Phase II study of picoplatin as second-line therapy for patients with small-cell lung cancer.

Purpose: This study was designed to confirm the efficacy and safety of picoplatin, a cisplatin analog designed to overcome platinum resistance, in patients with small-cell lung cancer (SCLC) with platinum-refractory/-resistant disease.

Patients And Methods: All patients received intravenous picoplatin 150 mg/m(2) every 3 weeks. Tumor response, progression-free survival, and overall survival were evaluated.

MIRD pamphlet No. 20: the effect of model assumptions on kidney dosimetry and response--implications for radionuclide therapy.

Unlabelled: Renal toxicity associated with small-molecule radionuclide therapy has been shown to be dose-limiting for many clinical studies. Strategies for maximizing dose to the target tissues while sparing normal critical organs based on absorbed dose and biologic response parameters are commonly used in external-beam therapy. However, radiopharmaceuticals passing though the kidneys result in a differential dose rate to suborgan elements, presenting a significant challenge in assessing an accurate dose-response relationship that is predictive of toxicity in future patients.

Results of a retrospective single institution analysis of targeted skeletal radiotherapy with (166)Holmium-DOTMP as conditioning regimen for autologous stem cell transplant for patients with multiple myeloma. Impact on transplant outcomes.

(166)Holmium-DOTMP is a beta-emitting radiophosphonate that localizes specifically to the bone surfaces and can deliver high-dose radiation to the bone marrow. Phase I/II trials showed feasibility and tolerability when combined with high-dose melphalan with or without total-body irradiation (TBI) in patients with multiple myeloma (MM) undergoing autologous stem cell transplantation (ASCT). The purpose of this study was to define the potential impact of (166)Holmium-DOTMP on outcomes in patients with MM undergoing ASCT.

166Ho-DOTMP radiation-absorbed dose estimation for skeletal targeted radiotherapy.

Unlabelled: 166Ho-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene-phosphonate (DOTMP) is a tetraphosphonate molecule radiolabeled with 166Ho that localizes to bone surfaces. This study evaluated pharmacokinetics and radiation-absorbed dose to all organs from this beta-emitting radiopharmaceutical.

Methods: After two 1.

Pretargeted radioimmunotherapy (RIT) with a novel anti-TAG-72 fusion protein.

Pretargeted radioimmunotherapy (RIT) increases the dose of radionuclide delivered to tumor sites while limiting radiation to normal tissues. The three components in Pretarget include a streptavidin-containing targeting molecule, a synthetic clearing agent (sCA), and (90)Y and/or (111)In-DOTA-biotin. This trial determined the feasibility and safety of using a genetically engineered fusion protein directed to TAG-72 as the targeting agent.

Patient-specific dosimetry of pretargeted radioimmunotherapy using CC49 fusion protein in patients with gastrointestinal malignancies.

Unlabelled: Pretargeted radioimmunotherapy (RIT) using CC49 fusion protein, comprised of CC49-(scFv)4 and streptavidin, in conjunction with 90Y/111In-DOTA-biotin (DOTA = dodecanetetraacetic acid) provides a new opportunity to improve efficacy by increasing the tumor-to-normal tissue dose ratio. To our knowledge, the patient-specific dosimetry of pretargeted 90Y/111In-DOTA-biotin after CC49 fusion protein in patients has not been reported previously.

Methods: Nine patients received 3-step pretargeted RIT: (a) 160 mg/m2 of CC49 fusion protein, (b) synthetic clearing agent (sCA) at 48 or 72 h later, and (c) 90Y/111In-DOTA-biotin 24 h after the sCA administration.

Testicular uptake and radiation dose in patients receiving Zevalin and Pretarget CC49Fusion protein.

Objective: Radiation dose to the testes from radionuclide therapies is of concern. This study evaluated image-quantification methods for testicular uptake in a phantom and in patients.

Methods: A 50-mL vial and a large water tank were used to simulate testes and the body, respectively.

