PubMed Health⌕ Search

Biomedical subjects

H Calvert

Publications and source records attributed to H Calvert.

At least 19 recordsLinked to original sources
PubMed2004

Surgical treatment of hepatic hydatid cyst.

Hydatid disease of the liver is caused by the tapeworm Echinococcus granulosus, and the highest incidence of human infestation occurs in sheep and cattle-raising areas. Although, still an uncommon occurrence, it is being seen with increasing frequency; hence, it is important that surgeons make themselves aware of the pathology and treatment of the disease. The liver is most commonly involved, although many other organs, including lungs and brain may also be affected. An echinococcal cyst of the liver was reported in a patient who is a resident in Northern Ireland but had originally lived and worked in mainland Britain. Details of the lifecycle, pathology, diagnostic techniques and surgical management of hydatid cysts are reviewed.

Adult↗
PubMed2003

Cancer drug development in Europe: a selection of new agents under development at the European Drug Development Network.

From may 99, three european leaders in anti-cancer drug development (EORTC, Cancer Research UK, SENDO) have got together to form a network of collaborating groups: the European Drug Development Network. The member organisations have all agreed to join their efforts in developing new drugs. They have acquired a great and efficient expertise in anticancer drug development covering all aspects from drug screening to refinement of trial methodology and translational research. In this paper, the most interesting drugs under development in each of the three organisations are being described and discussed.

Angiogenesis Inhibitors↗
PubMed2003

Phase II study of pemetrexed in breast cancer patients pretreated with anthracyclines.

BACKGROUND: To assess antitumor activity and toxicity of pemetrexed in metastatic breast cancer (MBC) patients previously treated with anthracyclines. PATIENTS AND METHODS: Seventy-seven MBC patients from 12 European institutions were entered into the study. Seventy-two patients were considered evaluable for response and toxicity. Forty-two patients were classified as anthracycline-failure (relapse >30 days after completion of a prior anthracycline regimen) and 30 as anthracycline-refractory (progression within 30 days after anthracycline therapy). Pemetrexed 600 mg/m(2) was administered intravenously every 3 weeks until progressive disease or unacceptable toxicity. RESULTS: There were three complete and 12 partial responders [response rate 21% (95% confidence interval 12%)]. Response rates in the anthracycline-failure and anthracycline-refractory groups were 24% and 17%, respectively. A subset of 31 patients pretreated with anthracyclines and taxanes had a response rate of 26%. Median duration of response and median survival were 5.5 and 10.7 months, respectively (13 months in the failure group and 5.7 months for refractory). Grade 3/4 toxicities included neutropenia and thrombocytopenia in 56% and 19% of patients, respectively. Nine patients (12%) experienced neutropenic fever. Grade 3/4 non-hematological toxicities included skin rash (10%), nausea (12%), fatigue (10%) and stomatitis (5%). CONCLUSION: Our trial demonstrates pemetrexed to be active in breast cancer, with manageable toxicity. Activity of pemetrexed did not appear to be adversely affected by prior taxane, 5-fluorouracil or endocrine treatments.

Adult↗
PubMed2002

Phase I safety, pharmacokinetic, and pharmacodynamic trial of ZD1839, a selective oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with five selected solid tumor types.

PURPOSE: To establish the safety and tolerability of ZD1839 (Iressa), a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, and to explore its pharmacokinetic and pharmacodynamic effects in patients with selected solid tumor types. PATIENTS AND METHODS: This was a phase I dose-escalating trial of oral ZD1839 150 mg/d to a maximum of 1,000 mg/d given once daily for at least 28 days. Patients with either advanced non-small-cell lung, ovarian, head and neck, prostate, or colorectal cancer were recruited. RESULTS: Eighty-eight patients received ZD1839 (150 to 1,000 mg/d). At 1,000 mg/d, five of 12 patients experienced dose-limiting toxicity (grade 3 diarrhea [four patients] and grade 3 somnolence [one patient]). The most frequent drug-related adverse events (AEs) were acne-like rash (64%) and diarrhea (47%), which were generally mild (grade 1/2) and reversible on cessation of treatment. No change in ZD1839 safety profile was observed with prolonged administration. Pharmacokinetic analysis showed steady-state exposure to ZD1839 in 98% of patients by day 7. Nineteen patients had stable disease and received ZD1839 for >or= 3 months; seven of these patients remained on study drug for >or= 6 months. Serial skin biopsies taken before treatment and at approximately day 28 revealed changes indicative of inhibition of the EGFR signaling pathway. CONCLUSION: ZD1839 was generally well tolerated, with manageable and reversible AEs at doses up to 600 mg/d and dose-limiting toxicity observed at 1,000 mg/d. ZD1839 treatment resulted in clinically meaningful disease stabilization across a range of tumor types and doses. Pharmacodynamic changes in skin confirmed inhibition of EGFR signaling, which was predicted from the mode of action of ZD1839.

