Download the Free Unbound MEDLINE PubMed App to your smartphone or tablet.
Available for iPhone, iPad, iPod touch, and Android.
- Successful platelet count recovery in lupus-associated thrombocytopenia with the thrombopoietin agonist eltrombopag. [JOURNAL ARTICLE]
- Clin Rheumatol 2014 Apr 17.
Eltrombopag is a new thrombomimetic medication approved for the treatment of immune thrombocytopenia. There are very few reports on the use of eltrombopag in patients with thrombocytopenia associated with sytemic lupus.We present a recent case of a patient with lupus with severe thrombocytopenia refractory to conventional therapy and full recovery with the use of eltrombopag. The present status of the literature with the use of this medication in patients with lupus is reviewed and discussed.
- Phase I trial of everolimus, gemcitabine and cisplatin in patients with solid tumors. [JOURNAL ARTICLE]
- Invest New Drugs 2014 Apr 18.
Background A Phase I trial of the 2-drug regimen of everolimus plus gemcitabine (Cohort I) and the 3-drug regimen of everolimus plus gemcitabine and cisplatin (Cohort II) was performed to determine the maximally tolerated dose (MTD) of both combinations. An expansion cohort (Cohort III) of patients with cholangiocarcinoma or gallbladder carcinoma was treated at the MTD. Methods A standard 3 + 3 design dose escalation was used. Everolimus was given on Monday/Wednesday/Friday or daily depending upon the dose level. Gemcitabine and cisplatin were administered on days 1 and 8 of each 21 day cycle. Results Twelve patients were entered in Cohort I and 15 in Cohort II. The MTD for Cohort I was everolimus 5 mg on Monday/Wednesday/Friday and gemcitabine 800 mg/m(2). For Cohort II, it was everolimus 5 mg on Monday/Wednesday/Friday, gemcitabine 600 mg/m(2), and cisplatin 12.5 mg/m(2). All DLTs in this study were hematologic. Complete responses (CR) were seen in a patient with primary peritoneal carcinoma and another with recurrent pancreatic cancer. Partial responses (PR) were seen in 3 patients: breast, ampullary carcinoma and pheochromocytoma. Of 10 patients enrolled in Cohort III, six patients had stable disease and 4 had progressive disease. Conclusions This Phase I clinical trial has demonstrated that these 2-drug and 3-drug combinations are generally well tolerated and safely administered. The main DLTs in both regimens were hematologic, specifically thrombocytopenia. The 3-drug combination can be considered as a platform for future studies in specific tumor types.
- Feasibility and safety of a reduced duration of therapy of colony-stimulating factor in a dose-dense regimen. [JOURNAL ARTICLE]
- Support Care Cancer 2014 Apr 17.
The risk of febrile neutropenia (FN) in cancer patients receiving chemotherapy is mainly due to the type of chemotherapy regimen and the presence of specific risk factors in patients. The recent trend of using a dose-dense treatment schedule has enhanced the risk of FN. In the present prospective study, we evaluated the feasibility of a reduction of duration of therapy with colony-stimulating factor (G-CSF) in a dose-dense regimen.Between June 2002 and December 2011, 107 patients with a new diagnosis of non-Hodgkin lymphoma (NHL) receiving dose-dense chemotherapy, every 14 days, were included in the study. The primary endpoint was defined as the completion of planned chemotherapy cycles as scheduled. Secondary endpoints were median number of administered G-CSF doses (vials), incidence of FN, hospitalization and toxicity.The planned chemotherapy cycles (primary endpoint) were completed by 84.1 % of patients. The median number of G-CSF (lenograstim) doses administered for each patient was 24 (range 10-35), which corresponds to a median of five vials (range 0-10) for each cycle. Grades 3-4 toxicities, related to G-CSF administration, included neutropenia and thrombocytopenia (14.0 and 1.9 %, respectively). No grades 3-4 bone pain was detected. The incidence of FN and hospitalization was 9.3 % (10/107) and 4.5 % (5/107), respectively.Reduced dosage of G-CSF allows dose-dense chemotherapy scheduling, limits exposure to G-CSF and also represents an opportunity for cost savings.
- Heparin: Induced thrombocytopenia: Incidence and laboratory approach to diagnosis in Indians. [Journal Article]
- Indian J Pathol Microbiol 2014 Jan-Mar; 57(1):31-8.
