Biomedical subjects

R E Coleman

Publications and source records attributed to R E Coleman.

At least 73 records · Page 4Linked to original sources

PubMed2001

Soldier acceptability of a camouflage face paint combined with DEET insect repellent.

Under operational conditions, current doctrine requires separate application of the standard military insect repellent and camouflage face paint. Working with an industrial partner, Amon Re, Inc., we developed a combined camouflage face paint and insect repellent that offers excellent protection from arthropod disease vectors. We undertook a study to determine whether the new product was acceptable to soldiers under field conditions. A new formulation of camouflage face paint containing the insect repellent N,N-diethyl-3-methyl-benzamide (DEET) was tested for user acceptability during a joint-service, multinational, military field training exercise (Operation Cobra Gold 1999) in Thailand. Soldiers testing the camouflage face paint were members of one of three companies (A, B, and C) of 1st Battalion, 21st Infantry Regiment, 25th Infantry Division. Soldiers in A company (N = 98) received standard military camouflage face paint and the U.S. military's Extended Duration Topical Insect and Arthropod Repellent containing 33% DEET, soldiers in B company (N = 75) received a new formulation of camouflage face paint without DEET, and soldiers in C company (N = 88) received the new formulation of camouflage face paint containing 30% DEET. Every soldier who volunteered to participate completed the study and submitted responses to the questionnaire. The different treatments were evaluated while soldiers spent 4 days conducting simulated combat exercises in a hot, tropical environment in central Thailand. Soldiers were provided the test materials, given a briefing on the study, and completed an initial questionnaire on May 19, 1999. Soldiers completed a final questionnaire after they returned from the training exercise on May 24, 1999. Results of the study indicated that soldiers found the new formulation of 30% DEET camouflage face paint easier to apply (88% of respondents) and remove (77%) than the current standard issue camouflage face paint. Soldiers liked the new 30% DEET camouflage face paint formulation better (61%) and were more likely to recommend it (67%) than the old camouflage face paint formulation. Although the addition of DEET to the camouflage face paint occasionally caused minor irritation after application for a short period (less than 15 minutes), the new camouflage face paint formulation with 30% DEET was evaluated most often (72%) as either good or excellent. The new 30% DEET camouflage face paint formulation offers significant operational advantages: protection from disease-transmitting arthropods, elimination of the need to carry separate insect repellent and camouflage face paint, and reduction in the time required to apply repellent and camouflage face paint separately.

Adolescent↗

PubMed2001

Synthesis and evaluation of (18)F-labeled choline analogs as oncologic PET tracers.

UNLABELLED: Elevated levels of choline (trimethyl-2-hydroxyethylammonium) and choline kinase (CK) activity in neoplasms have motivated the development of positron-labeled choline analogs for noninvasive detection of cancer using PET. The aim of this study was to further evaluate [(18)F]fluorocholine (fluoromethyl-dimethyl-2-hydroxyethylammonium [FCH]) as an oncologic probe in comparison with several other closely related molecules. METHODS: FCH, [(18)F]fluoromethyl-methylethyl-2-hydroxyethylammonium (FMEC), [(18)F]fluoroethyl-dimethyl-2-hydroxyethylammonium (FEC), and [(18)F]fluoropropyl-dimethyl-2-hydroxyethylammonium (FPC) were synthesized through [(18)F]fluoroalkylation reactions. In vitro phosphorylation rates of the (18)F-labeled choline analogs and [methyl-(14)C]choline (CH) were studied using yeast CK. Several choline radiotracers were also evaluated in cultured PC-3 human prostate cancer cells. Data on chemical stability, radiation dosimetry, and toxicity of FCH were obtained. PET studies with FCH were performed on a patient with prostate cancer and a patient with a brain tumor. RESULTS: FCH and FMEC revealed in vitro phosphorylation by CK that was similar to that of choline, whereas rates of phosphorylation of FEC and FPC were 30% (P < 0.01) and 60% (P < 0.01) lower, respectively. Accumulations of FCH, CH, and FPC in cultured PC-3 cancer cells were comparable, whereas uptake of FEC was approximately one fifth that of FCH. Dosimetry estimates using FCH biodistribution data in mice indicated that the kidneys are radiation-dose-critical organs for FCH. PET images of a patient with recurrent prostate cancer showed uptake of FCH in the prostatic bed and in metastases to lymph nodes. FCH PET showed uptake in malignancies in a patient with metastatic breast cancer. PET revealed FCH uptake in biopsy-proven recurrent brain tumor with little confounding uptake by normal brain tissues. CONCLUSION: The fluoromethyl choline analog FCH may serve as a probe of choline uptake and phosphorylation in cancer cells, whereas fluoroethyl (FEC) and fluoropropyl (FPC) analogs appear to have relatively poorer biologic compatibility. Preliminary PET studies on patients with prostate cancer and with breast cancer and brain tumor support further studies to evaluate the usefulness of FCH as an oncologic probe.

