Joseph E Eid

Publications (5)25.8 Total impact

• Article: A phase I study of weekly R1507, a human monoclonal antibody insulin-like growth factor-I receptor antagonist, in patients with advanced solid tumors.

  Razelle Kurzrock, Amita Patnaik, Joseph Aisner, Terri Warren, Stephen Leong, Robert Benjamin, S Gail Eckhardt, Joseph E Eid, Gerard Greig, Kai Habben, Cinara D McCarthy, Lia Gore
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  ABSTRACT: A phase I study was conducted to evaluate the pharmacokinetics, pharmacodynamics, safety, and tolerability of R1507-a fully human IgG1 type monoclonal antibody directed against the human insulin-like growth factor-I receptor. Experimental design: Patients with advanced solid tumors were assigned to receive i.v. R1507 weekly (qW), starting with 1 mg/kg. Subsequent cohorts were dosed at 3 and then 9 mg/kg. An additional 12 patients received 9 mg/kg R1507 qW. Patients remained on the study until the development of a dose-limiting toxicity or progressive disease. In total, 37 patients were treated with R1507 qW. No dose-limiting toxicities were identified and the maximum tolerated dose was not reached. The pharmacokinetics of R1507 were characterized by a slow clearance and limited volume of distribution, with an estimated elimination half-life justifying weekly administration. Serum IGF-I ligand levels increased proportionally to dose during the first 72 hours in all cohorts. R1507 was well tolerated. Two patients diagnosed with Ewing's sarcoma had partial responses of 11.5 and >26 months (ongoing at time of submission); 13 patients had stable disease; and 16 had progressive disease as best response by the Response Evaluation Criteria in Solid Tumors. R1507 is well tolerated and shows antitumor activity in patients with solid neoplasms, in particular Ewing's sarcoma. The recommended dose for the weekly schedule is 9 mg/kg qW.
  Clinical Cancer Research 04/2010; 16(8):2458-65. · 7.74 Impact Factor
• Article: A dose exploration, phase I/II study of administration of continuous erythropoietin receptor activator once every 3 weeks in anemic patients with multiple myeloma receiving chemotherapy.

  Anna Dmoszynska, Janusz Kloczko, Malgorzata Rokicka, Andrzej Hellmann, Ivan Spicka, Joseph E Eid
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  ABSTRACT: Continuous erythropoietin receptor activator (C.E.R.A.) is an innovative agent with unique erythropoietin receptor activity and a prolonged half-life, which has the potential for administration at extended dosing intervals. The objectives of this dose-finding study were to evaluate the hemoglobin (Hb) dose-response, pharmacokinetics, and safety of repeated doses of C.E.R.A. given once every 3 weeks to anemic patients with multiple myeloma (MM) receiving chemotherapy. This was an exploratory two-stage, open-label, parallel-group, multicenter study. Patients received C.E.R.A. doses of 1.0, 2.0, 3.5, 4.2, 5.0, 6.5, or 8.0 mg/kg once every 3 weeks by subcutaneous injection initially for 6 weeks, followed by a 12-week optional extension period. The primary outcome measures were the average Hb level and its change from baseline over the initial 6-week period, based on values of the slope of the linear regression analysis and the area under the curve. Rates of Hb response (defined as an increase in Hb of > or =2 g/dL without transfusion) and blood transfusion were also evaluated. Sixty-four patients entered the study. Dose-related increases in Hb levels were observed during the initial 6-week treatment period for C.E.R.A. doses of 1.0-4.2 mg/kg, with a similar response observed at higher doses. At least 70% of patients receiving 2.0-8.0 mg/kg of C.E.R.A. had Hb responses during the 18-week study. The elimination half-life of C.E.R.A. was found to be long (6.3-9.7 days [151.2-232.8 hours]). All doses were generally well tolerated. Based on its unique, long elimination half-life, C.E.R.A. has been demonstrated to be an effective and well-tolerated treatment of anemia given once every 3 weeks to patients with multiple myeloma receiving chemotherapy.
  Haematologica 04/2007; 92(4):493-501. · 6.42 Impact Factor
• Article: Phase II study of three dose levels of continuous erythropoietin receptor activator (C.E.R.A.) in anaemic patients with aggressive non-Hodgkin's lymphoma receiving combination chemotherapy.