Background and objectives: One of the most common complications of heparin administration is heparin-induced thrombocytopenia (HIT) which can also lead to catastrophic thrombotic events. The problem of identifying the cause of thrombocytopenia, as due to heparin, in patients with multiple co-morbid conditions is very essential for management. Thus, the laboratory investigations for diagnosis of HIT play a pivotal role. The objective of the study was to arrive at the incidence of HIT in ethnic Indian population and provide a decision after analysis of tests used to diagnose HIT. Materials and
Methods:125 consecutive patients (Power of study being 80%) undergoing open heart surgery and receiving unfractionated heparin were taken as subjects. Blood samples were collected a day before the surgery and days 1, 3, 5 and 7 after surgery. The cases were categorized into probable and unlikely groups depending on the clinical presentation and degree fall of platelet count. Anti-heparin PF4-associated antibodies were detected using rapid-ID gel microtyping system and ELISA tests. HIT was also tested using functional assays:- heparin-induced platelet aggregation test (PAT) and the rapid luminographic assay of heparin-induced ATP release.
Results:Of the 125 patients, 11 patients were clinically labeled as probable HIT and 29 patients were clinically labeled as unlikely HIT. There were seven confirmed cases of HIT cases that were positive for one functional and one immunological assay. Only one case of HITT was encountered. Accordingly, the incidence of HIT was found to be 5.6 % and that of HITT to be 0.8%. ELISA tests were positive in 21 cases (17%) which demonstrated the presence of anti-HPF4 antibodies in non-HIT cases as well. It was found that the rapid gel test had sensitivity comparable to functional assay with better specificity than ELISA. Interpretation and conclusions: Incidence of HIT in ethnic Indian population is 5.6%. Patients with a drop of >50% in platelet count should be perused as a likely candidate of HIT. These cases should be subjected to the ID-HPF4 antibody assay as this is a rapid test, can be done for individual cases, and has better specificity and similar sensitivity than ELSIA. Cases with clinically probable HIT and a positive ID-HPF4 assay can be taken as confirmed cases of HIT. However, cases clinically unlikely for HIT and a positive ID-HPF4 assay should be subjected to another test to establish the diagnosis of HIT.
- Person-to-Person Asymptomatic Infection of Severe Fever with Thrombocytopenia Syndrome Virus through Blood Contact. [Journal Article]
- Intern Med 2014; 53(8):903-6.
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease recently discovered in northeastern and central China that is caused by a novel bunyavirus, severe fever with thrombocytopenia syndrome virus (SFTSV). Humans are primarily infected through tick bites. Four previous reports have discussed SFTS infection from person to person, all cases of which were symptomatic. In this report, we analysed the epidemiological and clinical data for a cluster of cases, including one case of secondary-asymptomatic infection, and review the literature regarding SFTSV transmission from person to person. We conclude that SFTSV caused the asymptomatic infections via person-to-person contact with infected blood.
- Intermittent granulocyte colony-stimulating factor for neutropenia management in patients with relapsed or refractory multiple myeloma treated with lenalidomide plus dexamethasone. [JOURNAL ARTICLE]
- Leuk Lymphoma 2014 Apr 17.
ABSTRACT Neutropenia is a major dose-limiting toxicity associated with lenalidomide use for relapsed/refractory multiple myeloma (MM). The efficacy and optimal dosing schedule of granulocyte colony-stimulating factor (G-CSF) are unclear. In order to economize on G-CSF use, we developed an intermittent G-CSF schedule (4-6 doses in weeks 3-4 every 28-day cycle), initiated upon onset of grade 3-4 neutropenia. Of 216 relapsed/refractory MM patients treated at our center with lenalidomide/dexamethasone on an Expanded Access Program protocol (median follow-up of 17 months), there was a high incidence of grade 3-4 neutropenia (61%) and grade 3-4 infections (37%). Despite intermittent G-CSF use in 117 patients, recurrent grade 3-4 neutropenia was common (59%), and subsequent dose reductions were required in 40% of G-CSF recipients, most due to thrombocytopenia or mixed cytopenias. G-CSF recipients had a longer duration on therapy (median 10.4 vs 3.7 months; p=0.01) and achieved a higher rate and depth of response. Intermittent G-CSF therefore may be an effective approach for lenalidomide dose-preservation which may lead to improved outcomes, although it does not prevent infections nor dose-limitations due to thrombocytopenia.
- Idarubicin-loaded beads for chemoembolisation of hepatocellular carcinoma: results of the IDASPHERE phase I trial. [JOURNAL ARTICLE]
- Aliment Pharmacol Ther 2014 Apr 16.
