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Biomedical subjects

S Carrick

Publications and source records attributed to S Carrick.

9 recordsLinked to original sources
PubMed2005

Single agent versus combination chemotherapy for metastatic breast cancer.

BACKGROUND: It is commonly thought that combining chemotherapy agents for treating women with metastatic breast cancer will result in regimens that are more active, offer superior tumour response rates with more time before progression and improve overall survival. However, it is not known whether giving patients more intensive chemotherapy regimens (judged according to some measure eg dose, dose intensity, response rate, or toxicity) results in better health outcomes. One way to investigate the effect of more versus less-intensive chemotherapy is to compare regimens containing a single drug (and hence possibly less active treatment) with regimens containing a greater number of drugs (and hence possibly more active but more toxic), even when adjustments are made to dosages or schedules to account for toxicity. OBJECTIVES: To compare use of single chemotherapy agents with regimens containing a combination of agents for the treatment of metastatic breast cancer. SEARCH STRATEGY: The Specialised Register maintained by the Editorial Base of the Cochrane Breast Cancer Group was searched on 2nd May 2003 using the codes for "advanced breast cancer", "chemotherapy". Details of the search strategy applied by the group to create the register, and the procedure used to code references, are described in the group's module on The Cochrane Library. SELECTION CRITERIA: Randomised trials comparing single agent chemotherapy with combination therapy in women with metastatic breast cancer. DATA COLLECTION AND ANALYSIS: Data were collected from published trials. Studies were assessed for eligibility and quality, and data were extracted by two independent reviewers. Hazard ratios were derived for time-to-event outcomes where possible, and a fixed effect model was used for meta-analysis. Response rates were analysed as dichotomous variables. Toxicity and quality of life data were extracted where present. MAIN RESULTS: Thirty seven eligible trials were identified of which 28 had published time-to-event data. The quality of randomisation was generally not described. Data, based on an estimated 4220 deaths in 5707 women, show a modest advantage for combination chemotherapy regimens compared with single agents with a hazard ratio (HR) for overall survival of 0.88 (95% CI=0.83-0.94, P<0.0001) and no evident heterogeneity. Results are similar if the analysis is limited to trials in women receiving first-line chemotherapy. Combination regimens are favourably associated with time to progression (overall HR of 0.78 (95% CI=0.73-0.83, P<0.00001) and tumour response rates (OR 1.28, CI=1.15-1.42, P<0.00001) although significant heterogeneity was observed (P=0.002 and P<0.00001 respectively). This probably reflects the varying efficacy of the comparator regimens used in the trials. Women receiving combination regimens experienced a higher toxicity level for leukopenia, hair loss and nausea and vomiting compared with those receiving a single agent, which was statistically significant. AUTHORS' CONCLUSIONS: Compared with single-chemotherapy agents, combination regimens show a statistically significant advantage for tumor response and time to progression in women with metastatic breast cancer, a modest improvement in overall survival and significantly worse toxicities.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Platinum containing regimens for metastatic breast cancer.

