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Biomedical subjects

B Schneeweiss

Publications and source records attributed to B Schneeweiss.

At least 19 recordsLinked to original sources
PubMed2005

Side effects during chemotherapy predict tumour response in advanced colorectal cancer.

To investigate whether a relationship between chemotherapy-associated adverse events and treatment efficacy exists, we have analysed the toxicity, objective response and survival data of 303 patients with advanced colorectal cancer. Patients were divided into two groups: the first with beneficial effect (I, n = 245), and the second with progressive disease (II, n = 58). Differences in terms of incidence rates, type and severity of ad verse events were analysed with univariate and multivariate models. The median number of side effects in group I was 6 vs 4 in group II (OR=1.342; P= 0.0001). An inverse correlation between disease control and treatment tolerance was confirmed when side effects were analysed according to severity and type of treatment-associated toxicities (haematological: P = 0.0005 vs nonhaematological P = 0.0001). When median survival was analysed according to the number of adverse events, it was 10 (95% CI, 3-7), 16 (14-18), and 18 (16-20) months in case of 0-1, 2-5, and > or =6 adverse events, respectively (P = 0.01). In conclusion, the results of this analysis suggest that occurrence of side effects during chemotherapy in advanced colorectal cancer is an independent and reliable prognostic indicator for response and survival.

Adult↗
PubMed2004

Changes of serum chloride and metabolic acid-base state in critical illness.

Alterations of electrolytes and albumin cause metabolic acid-base disorders. It is unclear, however, to what degree these plasma components affect the overall metabolic acid-base state in the course of critical illness. We performed serial analyses of the metabolic acid-base state in 30 critically ill patients over the course of 1 week. We applied a physical-chemical acid-base model and used a linear regression model to determine the influence of sodium, chloride, unmeasured anions and albumin on the net metabolic acid-base state. Progressive hypochloraemia was identified as the main cause of developing metabolic alkalosis. Changes in serum chloride and unmeasured anions were responsible for changes of 41% and 22% in the metabolic acid-base state, respectively. Sodium and albumin played a minor role. In conclusion, chloride is the major determinant of metabolic acid-base state in critical illness.

Acid-Base Imbalance↗
PubMed2003

Irinotecan plus raltitrexed vs raltitrexed alone in patients with gemcitabine-pretreated advanced pancreatic adenocarcinoma.

There is no established second-line treatment for advanced pancreatic cancer after gemcitabine failure. In view of the urgent need for such therapy, and since preclinical and phase I clinical data suggest an encouraging, potentially synergistic activity between raltitrexed and irinotecan, the present randomised phase II study was initiated. A total of 38 patients with metastatic pancreatic adenocarcinoma, who progressed while receiving or within 6 months after discontinuation of palliative first-line chemotherapy with gemcitabine, were enrolled in this study. They were randomised to 3-weekly courses of raltitrexed 3 mg x m(-2) on day 1 (arm A) or irinotecan 200 mg x m(-2) on day 1 plus raltitrexed 3 mg x m(-2) on day 2 (arm B). The primary study end point was objective response, secondary end points included progression-free survival (PFS) and overall survival (OS), as well as clinical benefit response in symptomatic patients (n=28). In the combination arm, the IRC-confirmed objective response rate was 16% (three out of 19 patients had a partial remission; 95% CI, 3-40%), which was clearly superior to that in the comparator/control arm with raltitrexed alone, in which no response was obtained. Therefore, the trial was already stopped at the first stage of accrual. Also, the secondary study end points, median PFS (2.5 vs 4.0 months), OS (4.3 vs 6.5 months), and clinical benefit response (8 vs 29%) were superior in the combination arm. The objective and subjective benefits of raltitrexed+irinotecan were not negated by severe, clinically relevant treatment-related toxicities: gastrointestinal symptoms (42 vs 68%), partial alopecia (0 vs 42%), and cholinergic syndrome (0 vs 21%) were more commonly noted in arm B; however, grade 3 adverse events occurred in only three patients in both treatment groups. Our data indicate that combined raltitrexed+irinotecan seems to be an effective salvage regimen in patients with gemcitabine-pretreated pancreatic cancer. The superior response activity, PFS and OS (when compared to raltitrexed), as well as its tolerability and ease of administration suggest that future trials with this combination are warranted.

Adenocarcinoma↗
PubMed2003

Biweekly high-dose gemcitabine alone or in combination with capecitabine in patients with metastatic pancreatic adenocarcinoma: a randomized phase II trial.