Adult↗

PubMed2001

PET in lung cancer staging.

The primary clinical application of FDG-PET is in the evaluation of patients with lung cancer and includes diagnosis, staging and restaging of non-small cell lung cancer. PET has a very high accuracy (sensitivity = 97%, specificity = 78%) for characterizing nodules that are indeterminate by chest radiograph and computed tomography. The major utility of PET in the evaluation of patients with lung cancer is the staging of the entire body. PET is more accurate than the conventional imaging modalities of CT and bone scans in the detection of metastatic disease. PET is accurate in the staging of the mediastinum, adrenal glands, and the skeletal system. PET is not as accurate in the detection of brain metastases because of their small size and the normal cortical accumulation.

Carcinoma, Non-Small-Cell Lung↗

PubMed2001

Light, carbon dioxide, and octenol-baited mosquito trap and host-seeking activity evaluations for mosquitoes in a malarious area of the Republic of Korea.

Two field trials for commercially available and experimental mosquito traps variously baited with light, carbon dioxide, octenol, or combinations of these were evaluated in a malarious area at Paekyeon-Ri near Tongil-Chon (village) and Camp Greaves, Paju County, Kyonggi Province, Republic of Korea. The host-seeking activity for common mosquito species was determined using hourly aspirator collections from a human- and propane lantern-baited Shannon trap. The total number of mosquitoes and number of each species captured during the test were compared using 8 x 8 and 5 x 5 Latin square designs based on trap location. Significant differences were observed for the total number of mosquitoes collected in the 8 x 8 test, such that counterflow geometry (CFG) with CO2 > or = CFG with CO2 and octenol > or = Shannon trap > or = Mosquito Magnet with octenol > American Biophysics Corporation (ABC) light trap with light, CO2 (500 ml/min), and octenol > or = ABC light trap with light and dry ice > or = ABC light trap with light and CO2 > ABC light trap with light only. A concurrent 5 x 5 test found significant differences in trap catch, where Mosquito Magnet with octenol > New Jersey light trap > or = EPAR Mosquito Killer with CO2 > or = ABC light trap with light and dry ice > Centers for Disease Control (CDC) light trap (manufactured by John W. Hock) with light and octenol. Significant differences in trap catch were noted for several species including: Aedes vexans, Anopheles sinensis, An. yatsushiroensis, An. lesteri, Culex pipiens, and Cx. orientalis. Traps baited with octenol captured significantly fewer Cx. pipiens than those not baited with octenol. Likewise, no Cx. orientalis were captured in octenol-baited traps. Host-seeking activity showed a similar bimodal pattern for all species captured. Results from these field trap evaluations can significantly enhance surveillance efforts. Significantly greater numbers of mosquitoes were captured with mosquito traps using counterflow technology (e.g., Mosquito Magnet and CFG traps) when compared to standard light and carbon dioxide-baited traps. Additionally, field evaluations demonstrate that various traps can be utilized for isolation and detection of arboviruses and other pathogens.