BACKGROUND: Studies have reported high tumour response rates for platinum-containing regimens in the treatment of women with metastatic breast cancer. OBJECTIVES: To identify and review the evidence from randomised trials comparing platinum-containing chemotherapy regimens with regimens not containing platinum in the management of women with metastatic breast cancer. SEARCH STRATEGY: The specialised register maintained by the editorial base of the Cochrane Breast Cancer Group was searched on 2nd May 2003 using the codes for "advanced breast cancer", "chemotherapy". Details of the search strategy applied to create the register, and the procedure used to code references, are described in the Cochrane Breast Cancer Group module on The Cochrane Library. SELECTION CRITERIA: Randomised trials comparing platinum-containing chemotherapy regimens with regimens not containing platinum in women with metastatic breast cancer. DATA COLLECTION AND ANALYSIS: Studies were assessed for eligibility and quality, and data (from published trials) were extracted by two independent reviewers. Hazard ratios were derived for time-to-event outcomes, where possible, and a fixed effect model was used for meta-analysis. Response rates were analysed as dichotomous variables. Toxicity and quality of life data (not available) were extracted where present. MAIN RESULTS: Thirteen eligible trials were identified, of which 12 had published time-to-event data. The quality of randomisation was generally not described.Data, based on an estimated 987 deaths in 1377 women, was unable to show a statistically significant difference in favour of platinum-containing regimens. The hazard ratio (HR) for overall survival was 1.00 (95% confidence interval (CI) 0.88 to 1.15, p=0.96), with minor heterogeneity. Results were similar when the analysis was limited to trials in women receiving first line chemotherapy. There was no statistically significant difference in favour of platinum-containing regimens for time to progression (overall HR of 1.06 (95% CI 0.95 to 1.19, p=0.31) although there was marked evidence of heterogeneity (p< 0.0001). There was a statistically significant difference in overall response in favour of platinum-containing regimens (OR 1.47; 95% CI 1.23 to 1.76, p=0.0001). However, there was strong statistical evidence of heterogeneity (p < 0.00010) probably reflecting the varying efficacy of the comparator regimens used in the trials. Heterogeneity may also reflect the differences, and difficulties, in assessing response. Women receiving platinum-containing regimens experienced statistically significant greater toxicity levels for leukopenia, hair loss, nausea and vomiting and anaemia compared with those receiving non-platinum regimens. REVIEWERS' CONCLUSIONS: In view of the significant excess toxicity, lack of progression or survival benefit and the availability of less toxic active agents it is difficult to justify the use of platinum-containing regimens, particularly as first line treatment for women with metastatic breast cancer in routine clinical practice. Ongoing trials are examining the possibility of synergy between platins and trastuzamab, a monoclonal antibody treatment. No randomised trials containing oxalplatin were identified for the present review.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Platinum containing regimens for metastatic breast cancer.

BACKGROUND: Studies have reported high tumour response rates for platinum-containing regimens in the treatment of women with metastatic breast cancer. OBJECTIVES: To identify and review the evidence from randomised trials comparing platinum-containing chemotherapy regimens with regimens not containing platinum in the management of women with metastatic breast cancer. SEARCH STRATEGY: The specialised register maintained by the editorial base of the Cochrane Breast Cancer Group was searched on 2nd May 2003 using the codes for "advanced breast cancer", "chemotherapy". Details of the search strategy applied to create the register, and the procedure used to code references, are described in the Cochrane Breast Cancer Group module on The Cochrane Library. SELECTION CRITERIA: Randomised trials comparing platinum-containing chemotherapy regimens with regimens not containing platinum in women with metastatic breast cancer. DATA COLLECTION AND ANALYSIS: Studies were assessed for eligibility and quality, and data (from published trials) were extracted by two independent reviewers. Hazard ratios were derived for time-to-event outcomes, where possible, and a fixed effect model was used for meta-analysis. Response rates were analysed as dichotomous variables. Toxicity and quality of life data (not available) were extracted where present. MAIN RESULTS: Thirteen eligible trials were identified, of which 12 had published time-to-event data. The quality of randomisation was generally not described.Data, based on an estimated 987 deaths in 1377 women, was unable to show a statistically significant difference in favour of platinum-containing regimens. The hazard ratio (HR) for overall survival was 1.00 (95% confidence interval (CI) 0.88 to 1.15, p=0.96), with minor heterogeneity. Results were similar when the analysis was limited to trials in women receiving first line chemotherapy. There was no statistically significant difference in favour of platinum-containing regimens for time to progression (overall HR of 1.06 (95% CI 0.95 to 1.19, p=0.31) although there was marked evidence of heterogeneity (p< 0.0001). There was a statistically significant difference in overall response in favour of platinum-containing regimens (OR 1.47; 95% CI 1.23 to 1.76, p=0.0001). However, there was strong statistical evidence of heterogeneity (p < 0.00010) probably reflecting the varying efficacy of the comparator regimens used in the trials. Heterogeneity may also reflect the differences, and difficulties, in assessing response. Women receiving platinum-containing regimens experienced statistically significant greater toxicity levels for leukopenia, hair loss, nausea and vomiting and anaemia compared with those receiving non-platinum regimens. REVIEWERS' CONCLUSIONS: In view of the significant excess toxicity, lack of progression or survival benefit and the availability of less toxic active agents it is difficult to justify the use of platinum-containing regimens, particularly as first line treatment for women with metastatic breast cancer in routine clinical practice. Ongoing trials are examining the possibility of synergy between platins and trastuzamab, a monoclonal antibody treatment. No randomised trials containing oxalplatin were identified for the present review.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Consulting about priorities for the NHMRC National Breast Cancer Centre: how good is the nominal group technique.