Bone marrow dosimetry using blood-based models for radiolabeled antibody therapy: a multiinstitutional comparison.

Unlabelled: Standardization of marrow dosimetry is of considerable importance when estimating dose-response for a multicentered clinical trial involving radionuclide therapy. However, it is only within the past five years that the intercomparison of marrow dosimetry results among separate clinical trials that use the same agent has become scientifically feasible. In this work, we have analyzed reported marrow dosimetry results from radioimmunotherapy trials and recalculated marrow absorbed doses at a central facility using a standard blood model with patient-specific source data.

Clinical aspects of radiation nephropathy.

Small radiolabeled molecules are finding increasing clinical use for targeted radionuclide therapy. With the administration of radiolabeled small molecules, the bone marrow is not necessarily the first organ to show radiation toxicity. Rapid excretion of radioactivity through the urinary tract and the retention of radiolabeled small-protein molecules in the kidneys may expose the kidneys to radiation sufficient enough to cause toxicity--and in clinical trials, radiation toxicity of the urinary tract has become clinically relevant.

Dosimetry model for radioactivity localized to intestinal mucosa.

Background: This paper provides a new model for calculating radiation-absorbed doses to the full thickness of the small and large intestinal walls, and to the mucosal layers. The model was used to estimate the intestinal radiation doses from yttrium-90-labeled-DOTA-biotin binding to NR-LU-10-streptavidin in patients.

Methods: We selected model parameters from published data and observations, and used the model to calculate energy-absorbed fractions using the EGS4 radiation transport code.

Phase 1 trial of a novel anti-CD20 fusion protein in pretargeted radioimmunotherapy for B-cell non-Hodgkin lymphoma.

Pretargeted radioimmunotherapy (PRIT) has the potential to increase the dose of radionuclide delivered to tumors while limiting radiation to normal tissues. The purpose of this phase 1 trial is to assess safety of this multistep approach using a novel tetrameric single-chain anti-CD20-streptavidin fusion protein (B9E9FP) as the targeting moiety in patients with B-cell non-Hodgkin lymphoma (NHL), and to characterize its pharmacokinetics and immunogenicity. All patients received B9E9FP (160 mg/m(2) or 320 mg/m(2)); either 48 or 72 hours later, a synthetic clearing agent (sCA) was administered (45 mg/m(2)) to remove circulating unbound B9E9FP.

Dosimetry of high dose skeletal targeted radiotherapy (STR) with 166Ho-DOTMP.

A study was undertaken to determine the maximum tolerated dose of (166)Ho-DOTMP that could be administered safely, without negatively impacting marrow re-engraftment, in patients with multiple myeloma treated with melphalan prior to transplant. Ho-166 DOTMP is a tetraphosphonate that localizes rapidly to bone surface. The Ho-166 physical half-life is 26.

166Ho-DOTMP plus melphalan followed by peripheral blood stem cell transplantation in patients with multiple myeloma: results of two phase 1/2 trials.

Holmium-166 1, 4, 7, 10-tetraazcyclododecane-1, 4, 7, 10-tetramethylenephosphonate (166Ho-DOTMP) is a radiotherapeutic that localizes specifically to the skeleton and can deliver high-dose radiation to the bone and bone marrow. In patients with multiple myeloma undergoing autologous hematopoietic stem cell transplantation two phase 1/2 dose-escalation studies of high-dose 166Ho-DOTMP plus melphalan were conducted. Patients received a 30 mCi (1.

Dosimetry in a myeloablative setting.

In clinical therapy trials using high dosages of systemically administered radioactivity to treat cancer, myeloablation may occur. This is either an effect of the circulating radioactivity labeled to antibodies exposing the bone marrow to radiation, or it may occur because malignant cells in the bone marrow are targeted. Bone marrow cells may be targeted through antigens expressed on cells in the bone marrow or because radioactivity is targeted to the skeleton.