Animals↗

PubMed2000

Phase I trial results of iodine-131-labeled antitenascin monoclonal antibody 81C6 treatment of patients with newly diagnosed malignant gliomas.

PURPOSE: To determine the maximum-tolerated dose (MTD) of iodine-131 ((131)I)-labeled 81C6 antitenascin monoclonal antibody (mAb) administered clinically into surgically created resection cavities (SCRCs) in malignant glioma patients and to identify any objective responses with this treatment. PATIENTS AND METHODS: In this phase I trial, newly diagnosed patients with malignant gliomas with no prior external-beam therapy or chemotherapy were treated with a single injection of (131)I-labeled 81C6 through a Rickham reservoir into the resection cavity. The initial dose was 20 mCi and escalation was in 20-mCi increments. Patients were observed for toxicity and response until death or for a minimum of 1 year after treatment. RESULTS: We treated 42 patients with (131)I-labeled 81C6 mAb in administered doses up to 180 mCi. Dose-limiting toxicity was observed at doses greater than 120 mCi and consisted of delayed neurotoxicity. None of the patients developed major hematologic toxicity. Median survival for patients with glioblastoma multiforme and for all patients was 69 and 79 weeks, respectively. CONCLUSION: The MTD for administration of (131)I-labeled 81C6 into the SCRC of newly diagnosed patients with no prior radiation therapy or chemotherapy was 120 mCi. Dose-limiting toxicity was delayed neurologic toxicity. We are encouraged by the survival and toxicity and by the low 2.5% prevalence of debulking surgery for symptomatic radiation necrosis.

Adult↗

PubMed2000

High dose chemotherapy: rationale and results in breast carcinoma.

BACKGROUND: High dose chemotherapy (HDC) with hematopoietic stem cell support is an increasingly important strategy in the management of advanced cancer. Early Phase II studies and the development of peripheral blood stem cell support to enable safe and tolerable myeloablative chemotherapy has resulted in its controversial and widespread use in the management of breast carcinoma. Recently, several randomized trials of both advanced breast carcinoma and the adjuvant setting have been reported. METHODS: The technical developments in HDC and results from the randomized clinical trials reported to date were reviewed. RESULTS: Three randomized trials of advanced breast carcinoma and five of high risk adjuvant patients were identified. Only two relatively small trials from South Africa have so far shown an advantage for high dose chemotherapy, and the validity of these trials has recently been seriously challenged. A Scandinavian adjuvant trial showed no advantage for HDC when compared with maximum nonablative doses supported with granulocyte-colony stimulating factor (G-CSF). Four trials were too small to detect clinically realistic differences in outcome, whereas the other large adjuvant trial was reported prematurely and the results in the HDC arm were dominated by high procedure-related mortality. CONCLUSIONS: It is difficult to make specific treatment recommendations based on the conclusions from the currently available data. The 1999 American Society of Clinical Oncology reports were inconsistent and in some cases were presented before the results were sufficiently mature to provide statistically reliable data. However, it is clear that, unlike in leukemia, lymphoma, and multiple myeloma, HDC in breast carcinoma should not be used outside the context of a clinical trial. The mature results of the ongoing trials are eagerly awaited, whereas the use of immediate as opposed to consolidation high dose treatment, tandem transplants, and developments in immunologic and genetic manipulation of the graft merit further evaluation.

Breast Neoplasms↗

PubMed2000

The role of lung perfusion imaging in predicting the direction of radiation-induced changes in pulmonary function tests.

