Efficacy and safety of tositumomab and iodine-131 tositumomab (Bexxar) in B-Cell lymphoma, progressive after rituximab

Stanford University, Stanford, CA 94305-5821, USA.
Journal of Clinical Oncology (Impact Factor: 17.88). 03/2005; 23(4):712-9. DOI: 10.1200/JCO.2005.07.040
Source: PubMed

ABSTRACT To determine overall response (OR) and complete response (CR) rates, response duration, progression-free (PFS) and overall survival and safety with the tositumomab and iodine-131 tositumomab ((131)I tositumomab) therapeutic regimen in patients with indolent, follicular large-cell, or transformed B-cell lymphoma, progressive after rituximab.
From July 1998 to November 1999, 40 patients (24 rituximab nonresponders: 11 with response < 6 months, and five with response > or = 6 months) received a therapeutic dose (0.65 to 0.75 Gy per platelet count) of (131)I tositumomab based on total-body dosimetry in this prospective phase II study. The median number of prior treatments was four; 59% of patients were chemotherapy-resistant.
Confirmed OR (65%) and CR (38%) rates were not significantly associated with prior rituximab response. With a median follow-up of 3.3 years, the median PFS was 10.4 months, 24.5 months for responders, and not reached for CR patients. Among follicular grade 1 or 2 patients with tumors < or = 7 cm (n = 21), the OR and CR rates were 86% and 57%. Estimated 3-year PFS in this subgroup was 48%, compared with 11% for all others (P = .002). Transient grade 3 to 4 marrow toxicity was seen in 50% of patients. Two patients, one of whom received two subsequent chemotherapy regimens, developed secondary myelodysplasia.
(131)I tositumomab is effective in CD20-positive lymphoma progressive after rituximab, with a 65% OR rate and median PFS of 24.5 months for responders. Patients with follicular grade 1 or 2 histology and tumors < or = 7 cm achieved very high OR and CR rates, with 48% PFS at 3 years.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Cancer is a leading cause of death worldwide. Currently available therapies are inadequate and spur demand for improved technologies. Rapid growth in nanotechnology towards the development of nanomedicine products holds great promise to improve therapeutic strategies against cancer. Nanomedicine products represent an opportunity to achieve sophisticated targeting strategies and multi-functionality. They can improve the pharmacokinetic and pharmacodynamic profiles of conventional therapeutics and may thus optimize the efficacy of existing anti-cancer compounds. In this review, we discuss state-of-the-art nanoparticles and targeted systems that have been investigated in clinical studies. We emphasize the challenges faced in using nanomedicine products and translating them from experimental conditions to the clinical setting. Additionally, we cover aspects of nanocarrier engineering that may open up new opportunities for nanomedicine products in the clinic. Copyright © 2014. Published by Elsevier B.V.
    Journal of Controlled Release 12/2014; 200. DOI:10.1016/j.jconrel.2014.12.030 · 7.26 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The potential use of radionuclides in therapy has been recognized for many decades. A number of radionuclides, such as iodine-131 ((131)I), phosphorous-32 ((32)P), strontium-90 ((90)Sr), and yttrium-90 ((90)Y), have been used successfully for the treatment of many benign and malignant disorders. Recently, the rapid growth of this branch of nuclear medicine has been stimulated by the introduction of a number of new radionuclides and radiopharmaceuticals for the treatment of metastatic bone pain and neuroendocrine and other malignant or non-malignant tumours. Today, the field of radionuclide therapy is enjoying an exciting phase and is poised for greater growth and development in the coming years. For example, in Asia, the high prevalence of thyroid and liver diseases has prompted many novel developments and clinical trials using targeted radionuclide therapy. This paper reviews the characteristics and clinical applications of the commonly available therapeutic radionuclides, as well as the problems and issues involved in translating novel radionuclides into clinical therapies.
    Journal of Zhejiang University SCIENCE B 10/2014; 15(10):845-63. DOI:10.1631/jzus.B1400131 · 1.29 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To investigate the safety and treatment response of radioimmunotherapy (RIT) in combination with radiofrequency ablation (RFA) for the treatment of VX2 tumor on rabbit. A total of 36 rabbits bearing VX2 tumor on the thigh were randomly assigned into 3 groups (group I: 1-2 cm; group II: 2-3 cm; group III: 3-4 cm) and 4 subgroups (A: as control, just puncture the tumor using the RFA electrode without power output; B: RFA alone; C: 131I-chTNT intratumoral injection alone; D: RFA+131I-chTNT intratumoral injection 3 days later). The variation of blood assay, weight and survival among different groups and subgroups were used to assess the treatment safety. Ultrasound (US) was used to monitor and assess the tumor response after treatment. According to the results of the weight and the blood assay among different groups, subgroups, and at two time points (one day before and the 16th day after treatment), no damages to the liver, kidney function and myelosuppression resulting from the treatment were found. No significant differences in survivals among the four subgroups (p = 0.087) were found. In addition, 131I-chTNT did not show significant inhibition effect on VX2 tumor progression according to US measurements. 131I-chTNT intratumoral injection alone or in combination with RFA is relatively safe for rabbit without significant toxicity and shows no significant effect on the survival. The treatment response is not as satisfactory as anticipated.
    PLoS ONE 05/2014; 9(5):e96539. DOI:10.1371/journal.pone.0096539 · 3.53 Impact Factor