Administration, Oral↗
PubMed2002

A randomised trial of oral versus intravenous topotecan in patients with relapsed epithelial ovarian cancer.

A multicentre, randomised study was carried out in Europe, South Africa and North America to compare the activity and tolerability of oral versus intravenous (i.v.) topotecan in patients with relapsed epithelial ovarian cancer. Patients who had failed first-line therapy after one platinum-based regimen, which could have included a taxane, were randomised to treatment with either oral (p.o.) topotecan, 2.3 mg/m(2)/day or i.v. topotecan 1.5 mg/m(2)/day for 5 days every 21 days. Patients were stratified by prior paclitaxel exposure, interval from previous platinum therapy and tumour diameter. 266 patients were randomised. Response rates were 13% orally (p.o.) and 20% (i.v.) with a complete response in 2 and 4 patients, respectively. The difference in the response rates was not statistically significant. Median survival was 51 weeks (p.o.) and 58 weeks (i.v.) with a risk ratio of death (p.o. to i.v. treatment) of 1.361 (95% confidence interval (CI): 1.001, 1.850). Median time to progression was 13 weeks (p.o.) and 17 weeks (i.v.). The principal toxicity was myelosuppression although grade 3/4 neutropenia occurred less frequently in those receiving oral topotecan. Toxicity was non-cumulative and infectious complications were relatively infrequent. Non-haematological toxicity was generally mild or moderate. The incidence of grade 3/4 gastrointestinal events was slightly higher for oral than i.v. topotecan. Oral topotecan shows activity in second-line ovarian cancer and neutropenia may be less frequent than with the i.v. formulation. A small, but statistically significant, difference in survival favoured the i.v. formulation, but the clinical significance of this needs to be interpreted in the context of second-line palliative treatment. Oral topotecan is convenient and well tolerated and further studies to clarify its role are ongoing.

Administration, Oral↗
PubMed2002

Population pharmacokinetic and dynamic analysis of the topoisomerase I inhibitor lurtotecan in phase II studies.

Population pharmacokinetic-dynamic analysis was prospectively integrated in a broad phase II program of lurtotecan (GI147211), a novel camptothecin derived topoisomerase I inhibitor, to determine the population pharmacokinetic profile in a larger population, to estimate individual pharmacokinetic parameters and to investigate relationships with clinical outcome. A sparse sampling method was applied during course one, which involved two sampling time-points. A Bayesian algorithm was used to estimate individual pharmacokinetic parameters, in particular total plasma clearance (CL) and volume of distribution. In total, samples were collected of 109 (63%) of 173 patients. Pharmacokinetic-dynamic evaluation could be carried out successfully in 85 (78%) of the sampled patients. CL of lurtotecan showed substantial variability (mean 87 +/- 28 L/h) and was of the same magnitude as in the phase I studies where full pharmacokinetic curves were used. Residual variability in the population estimate of CL was 9.9%. No significant relationships were observed between exposure parameters and toxicity nor likelihood of tumor response, however the latter relationship may well have been obscured by the heterogeneity of the studied population. Prospective implementation of large scale population pharmacokinetic-dynamic analysis is feasible and important to establish whether interpatient variability in drug exposure is a major determinant of toxicity or activity.

Adult↗
PubMed2001

Randomized double-blind phase II survival study comparing immunization with the anti-idiotypic monoclonal antibody 105AD7 against placebo in advanced colorectal cancer.