BACKGROUND: The aim of this study was to determine whether preradiation (pre-RT) single photon emission computed tomography (SPECT) lung perfusion scans can be used to predict RT-induced changes in pulmonary function tests (PFTs). METHODS: Ninety-four patients irradiated for thoracic tumors had pre-RT SPECT lung perfusion scans. The presence of SPECT hypoperfusion distal to a central mediastinal tumor was qualitatively assessed visually without knowledge of PFT changes. Patients were grouped based on whether the diffusion capacity (DLCO) ever increased post-RT. Comparisons of patient groups were performed using 1-tailed Fisher exact tests. Patient follow-up was 6-56 months (mean, 30 months). To assess SPECT hypoperfusion objectively, the average dose to the computed tomography (CT)-defined lung was compared with the weighted-average dose (based on relative perfusion) to the SPECT-defined lung. The ratio between the CT- and SPECT-defined mean lung dose provided a quantitative assessment of hypoperfusion. The mean ratio for patients with central tumor and adjacent hypoperfusion was compared with that of the others (Wilcoxon rank-sum one-sided test). RESULTS: In patients with central tumors, 41% (9 of 22) with adjacent hypoperfusion had improvements in DLCO following radiation, versus 18% (3 of 17) of those without hypoperfusion (P = 0.11). In patients with lung carcinoma, the corresponding ratios were 40% (8 of 20) and 10% (1 of 10), respectively (P = 0.10). The mean ratio of CT dose to SPECT dose was 1.35 for patients with central tumors and adjacent hypoperfusion versus 1.16 for others (P = 0.017). CONCLUSIONS: The presence of SPECT hypoperfusion adjacent to a central mediastinal mass may identify patients likely to have improved PFTs following RT. Thus, SPECT imaging may be useful in models for predicting radiation-induced changes in PFTs.

Adult↗

PubMed2000

Dosimetry and dose-response relationships in newly diagnosed patients with malignant gliomas treated with iodine-131-labeled anti-tenascin monoclonal antibody 81C6 therapy.

PURPOSE: The objective of this study was to perform the dosimetry and evaluate the dose-response relationships in newly diagnosed patients with malignant brain tumors treated by direct injections of (131)I-labeled 81C6 monoclonal antibody (MAb) into surgically created resection cavities (SCRCs). METHODS AND MATERIALS: Absorbed doses to the 2-cm-thick shell as measured from the margins of the resection cavity interface were estimated for 42 patients with primary brain tumors. MR images were used to assess the enhanced-rim volume as a function of time after radiolabeled MAb therapy. Biopsy samples were obtained from 15 patients and 1 autopsy. RESULTS: The average absorbed dose [range] to the 2-cm shell region was 32 [3-59] Gy. For the endpoint of minimal time to MR contrast enhancement, the optimal absorbed dose and initial dose-rate were 43 +/- 16 Gy and 0. 41 +/- 0.10 Gy/h, respectively. There was a correlation between the absorbed dose and dose rate to the shell region and biopsy outcome (tumor recurrence, radionecrosis, and tumor recurrence and/or radionecrosis). In this Phase I study, the maximum tolerated dose (MTD) was 120 mCi. At this MTD, the estimated average absorbed dose and initial dose rate to the 2-cm shell were 41 [9-89] Gy and 0.51 [0.24-1.13] Gy/h, respectively. These values are in agreement with the optimal values based on the time to MR lesion rim enhancement. CONCLUSIONS: The average absorbed dose to the 2-cm shell region varied considerably and mainly depended on cavity volume. In future clinical trials, the administered activity of (131)I-labeled 81C6 MAb may be adjusted based on cavity volume in order to deliver the optimal absorbed dose of 43 Gy rather than giving a fixed administered activity.

Antibodies, Monoclonal↗

PubMed2000

Fractal texture analysis of perfusion lung scans.

The purpose of this study is to investigate if fractal texture analysis can assist in the diagnostic interpretation of perfusion lung scans. Forty-five perfusion scans were acquired from patients with clinical suspicion of acute pulmonary embolism (PE) who underwent pulmonary angiography for final diagnosis. Fractal texture analysis was performed on 270 regions of interest (ROIs) extracted from the posterior view of the lung scans. Specifically, there were 94 normally perfused ROIs and 176 abnormal ROIs representing various lung diseases including PE and obstructive pulmonary disease (OPD). The average fractal dimension (FD) of normal ROIs was statistically significantly higher than that of abnormal ROIs. Furthermore, the FDs of abnormal ROIs with PE were significantly lower than the FDs of ROIs with OPD present.

