niacinamide/therapeutic use , Odds Ratio , Patient Selection , Phenylurea Compounds/adverse effects , Proportional Hazards Models , Protein Kinase Inhibitors/adverse effects , Retrospective Studies , Risk Factors , Sorafenib , Time Factors , Treatment OutcomeABSTRACT
In the last decade treatment for colorectal cancer (CRC) has evolved with the addition of contemporary chemotherapy drugs and targeted therapies. Despite this progress, our drug armamentarium is by no means complete and modern molecular biology techniques have led to the identification of a number of 'druggable' targets. One of the most important current drug targets is the phosphatidyl-inositol 3-kinase (PI3K) pathway, which is frequently deregulated in patients with CRC. In vitro and in vivo data strongly support the clinical development of compounds affecting signal transduction via the PI3K pathway. In this review we outline the role of PI3K in the development and progression of CRC and discuss data from current and ongoing clinical trials targeting this pathway. In addition we make suggestions toward the optimization of future research in order to derive the maximum benefit for patients with CRC.
Subject(s)
Colorectal Neoplasms/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Signal Transduction , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cell Transformation, Neoplastic/genetics , Cell Transformation, Neoplastic/metabolism , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Humans , Mitogen-Activated Protein Kinases/antagonists & inhibitors , Mitogen-Activated Protein Kinases/metabolism , Molecular Targeted Therapy , Neoplasm Staging , Phosphatidylinositol 3-Kinases/genetics , Phosphoinositide-3 Kinase Inhibitors , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Signal Transduction/drug effectsABSTRACT
Treatment of metastatic and locally advanced pancreatic cancer has made slow progress during the last decade. Single agent gemcitabine or in combination with capecitabine or erlotinib remained the preferred systemic treatment options until 2010 when the ACCORD study demonstrated significantly improved outcomes achieved with FOFIRINOX compared with gemcitabine monotherapy. Since 2010, use of FOLFIRINOX has increased both in metastatic and locally advanced cancer. Despite its gaining popularity among oncologists, unanswered questions remain. Do the often necessary dose modifications affect its efficacy? Are the toxicities manageable and how applicable are the results of the ACCORD study in the general population of patients with newly diagnosed pancreatic cancer? In the present manuscript, we review the published literature regarding the use of FOLFIRINOX, the challenges associated with its use and how it will be optimally incorporated into the management of patients with different stages of pancreatic cancer and ultimately, in a more biomarker-driven pathway algorithm.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Pancreatic Neoplasms/drug therapy , Animals , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Biomarkers, Tumor/metabolism , Camptothecin/administration & dosage , Camptothecin/analogs & derivatives , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Deoxycytidine/therapeutic use , Fluorouracil/administration & dosage , Humans , Irinotecan , Leucovorin/administration & dosage , Organoplatinum Compounds/administration & dosage , Oxaliplatin , Pancreatic Neoplasms/pathology , Treatment Outcome , GemcitabineABSTRACT
Pixantrone is a novel anthracycline derivative, manufactured by Cell Therapeutics Incorporated, WA, USA. It was developed with the aim to retain the efficacy of anthracyclines and be less cardiotoxic. Initial safety trials and single-arm, Phase II trials have shown preliminary evidence of anticancer activity and manageable toxicity. These results were validated in multicenter, randomized clinical trials where pixantrone was used as single agent or in combination with other cytotoxics. Following the results of PIX301, it is now approved by the EMA for use as monotherapy in pretreated patients with refractory non-Hodgkin lymphomas. Ongoing trials are assessing the use of pixantrone in combination with other drugs.