The cancer vaccine 105AD7 is an anti-idiotypic monoclonal antibody that mimics the tumour-associated antigen 791T/gp72 (CD55, Decay Accelerating Factor) on colorectal cancer cells. Phase I studies in patients with advanced disease confirmed that 105AD7 is non-toxic, and that T cell responses could be generated. A prospective, randomized, double-blind, placebo-controlled survival study in patients with advanced colorectal cancer was performed. 162 patients were enrolled between April 1994 and October 1996. Patients attended at trial entry, and at 6 and 12 weeks, where they received 105AD7 or placebo. Study groups were comparable in terms of patient demographics, and time from diagnosis of advanced colorectal cancer (277.1 v 278.6 days). Baseline disease was similar, with 50% of patients having malignancy in at least 2 anatomic sites. Compliance with treatment was poor, with only 50% of patients receiving 3 planned vaccinations. Median survival from randomization date was 124 and 184 days in 105AD7 and placebo arms respectively (P = 0.38), and 456 and 486 days from the date of diagnosis of advanced disease (P = 0.82). 105AD7 vaccination does not prolong survival in patients with advanced colorectal cancer. The reasons for lack of efficacy are unclear, but may reflect the high tumour burden in the patient population, and poor compliance with immunization. Further vaccine studies should concentrate on patients with minimal residual disease.

Adult↗
PubMed2001

Activity of the dolastatin analogue, LU103793, in malignant melanoma.

LU103793, a synthetic analogue of dolastatin 15, showed interesting pre-clinical activity in melanoma xenografts. In this phase II multicentre trial, 80 chemotherapy-naïve patients with metastatic melanoma received a total of 218 cycles of treatment. The response rate showed one complete and three partial responses of median duration six months (range 3-9.1). Toxicity was moderate, mostly haematological (neutropenia grade 4 in 16%, grade 3 in 3%). There were no significant problems with hypertension or other non-haematological toxicities.

Adult↗
PubMed2000

Carzelesin phase II study in advanced breast, ovarian, colorectal, gastric, head and neck cancer, non-Hodgkin's lymphoma and malignant melanoma: a study of the EORTC early clinical studies group (ECSG).

PURPOSE: In a phase II trial, the activity of carzelesin, a cyclopropylpyrroloindole prodrug analog, was assessed. PATIENTS AND METHODS: Carzelesin was used as second- or third-line chemotherapy in patients with breast, ovarian, head and neck cancer and non-Hodgkin's lymphoma, and as first-line chemotherapy in patients with colorectal and gastric cancer and melanoma. The drug was given as a bolus infusion at a 4-weekly dose of 150 microg/m2. A total of 140 patients were entered and a total of 285 courses were administered. RESULTS: In general, the compound was well tolerated. Myelotoxicity was the most common toxicity. Grade 3 and 4 leukopenia was observed in 18.6% of the courses, neutropenia in 20.3%, thrombocytopenia in 16.2% and anemia in 8.7%. Double nadirs were seen in a total of 41 courses for neutrophils, in 40 for leukocytes and in 3 for platelets. Non-hematological toxicity was very mild. Only one partial response in a patient with melanoma was seen. CONCLUSIONS: At this dose and schedule carzelesin did not yield activity in the types of tumors studied.

Adult↗
PubMed2000

Temozolomide and treatment of malignant glioma.

Malignant gliomas (glioblastoma multiforme and anaplastic astrocytoma) occur more frequently than other types of primary central nervous system tumors, having a combined incidence of 5-8/100,000 population. Even with aggressive treatment using surgery, radiation, and chemotherapy, median reported survival is less than 1 year. Temozolomide, a new drug, has shown promise in treating malignant gliomas and other difficult-to-treat tumors. Temozolomide, a p.o. imidazotetrazine second-generation alkylating agent, is the leading compound in a new class of chemotherapeutic agents that enter the cerebrospinal fluid and do not require hepatic metabolism for activation. In vitro, temozolomide has demonstrated schedule-dependent antitumor activity against highly resistant malignancies, including high-grade glioma. In clinical studies, temozolomide consistently demonstrates reproducible linear pharmacokinetics with approximately 100% p.o. bioavailability, noncumulative minimal myelosuppression that is rapidly reversible, and activity against a variety of solid tumors in both children and adults. Preclinical studies have evaluated the combination of temozolomide with other alkylating agents and inhibitors of the DNA repair protein O6-alkylguanine alkyltransferase to overcome resistance to chemotherapy in malignant glioma and malignant metastatic melanoma. Temozolomide has recently been approved in the United States for the treatment of adult patients with refractory anaplastic astrocytoma and, in the European Union, for treatment of glioblastoma multiforme showing progression or recurrence after standard therapy. Predictable bioavailability and minimal toxicity make temozolomide a candidate for a wide range of clinical testing to evaluate the potential of combination treatments in different tumor types. An overview of the mechanism of action of temozolomide and a summary of results from clinical trials in malignant glioma are presented here.