Angiography↗

PubMed2000

Gestational trophoblastic disease: a study of mode of evacuation and subsequent need for treatment with chemotherapy.

OBJECTIVES: The aim of this study was to assess whether there was a change in the mode of evacuation of GTD over two time periods and to assess whether mode of evacuation influenced the subsequent need for chemotherapy. METHODS: A retrospective case note study of 4257 cases between 1986 and 1996, at a screening and treatment center managing GTD, was performed. RESULTS: Between the time periods 1986-1989 and 1990-1996 there was significant change in the mode of evacuation to suction curettage. The mode of evacuation was significant in determining the need for chemotherapy. The highest rate of chemotherapy was associated with medical methods of evacuation. CONCLUSIONS: Suction curettage is a safe method of uterine evacuation in GTD and its usage has increased with time. Medical methods of uterine evacuation are associated with higher rates of chemotherapy. This is probably due to a higher rate of incomplete evacuation. Medical methods of evacuation should not be used in cases of complete hydatiform mole.

Abortifacient Agents, Steroidal↗

PubMed2000

Characteristics of women with recurrent molar pregnancies.

OBJECTIVES: The aim of this study was to examine the incidence and characteristics of women who develop a second molar pregnancy after a previous episode of gestational trophoblastic disease. METHODS: A retrospective analysis was carried out on completed registration forms from referring hospitals in the North of England to the Sheffield Trophoblastic Screening Service over a 13-year period. All cases of second molar pregnancy were identified. Details of histology, blood group, ethnic origin, age, and subsequent pregnancies were examined. RESULTS: Between 1 January 1985 and 31 December 1997, 5030 patients were registered for follow-up and 275 (5.5%) required treatment for persistent disease. Thirty-five women had a subsequent molar pregnancy, a total of 0.70% of all registrations. There was no significant difference in age at first registration between those who were registered for one molar event and those who developed a subsequent molar pregnancy. The risk of a second molar event was highest in the second year after the initial diagnosis and reduced thereafter. There was a trend toward an increased risk of second molar pregnancy in Indian/Pakistani women when compared to Caucasian women (relative risk 2.4) but this was not significant at conventional levels. There was a significantly increased incidence of blood group B in patients that developed a molar pregnancy when compared to the normal population (P < 0.05), but there was no difference in distribution of blood group between those registered for their first molar event and those with two or more events. Patients who presented with a partial mole tended to have a partial mole as the second event but patients who presented with a complete mole were at risk of a subsequent complete mole, partial mole, or choriocarcinoma. Six percent of patients required chemotherapy for the second molar event, indicating no increase in aggressiveness in second moles. Two patients had three molar events. CONCLUSION: In the United Kingdom the risk of second molar pregnancy is less than 1%. There is an increased risk of molar pregnancy in women with blood group B and a trend toward an increased risk of second molar pregnancy in Indian/Pakistani women. Only 6% of patients required chemotherapy for the second mole; a second molar pregnancy is not an indication for chemotherapy.

ABO Blood-Group System↗

PubMed2000

Optimising treatment of bone metastases by Aredia(TM) and Zometa(TM).