  Anders Osterborg, Juan Luis Steegmann, Andrzej Hellmann, Stephen Couban, Jiri Mayer, Joseph E Eid
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  ABSTRACT: Anaemia is a common complication in the treatment of patients with aggressive non-Hodgkin lymphoma (NHL), but there are no published data on the effect of erythropoiesis-stimulating agents in such patients. This is the first open-label, phase II, dose-finding study to evaluate the efficacy and safety of continuous erythropoietin receptor activator (C.E.R.A.). Ninety-three anaemic patients with aggressive NHL who were receiving chemotherapy (including many advanced NHL, heavily pretreated patients) were randomised to receive 2.1, 4.2 or 6.3 microg/kg C.E.R.A. subcutaneously once every 3 weeks for 12 weeks. Haematopoietic response was achieved in 45%, 57% and 65% of patients at the respective dose level. During weeks 5-13, the mean haemoglobin changes from baseline in the intent-to-treat population were increases of 0.2, 2.4, and 5.7 g/l in the 2.1, 4.2, and 6.3 microg/kg treatment groups, respectively, and 4.4, 5.7 and 6.8 g/l in the per-protocol population at the respective dose levels. C.E.R.A. was generally well tolerated in all three groups. C.E.R.A. appeared to have dose-dependent clinical activity in most anaemic patients with aggressive NHL who were receiving chemotherapy.
  British Journal of Haematology 04/2007; 136(5):736-44. · 4.94 Impact Factor
• Source

  Available from: Rodryg Ramlau

  Article: Phase II study of two dose schedules of C.E.R.A. (Continuous Erythropoietin Receptor Activator) in anemic patients with advanced non-small cell lung cancer (NSCLC) receiving chemotherapy.

  Vera Hirsh, John Glaspy, Paul Mainwaring, Christian Manegold, Rodryg Ramlau, Joseph E Eid
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  ABSTRACT: C.E.R.A. (Continuous Erythropoietin Receptor Activator) is an innovative agent with unique erythropoietin receptor activity and prolonged half-life. This study evaluated C.E.R.A. once weekly (QW) or once every 3 weeks (Q3W) in patients with anemia and advanced non-small cell lung cancer (NSCLC) receiving chemotherapy. In this Phase II, randomized, open-label, multicenter, dose-finding study, patients (n = 218) with Stage IIIB or IV NSCLC and hemoglobin (Hb) <or= 11 g/dL were randomized to one of six treatment groups of C.E.R.A. administered subcutaneously for 12 weeks: 0.7, 1.4, or 2.1 microg/kg QW or 2.1, 4.2, or 6.3 microg/kg Q3W. Primary endpoint was average Hb level between baseline and end of initial treatment (defined as last Hb measurement before dose reduction or transfusion, or the value at week 13). Hematopoietic response (Hb increase >or= 2 g/dL or achievement of Hb >or= 12 g/dL with no blood transfusion in the previous 28 days determined in two consecutive measurements within a 10-day interval) was also measured. Dose-dependent Hb increases were observed, although the magnitude of increase was moderate. Hematopoietic response rate was also dose dependent, achieved by 51% and 62% of patients in the 4.2 and 6.3 microg/kg Q3W groups, and 63% of the 2.1 mug/kg QW group. In the Q3W group, the proportion of early responders (defined as >or= 1 g/dL increase in Hb from baseline during the first 22 days) increased with increasing C.E.R.A. dose, reaching 41% with the highest dose. In the 6.3 microg/kg Q3W group, 15% of patients received blood transfusion. There was an inclination for higher mean Hb increases and lower transfusion use in the Q3W groups than in the QW groups. C.E.R.A. was generally well tolerated. C.E.R.A. administered QW or Q3W showed clinical activity and safety in patients with NSCLC. There were dose-dependent increases in Hb responses. C.E.R.A. appeared to be more effective when the same dose over time was given Q3W than QW, with a suggestion that C.E.R.A. 6.3 microg/kg Q3W provided best efficacy in this study. However, further dose-finding studies using higher doses are required to determine the optimal C.E.R.A. dose regimen in cancer patients receiving chemotherapy.
  Trials 02/2007; 8:8. · 2.02 Impact Factor
• Article: Hydroxyurea-induced splenic regrowth in an adult patient with severe hemoglobin SC disease.

  Yiwu Huang, Thyagarajan Ananthakrishnan, Joseph E Eid
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  ABSTRACT: Hydroxyurea has been extensively used in patients with sickle cell anemia and severe sickle cell-hemoglobin C (SC) disease to reduce the severity of their diseases. We report here our experience with an adult patient with severe SC disease who developed symptomatic splenomegaly requiring splenectomy while being treated with hydroxyurea. This case suggests that hydroxyurea might restore some splenic function in functionally asplenic patients with sickle cell anemia or SC disease, but also raises the clinical concern that hydroxyurea may induce splenic regrowth, resulting in symptomatic splenomegaly. With the increasing use of hydroxyurea in the management of SS disease or other hemoglobinopathies, the importance of spleen monitoring must be further emphasized in these patients.
  American Journal of Hematology 11/2003; 74(2):125-6. · 4.67 Impact Factor