• Current treatment approaches for diffuse large B-cell lymphoma.

      Illidge, Timothy M; Tolan, Shaun; School of Cancer Imaging Sciences, CR UK Paterson Institute for Cancer Research, University of Manchester, Manchester M20 4BX, UK. tmi@manchester.ac.uk (2008-04)
      There have been two major developments over the last decade that has led to improvements in outcome and longer survival for patients with diffuse large B-cell lymphoma (DLBCL). These developments have been firstly to increase the dose of active cytotoxic drugs and shorten the time between cycles, resulting in dose-dense and/or dose-intense regimens and secondly the addition of the anti-CD20 monoclonal antibody rituximab to chemotherapy. Both strategies have been associated with higher response rates, lower relapse rates, longer event-free survival (EFS) and improved overall survival (OS), particularly in better prognostic groups. A combination of dose-dense and dose-intense chemotherapy regimens plus rituximab is currently being tested to confirm that the use of both approaches confers survival advantage. High-risk, poorer-prognosis DLBCL remains a challenge, and new treatment strategies are required for these patients. Improvements in outcome may potentially be achieved through a greater understanding of the genetic abnormalities specifically associated with poorer-prognosis disease, and factors that lead to unresponsiveness to chemotherapy. The role of radiotherapy is currently less clearly defined than at anytime in the management of DLBCL and the current evidence for using radiotherapy in this disease is therefore rigorously reviewed.
    • Evidence for extrathyroidal formation of 3-iodothyronamine in humans as provided by a novel monoclonal antibody-based chemiluminescent serum immunoassay.

      Hoefig, C S; Köhrle, J; Brabant, Georg E; Dixit, Kashinath C S; Yap, Beng K; Strasburger, C J; Wu, Z; Institut für Experimentelle Endokrinologie, Charité-Universitätsmedizin Berlin, Berlin, Germany. (2011-06)
      Thyronamines are thyronergic metabolites of thyroid hormones. Lack of reliable and sensitive detection methods for endogenous 3-iodothyronamine (3-T(1)AM) has so far hampered progress in understanding their physiological action and role in endocrine homeostasis or pathophysiology of diseases.
    • How have outcomes for patients with follicular lymphoma changed with the addition of monoclonal antibodies?

      Illidge, Timothy M; Chan, Clara; School of Cancer and Imaging Sciences, University of Manchester, Manchester, UK. tmi@manchester.ac.uk (2008-07)
      The outcome for patients with follicular lymphoma (FL) has substantially improved over the last few years. This improved survival appears to be largely related to the increasingly widespread use of anti-CD20 monoclonal antibody (mAb) rituximab in the therapy of FL today, either in combination with chemotherapy, for remission 'induction' and more recently as 'maintenance' therapy. Encouraging results have also been reported from radiolabelled anti-CD20 mAb or radioimmunotherapy (RIT), which exploits the unique method of action of this approach and high radiosensitivity of FL. High response rates and durable remissions have been seen with both (90)Y Ibritumomab tiuxetan and (131)I Tositumomab, and more recently compelling data are emerging demonstrating the efficacy of using these drugs as consolidation after initial treatment with chemotherapy or rituximab plus chemotherapy combinations. This review will focus on the current approaches and explore the data that has led to the emergence of a new nomenclature appearing in the language of clinicians involved in the treatment of FL, namely 'induction' therapy, 'consolidation' of initial response and 'maintenance' therapy. The current treatment approaches that have led to such increased optimism regarding the therapeutic outcome in FL are evaluated and discussed.
    • A phase I study of the safety and pharmacokinetics of the combination of pertuzumab (rhuMab 2C4) and capecitabine in patients with advanced solid tumors.

      Albanell, Joan; Montagut, Clara; Jones, Eileen T; Pronk, Linda; Mellado, Begoña; Beech, Janette; Gascon, Pere; Zugmaier, Gerhard; Brewster, Michael; Saunders, Mark P; et al. (2008-05-01)
      PURPOSE: To study the safety, pharmacokinetics, and recommended dose of the combination of pertuzumab, a humanized monoclonal antibody HER2-dimerization inhibitor, and capecitabine in patients with advanced malignancies. EXPERIMENTAL DESIGN: Patients that had progressed to standard treatment were treated with pertuzumab at a fixed dose of 1,050 mg given i.v. on day 1 plus capecitabine at doses of 825-1,000-1,250 mg/m(2), twice daily orally on days 1 to 14 of each 21-day treatment cycle, in three sequential cohorts. The pharmacokinetics of capecitabine and pertuzumab were studied. Patients received a single dose of capecitabine in a pretreatment phase (day -7) followed by serum sampling for capecitabine and its metabolites. RESULTS: Nineteen patients were accrued and 18 were assessable. The combination of capecitabine and pertuzumab was well tolerated at all dose levels and no dose-limiting toxicities were observed. The most frequent adverse event was asthenia, which was grade 3 in two patients. One asymptomatic pulmonary embolism occurred. No other grade 3 or 4 adverse events or cardiac or left ventricular ejection fraction events were reported. There was no apparent change in the pharmacokinetics of capecitabine and its metabolites when combined with pertuzumab. The pharmacokinetics of pertuzumab was apparently not modified when administered with capecitabine. Disease stabilization was observed in 11 patients. CONCLUSIONS: Pertuzumab and capecitabine were well tolerated at all dose levels. Escalation beyond the highest dose level tested was not planned, as this included the recommended doses of monotherapy for both drugs. In conclusion, this combination is ready for phase II testing.