Metastatic bone disease develops as a result of the many interactions between tumour cells and bone cells. This leads to disruption of normal bone metabolism, with the increased osteoclast activity seen in most, if not all, tumor types providing a rational target for treatment. The clinical course of metastatic bone disease in multiple myeloma, breast and prostate cancers is relatively long, with patients experiencing sequential skeletal complications over a period of several years. These include bone pain, fractures, hypercalcaemia, and spinal cord compression, all of which may profoundly impair a patient's quality of life. External beam radiotherapy and systemic endocrine and cytotoxic treatments are the mainstay of treatment in advanced cancers. However, it is now clear that the bisphosphonates provide an additional treatment strategy, which reduces both the symptoms and complications of bone involvement. Pamidronate (Aredia(TM)) is the most widely evaluated bisphosphonate and is recommended for most patients with multiple myeloma or breast cancer with bone metastases. Current research aims include the evaluation of new potent bisphosphonates such as zoledronic acid (Zometa(TM)). It is hoped that this compound is not only more convenient and easier to administer but also more effective in inhibiting skeletal morbidity. Zometa may also have some direct anticancer activity. Preclinical studies with Zometa have demonstrated its potential in malignant bone disease. Clinical studies in treatment of hypercalcemia of malignancy have been completed, as have Phase I and II trials in patients with cancer and pre-existing bone metastases. Three randomized, double-blind, controlled Phase III trials are now ongoing to establish the efficacy and safety of Zometa in treatment of bone metastases in patients with osteolytic and osteoblastic lesions. Additionally, new specific molecules such as osteoprotogerin have been developed that are based on our improved understanding of the cellular signalling mechanisms involved in cancer induced bone disease. These potent molecules are now entering clinical trials. Ongoing research is aimed at trying to define the optimum route, dose, schedule and type of bisphosphonate in metastatic bone disease and their use in the prevention and treatment of osteoporosis in cancer patients. In vitro suggestions of direct anti-cancer activity and some promising clinical data in early breast cancer have resulted in considerable interest in the possible adjuvant use of bisphosphonates to inhibit the development of bone metastases.

Antineoplastic Agents↗

PubMed2000

An experimental model of chronic myocardial hibernation.

BACKGROUND: Hibernating myocardium describes persistently impaired ventricular function at rest caused by reduced coronary blood flow. However, a realistic animal model reproducing this chronic ischemic state does not exist. The purpose of this study was to explore whether chronic low-flow hibernation could be produced in swine. METHODS: Miniswine underwent 90% stenosis of the left circumflex coronary artery. Positron emission tomography and dobutamine stress echocardiography were performed 3 and 30 days (n = 6) or 14 days (n = 4) after occlusion to evaluate myocardial blood flow and viability. Triphenyl tetrazolium chloride assessed percent infarction. Electron microscopy was used to identify cellular changes characteristic of hibernating myocardium. RESULTS: Positron emission tomography (13N-labeled-ammonia) 3 days after occlusion demonstrated a significant reduction in myocardial blood flow in the left circumflex distribution. This reduced flow was accompanied by increased glucose use (18F-fluorodeoxyglucose), which is consistent with hibernating myocardium. Thirty days after occlusion, positron emission tomography demonstrated persistent low flow with increased glucose use in the left circumflex distribution. Dobutamine stress echocardiography 3 days after occlusion demonstrated severe hypocontractility at rest in the left circumflex region. Regional wall motion improved with low-dose dobutamine followed by deterioration at higher doses (biphasic response), findings consistent with hibernating myocardium. The results of dobutamine stress echocardiography were unchanged 30 days after occlusion. Triphenyl tetrazolium chloride staining (n = 6) revealed a mean of 8% +/- 2% infarction of the area-at-risk localized to the endocardial surface. Electron microscopy (n = 4) 14 days after occlusion demonstrated loss of contractile elements and large areas of glycogen accumulation within viable cardiomyocytes, also characteristic of hibernating myocardium. CONCLUSIONS: Chronic low-flow myocardial hibernation can be reproduced in an animal model after partial coronary occlusion. This model may prove useful in the study of the mechanisms underlying hibernating myocardium and the use of therapies designed to improve blood flow to the heart.

Animals↗

PubMed2000

Induction of angiogenesis after TMR: a comparison of holmium: YAG, CO2, and excimer lasers.

