Biomedical subjects

C F Meares

Publications and source records attributed to C F Meares.

148 records · Page 9Linked to original sources

PubMedDate not supplied

Radioimmunotherapy after chemotherapy compared to chemotherapy alone in the treatment of advanced ovarian cancer: a matched analysis.

Ovarian cancer has an overall five-year survival of around 30% in spite of complete remissions being obtained after optimal surgery and platinum-based chemotherapy. Previous studies have indicated a survival advantage for patients treated with radiolabelled monoclonal antibodies (radioimmunotherapy). We report here on the survival of patients who received single-dose intraperitoneal radioimmunotherapy after having achieved complete remission with standard management. Twenty-five patients with epithelial ovarian cancer, stages Ic-IV, received adjuvant intraperitoneal radioimmunotherapy following completion of conventional chemotherapy. On achieving complete remission they receive once 25 mg of HMFG1 labelled with 18 mCi/m2. Controls for cases were sought from the database of the North Thames ovary group (NTOG). Controls were selected on the basis of stage, histological grade and type, and age of patient at diagnosis. Kaplan-Meier survival plots were constructed for cases and controls and subjected to statistical analysis with the log-rank test. Additionally, using a database of 84 NTOG patients known to be disease-free at the end of chemotherapy, estimated survival curves were constructed using Cox's proportional hazards regression model. Close matches were found for 20 of the 25 patients. Median survival has not been reached at a median follow-up of 59 months for cases and 27 months for controls. Survival at five years is 80% for cases and 55% for controls (p=0.0035). The Cox model estimates long-term (10-year) survival of 70% for patients who received radioimmunotherapy, compared to 32% for those that did not (p=0.003). All patients developed serological evidence of human anti-mouse antibody (HAMA). This study shows a likely survival benefit for patients with ovarian cancer who receive intraperitoneal radioimmuno-therapy in the adjuvant setting.

Adult↗

PubMedDate not supplied

Pharmacokinetics of indium-111 BLEDTA in man.

111In-BLEDTA is a bleomycin-containing radiopharmaceutical that has proven useful as a tumor imaging agent. Whole blood distribution and pharmacokinetic parameters were studied in nine cancer patients, and the results compared with previously reported studies using 57Co-bleomycin. In eight patients studied by bolus intravenous injection, 111In-BLEDTA had a beta half-life (t1/2 beta) of 1.3 hours, a terminal-phase half-life (t1/2) of 11.7 hours, a volume of distribution (Vd gamma) of 57.5L/m2, a total body clearance rate (C1b) of 52.8 ml/min/m2, a renal clearance rate (C1r) of 23.3 ml/min/m2, and a 24-hour urinary excretion of 38.1% total administered dose. 111In-BLEDTA and 57Co-bleomycin have similar C1bs but differing Vds. Polymorphonuclear cell uptake of 111In-BLEDTA may explain its shorter t1/2 beta and t1/2, as well as its lower C1r and 24-hour urinary excretion. While the biologic characteristics of 111In-BLEDTA contribute to a greater background activity than is observed in scans with 57Co-bleomycin, its superior physical properties render it clinically more desirable as a tumor-imaging radiopharmaceutical.

Adult↗

PubMedDate not supplied

Yttrium-90/indium-111-DOTA-peptide-chimeric L6: pharmacokinetics, dosimetry and initial results in patients with incurable breast cancer.