A phase I dose-escalation trial of transarterial chemoembolisation (TACE) with idarubicin-loaded beads was performed in cirrhotic patients with hepatocellular carcinoma (HCC).To estimate the maximum-tolerated dose (MTD) and to assess safety, efficacy, pharmacokinetics and quality of life.Patients received a single TACE session with injection of 2 mL drug-eluting beads (DEBs; DC Bead 300-500 μm) loaded with idarubicin. The idarubicin dose was escalated according to a modified continuous reassessment method. MTD was defined as the dose level closest to that causing dose-limiting toxicity (DLT) in 20% of patients.Twenty-one patients were enrolled, including nine patients at 5 mg, six patients at 10 mg, and six patients at 15 mg. One patient at each dose level experienced DLT (acute myocardial infarction, hyperbilirubinaemia and elevated aspartate aminotransferase (AST) at 5-, 10- and 15-mg, respectively). The calculated MTD of idarubicin was 10 mg. The most frequent grade ≥3 adverse events were pain, elevated AST, elevated γ-glutamyltranspeptidase and thrombocytopenia. At 2 months, the objective response rate was 52% (complete response, 28%, and partial response, 24%) by modified Response Evaluation Criteria in Solid Tumours. The median time to progression was 12.1 months (95% CI 7.4 months - not reached); the median overall survival was 24.5 months (95% CI 14.7 months - not reached). Pharmacokinetic analysis demonstrated the ability of DEBs to release idarubicin slowly.Using drug-eluting beads, the maximum-tolerated dose of idarubicin was 10 mg per TACE session. Encouraging responses and median time to progression were observed. Further clinical investigations are warranted (NCT01040559).
- A case of severe thrombocytopenia associated with acute HIV-1 infection. [JOURNAL ARTICLE]
- Int J STD AIDS 2014 Apr 15.
A 23-year-old man was admitted to our hospital with severe thrombocytopenia. He had unprotected sexual contact 6 weeks earlier. He was diagnosed with acute HIV infection by means of HIV RNA viral load testing and HIV-associated thrombocytopenia. Although thrombocytopenia improved immediately with short-term dexamethasone therapy, this effect was not sustained after cessation of therapy. Antiretroviral therapy including raltegravir was initiated, and the patient recovered from severe thrombocytopenia within several days. The findings from this case suggest that acute HIV infection should be suspected with unexplained thrombocytopenia, and that antiretroviral therapy is the treatment of choice for severe HIV-associated thrombocytopenia, even when in the early period following acquisition of the virus.
- A Phase I Dose Escalation Study of Oral c-MET Inhibitor Tivantinib (ARQ 197) in Combination with Gemcitabine in Patients with Solid Tumors. [JOURNAL ARTICLE]
- Ann Oncol 2014 Apr 15.
Tivantinib (ARQ 197) is an orally available, non-ATP competitive, selective c-MET inhibitor. The primary objective of this study was to evaluate the safety, tolerability and to establish the recommended phase 2 dose (RP2D) of tivantinib and gemcitabine combination.Patients with advanced or metastatic solid tumors were treated with escalating doses of tivantinib (120 mg - 360 mg capsules) in combination with gemcitabine (1000 mg/m(2) weekly for 3 of 4 weeks). Different schedules of administration were tested and modified based on emerging preclinical data. Tivantinib was given continuously, twice a day (BID) for 2 weeks, 3 weeks, or 4 weeks of a 28-day cycle or on a 5-day on, 2-day off schedule (the day before and day of gemcitabine administration).Twenty-nine patients were treated with gemcitabine and escalating doses of tivantinib: 120 mg BID (n=4), 240 mg BID (n=6) and 360 mg BID (n=19). No dose limiting toxicities (DLT's) were observed in escalation. The RP2D was 360 mg BID daily, and 45 additional patients were enrolled in the expansion cohort. Grade ≥3 treatment-related toxicities were observed in 54/74 (73%) patients with the most common being neutropenia (43%), anemia (30%), thrombocytopenia (28%) and fatigue (15%). There was one treatment-related death due to neutropenia. Administration of gemcitabine did not affect tivantinib concentration. Fifty-six patients were evaluable for response. Eleven (20%) patients achieved a partial response (PR) and 26 (46%) had stable disease (SD), including 15 (27%) who achieved SD for over four months. Ten of 37 patients with clinical benefit had prior exposure to gemcitabine.The combination of tivantinib at its monotherapy dose and standard dose gemcitabine was safe and tolerable. Early signs of anti-tumor activity may warrant further development of this combination in non small cell lung cancer (NSCLC), ovarian, pancreatic and cholangiocarcinoma.ClinicalTrials.gov Identifier. NCT00874042.