BACKGROUND: Transmyocardial laser revascularization (TMR) is an emerging treatment for end-stage coronary artery disease. A variety of lasers are currently available to perform the procedure, although their relative efficacy is unknown. The purpose of this study was to compare changes in myocardial blood flow and function 6 months after TMR with holmium:yttrium-aluminum-garnet (holmium:YAG), carbon dioxide (CO2), and xenon chloride excimer lasers in a model of chronic ischemia. METHODS: Miniswine underwent subtotal (90%) left circumflex coronary stenosis. Baseline positron emission tomography and dobutamine stress echocardiography were performed to document hibernating myocardium in the left circumflex coronary artery distribution. Animals were then randomized to sham redo-thoracotomy (n = 5) or TMR using a holmium:YAG (n = 5), CO2 (n = 5) or excimer (n = 5) laser. Six months postoperatively, the positron emission tomography and dobutamine stress echocardiography studies were repeated and the animals sacrificed. RESULTS: In animals undergoing TMR with holmium: YAG and CO2 lasers, a significant improvement in myocardial blood flow to the lased left circumflex regions was seen. No significant change in myocardial blood flow was seen in sham- or excimer-lased animals. There was a significant improvement in regional stress function of the lased segments 6 months postoperatively in animals undergoing holmium:YAG and CO2 laser TMR that was consistent with a reduction in ischemia. There was no change in wall motion in sham- or excimer-lased animals. Significantly greater neovascularization was observed in the holmium:YAG and CO2 lased regions than with either the sham procedure or excimer TMR. CONCLUSIONS: Transmyocardial laser revascularization with either holmium:YAG or CO2 laser improves myocardial blood flow and contractile reserve in lased regions 6 months postoperatively. These changes were not seen following excimer TMR or sham thoracotomy, suggesting that differences in laser energy or wavelength or both may be important in the induction of angiogenesis.

Aluminum↗

PubMed2000

FDG imaging.

F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) imaging is being increasingly utilized in the detection of malignancy and in following the effects of therapy. FDG-PET imaging has been demonstrated to be accurate in the diagnosis of several malignancies including lung cancer, lymphoma, recurrent colorectal cancer, and recurrent melanoma. The initial studies evaluating FDG-PET in determining the effect of therapy reveal promising results. The clinical images are interpreted subjectively like other clinical nuclear medicine imaging studies. Semiquantitative indices such as the standardized uptake value may be used for research purposes to provide a quantitative parameter from the study.

Fluorodeoxyglucose F18↗

PubMed2000

Phase I open study of the effects of ascending doses of the cytotoxic immunoconjugate CMB-401 (hCTMO1-calicheamicin) in patients with epithelial ovarian cancer.

PURPOSE: We have performed a phase I study of the cytotoxic immunoconjugate CMB-401 in women with epithelial ovarian cancer (EOC). CMB-401 is a directed chemotherapy that comprises a genetically engineered human antibody against polymorphic epithelial mucin, to which is attached covalently two to three molecules, on average, of the cytotoxic antibiotic calicheamicin. The primary objectives of this two-centre study were to identify end-organ toxicities and to establish the maximum tolerated dose (MTD). PATIENTS AND METHODS: Thirty-four patients aged 37-75 years with progressive EOC not amenable to platinum/standard therapy, and with satisfactory WHO performance status (0-2) were recruited. Patients had received a mean of 3.2 previous chemotherapeutic regimens with a median interval since last chemotherapy of 182 days (range 34-1217). Patients received up to four cycles of a dual infusion of 35 mg/m2 hCTMO1 'predose' followed by doses of CMB-401 which were increased for each cohort--a regimen which minimises drug uptake in normal tissues whilst enhancing delivery to the ovarian tumour. CMB-401 dosing commenced at 2 mg/m2 and progressed via seven cohorts to 16 mg/m2. RESULTS: CMB-401 was generally well tolerated. However, transient fever and emesis occurred, necessitating routine prophylaxis, and increasingly significant malaise was reported as the dose increased. WHO grade 3-4 toxicities, irrespective of causality, included: anaemia 21%, granulocytopenia 9%, thrombocytopenia 9%, liver transaminases 3%, sepsis 3%, haemorrhage 6%, nausea/vomiting 76%; pulmonary 6%, and conscious state/somnolence 6%. The MTD was reached at 16 mg/m2. During the study four patients had a greater than 50% reduction in CA125, and three patients had radiological evidence of reduction in tumour bulk. CONCLUSIONS: CMB-401 appears to have an acceptable toxicity profile with demonstrable activity against EOC.