BACKGROUND: Radioimmunotherapy (RIT) using 131I-Chimeric L6 (ChL6) antibody has shown therapeutic promise for patients with breast cancer. To enhance this potential, a novel immunoconjugate was developed that targets adenocarcinomas like breast cancer and tightly binds yttrium-90 (90Y) for therapy and indium-111 (111In) for imaging. The radioimmunoconjugate consists of a macrocyclic chelator (DOTA) linked to ChL6 by a catabolizable peptide. 90Y-DOTA-peptide-ChL6 was designed to minimize the radiation dose to critical normal tissues, thereby improving the therapeutic index. MATERIALS AND METHODS: Three patients with incurable metastatic breast cancer received 90Y/111In-DOTA-peptide-ChL6 for 5 pharmacokinetics/dosimetry studies and one of these patients also received 2 therapy doses. Quantitative imaging of 111In and in vitro assay of 90Y and 111In in blood urine and bone marrow samples were obtained. RESULTS: 90Y/111In-DOTA-peptide-ChL6 was prepared at high purity and was stable in vivo. Assays of bone marrow revealed no evidence for escape of 90Y or 111In from the chelate. 111In imaging of tumors was excellent, providing a therapeutic index for tumor to marrow radiation as high as 229 to 1. 90Y and 111In provided comparable pharmacokinetics, as did tracer and therapeutic doses of radioimmunoconjugates. One patients that received 2 therapeutic doses of 90Y-DOTA-peptide-ChL6 showed regression of tumors and tumor markers. Toxicities were relatively minor and no anti-globulin response developed despite 5 immunoconjugate infusions. CONCLUSIONS: This first study in patients of radioimmunoconjugates with a catabolizable linker between the metal chelator and the antibody confirmed that these novel 90Y/111In-DOTA-peptide-ChL6 radioimmunoconjugates have significant potential. Tracer doses of 111In-DOTA-peptide-ChL6 for imaging predicted the behavior of therapeutic doses of 90Y-DOTA-peptide-ChL6. The latter radioimmunoconjugate induced regression of tumors and tumor markers without significant toxicity. When compared to earlier 131I-ChL6 dosimetry, 90Y-DOTA-peptide-ChL6 provided a therapeutic index several times better.

Antibodies, Monoclonal↗

PubMedDate not supplied

Maximum tolerated dose of 67Cu-2IT-BAT-LYM-1 for fractionated radioimmunotherapy of non-Hodgkin's lymphoma: a pilot study.

PURPOSE: Lym-1, a monoclonal antibody (MoAb) that preferentially targets malignant lymphocytes, has induced therapeutic responses in patients with non-Hodgkin's lymphoma (NHL) when labeled with iodine-131 (131I). Radiometal labeled antibodies provide a higher tumor radiation dose than the corresponding 131I labeled antibodies. Based on the strategy of fractionating the total radiation dose, this study was designed to define the maximum tolerated dose (MTD) of the first 2, of a maximum of 4, doses of 67Cu-2IT-BAT-Lym-1 given 4 weeks apart. Additionally, toxicity, radiation dosimetry and efficacy were assessed. MATERIALS AND METHODS: Patients had Ann Arbor stage IVB NHL, resistant to standard therapy, including multiple chemotherapy regimens. Each dose of 67Cu-2IT-BAT-Lym-1 was given after a preload of unmodified Lym-1. A 10 mCi imaging dose of 67Cu-2IT-BAT-Lym-1 was given in order to assess pharmacokinetics and radiation dosimetry prior to therapy. Based on the MTD for 131I-Lym-1 and comparative dosimetry for 131I-Lym-1 and 67Cu-2IT-BAT-Lym-1, the trial was initiated at 60 millicuries per square meter of body surface area (mCi/m2) in cohorts of 3 patients. RESULTS: A single cohort of patients proved sufficient to define the MTD as 60 mCi/m2 for each of the first 2 doses of 67Cu-2IT-BAT-Lym-1. The dose-limiting toxicities were grade 3-4 thrombocytopenia and neutropenia. Neutropenic sepsis and bleeding did not occur. Mean radiation dose contributed to the bone marrow by 67Cu in the body and blood was 0.2 (range, 0.2 to 0.3) rads/mCi. Copper-67 incorporated into ceruloplasmin contributed 25% of the dose to marrow from blood. Non-hematologic toxicities did not exceed grade 2. The three patients had substantial tumor regression even after imaging doses of 67Cu-2IT-BAT-Lym-1. After therapy, one response was complete with a duration of 12 months. Radiation doses to tumors in this patient varied from 7.0-21.9 rads/mCi or 5420-7000 total rads from the course of therapy. CONCLUSION: 67Cu-2IT-BAT-Lym-1 provided good imaging, favorable radiation dosimetry and a remarkably high therapeutic index (ratio of tumor to marrow radiation doses). The non-myeloablative MTD for each of 2 doses was 60 mCi/m2.

Adult↗