Subject(s)
Janus Kinase 2/genetics , Myocardial Ischemia/etiology , Thrombocythemia, Essential/genetics , Bone Marrow/pathology , Fatal Outcome , Humans , Male , Middle Aged , Mutation , Myocardial Ischemia/pathology , Myocardium/pathology , Shock, Cardiogenic/etiology , Thrombocythemia, Essential/complications , Thrombocythemia, Essential/pathologyABSTRACT
BACKGROUND: The expression of platelet-derived growth factor, a potent mitogen, and its receptor both in tissue and serum correlate with the severity of liver cirrhosis. Over-expression of platelet-derived growth factor has been demonstrated in human hepatocellular carcinoma (HCC) tumors and cell lines. Imatinib, a potent inhibitor of BCR-ABL and c-kit, also inhibits the platelet-derived growth factor receptor tyrosine kinase. The trial was designed to assess the efficacy and safety of imatinib in patients with unresectable HCC. METHODS: Eligibility criteria consisted of HCC patient over the age of 18 with reasonable organ function, unresectable but measurable disease, not candidates for chemoinfusion, and a performance status of 0 to 2. Imatinib was started at 300 mg/d orally with 100 mg/wk dose escalation up to 800 mg/d if toxicity permitted. RESULTS: Fifteen patients, median age 58 years, were enrolled and treated with imatinib. Most, or 7, patients had hepatitis B virus as a risk factor for HCC, followed by hepatitis C virus in 3 patients. Metastatic disease (American Joint Committee on Cancer stage IV) was noted in 13 patients and locally advanced (stage III) in the remainder. The median dose-level of imatinib was 500 mg/d. Two patients had stable disease lasting more than 2 months. The remainder progressed within 2 months of initiation of imatinib. No grade 3 or 4 hematologic toxicity was observed. Two patients had grade 3 elevated liver function tests during treatment; otherwise, there was no other grade 3 or 4 nonhematologic toxicity noted. CONCLUSION: Although toxicities were tolerable, imatinib as a monotherapy for the treatment of unresectable HCC has little, if any, significant efficacy.
Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/drug therapy , Piperazines/therapeutic use , Pyrimidines/therapeutic use , Adult , Aged , Aged, 80 and over , Benzamides , Bone Neoplasms/drug therapy , Bone Neoplasms/secondary , Bone Neoplasms/surgery , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/surgery , Female , Heart Neoplasms/drug therapy , Heart Neoplasms/secondary , Heart Neoplasms/surgery , Humans , Imatinib Mesylate , Liver Neoplasms/secondary , Liver Neoplasms/surgery , Lung Neoplasms/drug therapy , Lung Neoplasms/secondary , Lung Neoplasms/surgery , Male , Middle Aged , Prognosis , Protein-Tyrosine Kinases/antagonists & inhibitors , Survival Rate , Treatment OutcomeABSTRACT
BACKGROUND: The hypervascular nature of hepatocellular carcinoma (HCC) is well characterized. Recent data have suggested that thalidomide possesses antiangiogenic and immunomodulatory activity. Therefore, the authors initiated a study to assess the efficacy and toxicity of thalidomide in patients with advanced HCC as primary and secondary endpoints, respectively. METHODS: Inclusion criteria were unresectable HCC with bidimentionally measurable disease, age > or = 18 years, Eastern Cooperative Oncology Group performance status < or = 2, and adequate organ function. Thalidomide was administered at a starting dose of 200 mg per day in a 100-mg-per-week dose escalation regimen, up to the maximum tolerated dose or to 800 mg per day. Toxicity was monitored according to the National Cancer Institute Common Toxicity Criteria. RESULTS: Twenty-six of 27 patients were eligible and assessable for toxicity and response. A median daily dose of 300 mg was achieved. One patient experienced near-complete recovery of alpha-fetoprotein levels and a partial radiographic response on computed tomography. Two patients had stable disease during the 16-week study period. The median duration of progression-free survival was 42 days. The overall median survival was 123 days. Fatigue and somnolence were the most common side effects, occurring in 81% and 62% of patients, respectively. No Grade 4 hematologic toxicity was observed. Three patients experienced Grade 4 hepatic toxicity (namely, hyperbilirubinemia). CONCLUSIONS: With gradual dose escalation, thalidomide was tolerated in most patients with advanced HCC. However, treatment with thalidomide alone was associated with only a modest response in the treatment of HCC.
Subject(s)
Angiogenesis Inhibitors/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/drug therapy , Thalidomide/therapeutic use , Adult , Aged , Aged, 80 and over , Angiogenesis Inhibitors/adverse effects , Carcinoma, Hepatocellular/pathology , Disease-Free Survival , Fatigue/etiology , Female , Humans , Liver Neoplasms/pathology , Male , Maximum Tolerated Dose , Middle Aged , Thalidomide/adverse effects , Treatment OutcomeABSTRACT
Although most physicians and the public are primarily concerned about the risk of transmitting human immunodeficiency virus (HIV) or hepatitis virus during a platelet transfusion, bacterial contamination is actually the most common infectious complication. Unlike red blood cells, platelets are stored at room temperature (20-24 degrees C), which raises the risk of bacterial proliferation. The risk of bacterial sepsis is 2.5-fold higher for each unit of transfused platelets compared to each unit of red blood cells. We report an unusual case of Streptococcus bovis septic shock associated with a contaminated platelet transfusion.