Adult↗
PubMed1997

Multicentre CRC phase II trial of temozolomide in recurrent or progressive high-grade glioma.

PURPOSE: Patients with progressive or recurrent supratentorial high-grade gliomas were entered into a multicentre phase II trial to evaluate the efficacy and toxicity of temozolomide. METHODS: The treatment schedule was 150-200 mg/m2 per day orally for 5 days repeated every 28 days. Response evaluation was by a combination of neurological status evaluation (MRC scale) and imaging. RESULTS: Of 103 eligible patients enrolled, 11 (11%) achieved an objective response and a further 48 (47%) had stable disease. The median response duration was 4.6 months. Response rates were similar for anaplastic astrocytomas (grade III) and glioblastoma multiforme (grade IV) tumours. Predictable myelosuppression was the major toxicity. CONCLUSIONS: The observation of objective responses and tolerable side effects in this heterogeneous population of patients supports the further investigation of this agent in high-grade gliomas.

Adult↗
PubMed1997

Identifying home advantage in international tennis and golf tournaments.

A regression analysis of competitors' tournament results in relation to their world rankings was proposed to identify the effect of home advantage in international 'grand-slam' tennis and 'major' golf tournaments. The results provided little evidence of home advantage in either the grand-slam tennis or the golf tournaments held in 1993. The only possible evidence of home advantage was found in the Wimbledon tennis and the US Open golf championships. Even these findings can be explained, at least partially, by (1) the availability of information concerning the low world rankings of the British tennis players competing at Wimbledon, and (2) selective entry, allowing only the world's top-ranked foreign golfers into the US open golf tournament. In both cases, the lower ranking home competitors have a greater opportunity to perform above their anticipated world rankings. Therefore, provided entry into tennis and golf tournaments is truly 'open' to both the host nation's representatives and foreign competitors alike, home advantage does not appear to be a major factor influencing the competitors' performance in such competitions. These findings may be explained by the relatively objective nature of the scoring systems used in tennis and golf, unlike the subjective influence of refereeing decisions on the results of team-games such as soccer.

Analysis of Variance↗
PubMed1993

Platinum complexes in cancer medicine: pharmacokinetics and pharmacodynamics in relation to toxicity and therapeutic activity.

The study of the pharmacokinetics and pharmacodynamics of platinum based anti-cancer drugs has done much to direct their development, at both preclinical and clinical levels. The clinical development of cisplatin depended on an understanding of its mechanism of action. The amelioration of the renal toxicity of cisplatin with sodium chloride infusion and forced diuresis is thought to rely on a common ion effect to suppress the formation of aquated species in the renal tubule. Studies of the modulation of cisplatin toxicity with other agents have followed, although none has yet achieved widespread acceptance. Following the demonstration of the important clinical role for cisplatin, studies of the relationship between toxicity and the reactivity of the leaving groups led to the development of the less toxic but equally effective analogue, carboplatin. The clinical development of carboplatin has in turn been strongly influenced by the studies of its pharmacokinetics, with pharmacokinetically guided dosing now being standard in many cancer centres and also being widely used in current clinical trials. Pharmacokinetic studies in animals have demonstrated that it is possible to make analogues that have good oral bioavailability. Apart from the convenience of oral administration, there is also the suggestion that these molecules may possess activity against certain cisplatin resistant cell lines. For the future, the development of sensitive methodologies whereby the exact types of platinum-DNA adducts formed can be characterized may allow the reason for the remarkable anti-tumour activity of these complexes to be elucidated and further, more selective compounds to be designed. The history of the development of platinum compounds emphasizes the importance of performing intensive pharmacokinetic, pharmacodynamic and mechanistic studies in concert with the clinical development of any class of agents.

Antineoplastic Agents↗
PubMed1989

EBV. Managing the physiological and psychosocial implications of the Epstein-Barr virus.

EBV has both physiological and psychological implications. Few medical/nursing interventions are available to alleviate the physical stressors and fatigue. The primary nursing intervention, therefore, becomes one of providing emotional support and psychosocial interventions. Providing measures to ensure adequate sleep will assist the patient in more positive feelings about self. Although causation and diagnosis of this syndrome may be debated in the medical literature, the nursing role is to provide support and guidance for these patients. Longitudinal studies could be done to facilitate the understanding of the long-term effects of EBV and the outcome measures of mental health interventions.

Adult↗