The National Health and Medical Research Council National Breast Cancer Centre was established to improve outcomes for women by reviewing the literature, developing best practice guidelines and resources and developing a national monitoring system. Its broad terms of reference meant that it was important at the outset to identify priorities for action. The Centre used a national consultative process based on nominal groups to identify priorities. Thirteen consultative workshops were held with over 300 participants including women diagnosed with breast cancer, some of their families and health professionals. There was a high level of agreement between workshops in priorities identified, indicating that the nominal group process results in reliable data. A sub-sample of participants surveyed after the workshops reported being highly satisfied with their participation in the process. The findings indicate that the nominal group process can be useful in selecting priorities for action in health.

Academies and Institutes↗
PubMed1991

Pituitary and plasma arginine vasotocin levels in teleost fish.

The role of arginine vasotocin (AVT) in teleostean osmoregulation is unclear. Its administration may produce dose-dependent effects on renal fluid loss though the physiological significance of such effects is unknown due to the paucity of data on the normal range in pituitary and plasma AVT levels. The present study addresses these questions by examining the pituitary AVT activity in the flounder and plasma AVT concentrations in the flounder, trout, and carp following alterations in environmental tonicity. Flounder pituitary AVT content, measured by bioassay, was elevated in freshwater (FW)-acclimated compared to seawater (SW)-acclimated fish and rapidly fell or rose, respectively, following transfer from FW to SW or from SW to FW to attain a new steady state. Plasma levels of AVT were higher in FW than in SW in both flounder and trout and it would, therefore, appear that the synthesis, storage, and secretion of AVT may be enhanced in FW. In the stenohaline carp plasma levels of AVT were unchanged on acclimation from FW to 40% SW. In SW flounder there was a significant positive correlation between plasma osmolality and plasma AVT concentration. Such a relationship was not apparent in FW fish, which may reflect differing roles for the hormone in these two extremes of osmotic environment.

Animals↗
PubMed1985

Endogenous renin-angiotensin system and drinking behavior in flounder.

High rates of drinking in seawater-adapted, compared with freshwater (FW)-adapted, flounder were associated with raised plasma chloride and osmotic concentrations. Hypotension in FW-adapted fish, after papaverine administration, gave rise to greatly elevated rates of drinking. This dipsogenic response apparently relied on activation of the endogenous renin-angiotensin system (RAS) and was abolished by simultaneous administration of the converting enzyme inhibitor, captopril. Exogenous angiotensin II was shown to be dipsogenic and vasopressor in the FW-adapted fish. The physiological importance of the activation of the RAS in the control of drinking behavior in euryhaline fish is discussed.

Animals↗
PubMed1983

The renin-angiotensin system and drinking in the euryhaline flounder, Platichthys flesus.

Drinking behaviour and its possible regulation by the renin-angiotensin system (RAS) has been examined in the euryhaline flounder. Fluid intake was greater in seawater (SW)-adapted than freshwater (FW)-adapted fish, the latter having significantly lower plasma sodium, chloride, and osmotic concentrations. Oesophageal cannulation in SW-adapted fish resulted in further elevation of drinking rates, which increased proportionally with progressive body water loss as measured by the fall in body weight and rise in plasma tonicity. The influence of the RAS on drinking in SW-adapted fish was examined in animals with an intact gastrointestinal tract. Fluid intake fell markedly following administration of the converting enzyme inhibitor, Captopril. Infusions of angiotensin I (AI) and angiotensin II (AII) induced dose-related increments in the rate of drinking. The increased drinking in response to AI was inhibited, however, by the simultaneous administration of Captopril. The results are consistent with the presence in the flounder of the major elements of the RAS, including AI, AII, and a converting enzyme-like substance. The RAS appears to play an important regulatory role in the adaptative drinking behaviour associated with migration of euryhaline teleosts between FW and SW.

Adaptation, Physiological↗
PubMedDate not supplied

Auto-anti-A1: another cause of ABO discrepancy.

Anti-A1 was found in the serum of a patient of blood group A1 who had never received a blood transfusion. The patient's serum caused agglutination of his own red blood cells. The anti-A1 could be totally absorbed by red blood cells from the patient and from other A1 individuals. The anti-A1 was inhibitable by soluble group A-specific substance and was denatured by 2-mercaptoethanol. The A and H serum transferases were normal. The presence of auto-anti-A1 in the serum of an A1 individual is yet another cause of ABO discrepancy.

ABO Blood-Group System↗