Adult↗

PubMed2000

Phase II study of docetaxel in patients with liver metastases from breast cancer. UK study group.

BACKGROUND: Previous phase II studies of docetaxel have indicated that hepatic metastases from breast cancer respond well to first-line treatment with docetaxel. The objective of this prospective, open label phase II study therefore was specifically to evaluate the activity and safety of docetaxel in this indication. PATIENTS AND METHODS: The study recruited 47 women (mean age 50 years, range 33-66 years) with hepatic metastases from breast cancer who fulfilled the eligibility criteria. After premedication with steroids, patients received a one-hour intravenous infusion of docetaxel 100 mg/m2 at three-weekly intervals for up to eight cycles. Response to treatment during medication was assessed after three, six and where appropriate, eight cycles and every three month follow-up thereafter, until disease progression or death. RESULTS: The best overall response rate (ORR) for evaluable patients was 64.3% (95% CI: 48.0-78.5%). In terms of the primary efficacy parameters, the ORR at the sixth cycle of treatment was 62% (95% CI: 45%-80%) with 17% complete responses. The median duration of response was 139 days (95% CI: 111-216 days) and the median survival duration calculated on an intent-to-treat basis was 335 days (227-568 days, 95% CI). One (2%) toxic death was reported. CONCLUSIONS: Docetaxel is a highly effective cytotoxic agent in the treatment of patients with liver metastases from breast cancer.

Adult↗

PubMed2000

Markers of bone turnover for the management of patients with bone metastases from prostate cancer.

Although increased bone formation is a prominent feature of patients with osteosclerotic metastases from prostate cancer, there is also some evidence for increased bone resorption. The aim of this study was to compare the clinical utility of new bone resorption markers to that of bone formation in patients with bone metastases from prostate cancer before and after bisphosphonate treatment. Thirty-nine patients with prostate cancer and bone metastasis, nine patients with prostate cancer without bone metastases, nine patients with benign prostatic hyperplasia and 355 healthy age-matched men were included. Urinary non-isomerized (alpha CTX) and beta isomerized (beta CTX) type I collagen C-telopeptides (CTX) and a new assay for serum CTX were used to assess bone resorption. Bone formation was determined by serum osteocalcin, serum total (T-ALP) and bone (BAP) alkaline phosphatase and serum type I collagen C-terminal propeptide (PICP). Fourteen patients with bone metastases were also evaluated 15 days after a single injection of the bisphosphonate pamidronate (120 mg). Levels of all bone formation and bone resorption markers were significantly (P < 0.006-0.0001) higher in patients with prostate cancer and bone metastasis than in patients with benign prostatic hyperplasia, patients with prostate cancer without bone metastases and healthy controls. In patients with bone metastases the median was increased by 67% for serum osteocalcin, 128% for T-ALP, 138% for BAP, 79% for PICP, 220% for urinary alpha CTX, 149% for urinary beta CTX and 214% for serum CTX. After bisphosphonate treatment all three resorption markers significantly decreased by an average of 65% (P = 0.001), 71% (P = 0.0010) and 61% (P = 0.0015) for urinary alpha CTX, urinary beta CTX and serum CTX, respectively, whereas no significant change was observed for any bone formation markers. Patients with prostate cancer and bone metastases exhibit a marked increase in bone resorption, which decreases within a few days of treatment with pamidronate. These findings suggest that these new resorption markers may be useful for the management of these patients.

Aged↗