BACKGROUND: Gemcitabine is an active antitumor agent in the treatment of advanced pancreatic cancer, and has shown potential synergistic activity with the oral fluoropyrimidine capecitabine in previous phase I/II trials. Based on this background and in order to define the therapeutic potential and tolerance of this combination more precisely, the present randomized multicenter phase II trial was initiated. PATIENTS AND METHODS: We prospectively randomized 83 patients to treatment with biweekly gemcitabine 2,200 mg/m(2) given as a 30 min intravenous infusion on day 1, or the same treatment plus oral capecitabine 2,500 mg/m(2) given from days 1 to 7. In both arms, chemotherapy was administered for a duration of 6 months unless there was prior evidence of progressive disease. The efficacy of the two treatment arms was evaluated according to standard criteria, i.e. objective response, progression-free survival (PFS) and overall survival (OS), as well as by analysis of clinical benefit response. RESULTS: The overall objective response rate among the 42 patients treated with gemcitabine alone was 14% compared with 7/41 (17%) among those treated with the combination arm. Similar to response rates, there was no apparent difference between the two groups in terms of median PFS (4.0 versus 5.1 months) and median OS (8.2 versus 9.5 months) in the gemcitabine and combination arm, respectively. Of 61 patients with tumor-related symptoms, who were considered evaluable for clinical benefit response, 10/30 (33%) and 15/31 (48.4%) experienced significant palliation in the gemcitabine and combination arm, respectively. Chemotherapy was well tolerated in both arms with only four versus six patients experiencing WHO grade 3 symptoms. Apart from the occurrence of hand-foot syndrome in 10 patients, no major increase in incidence and/or degree of adverse reactions was noted in the combination arm. CONCLUSIONS: Results of this trial suggest a fairly good therapeutic index for the combination of biweekly high-dose gemcitabine and capecitabine for the treatment of advanced pancreatic cancer. Despite a somewhat superior clinical benefit response rate, no advantage over single-agent gemcitabine, however, was noted in terms of objective efficacy parameters.

Adenocarcinoma↗
PubMed2002

Effective combination chemotherapy with paclitaxel and cisplatin with or without human granulocyte colony-stimulating factor and/or erythropoietin in patients with advanced gastric cancer.

A phase II trial was performed to determine the antitumour efficacy and tolerance of combined paclitaxel and cisplatin with or without hematopoetic growth factor support in patients with advanced gastric cancer. Forty-five patients with histologically confirmed metastatic gastric cancer were entered in this trial. Treatment consisted of 2-weekly courses of paclitaxel 160 mg per m2 and cisplatin 60 mg per m2 both given on day 1. Depending on absolute neutrophil counts on the days of scheduled chemotherapeutic drug administration (1000-2000 per microl), a 5-day course of human granulocyte colony-stimulating factor 5 microg x kg(-1) per day was given subcutaneously; in addition, if haemoglobin was <12.0 mg dl(-1), erythropoietin 10 000 IU was administered subcutaneously three times per week. The confirmed overall response rate (intent-to-treat) was 44%, including five complete (11%) and 15 partial remissions (33%). Twelve patients had stable disease (27%), 11 (24%) progressed while on chemotherapy, and two patients were not evaluable. The median time to response was 3 months, the median time to progression 7.0 months, and the median survival time was 11.2 months with 12 patients currently alive. Haematologic toxicity was common, though WHO grade 4 neutropenia occurred in only five patients (11%). Apart from total alopecia in 16 patients (36%), severe non-haematologic adverse reactions included grade 3 peripheral neuropathy in six (13%) and anaphylaxis in two patients. In addition, there was one patient each who experienced grade 3 emesis, diarrhea, and infection, respectively. Our data suggest that the combination of paclitaxel and cisplatin with or without G-CSF and/or erythropoietin has promising therapeutic activity in patients with advanced gastric cancer.

Adenocarcinoma↗
PubMed2002

Second-Line Treatment of Advanced Colorectal Cancer with a Biweekly Oxaliplatin plus Irinotecan Combination Regimen.

BACKGROUND: Both oxaliplatin and irinotecan have demonstrated antitumor activity in pretreated colorectal cancer; experimental and early clinical data suggest that these two drugs may act synergistically. The aim of this study was to document the therapeutic index of a biweekly combination regimen in patients with metastatic colorectal cancer failing prior palliative first-line chemotherapy with raltitrexed. PATIENTS AND METHODS: In this study 27 patients with metastatic colorectal cancer were analyzed, who progressed while on or within 6 months after discontinuation of palliative first-line chemotherapy with raltitrexed. They received oxaliplatin 85 mg/m(2) and irinotecan 150 mg/m(2) both given on days 1 and 15 every 4 weeks. RESULTS: The confirmed overall response rate was 37% (95% confidence interval, 19.4-57.7%), including 2 complete and 8 partial remissions. 12 additional patients (44.4%) had stable disease, and in only 5 cases (18.5%) disease progression was not influenced by chemotherapy. The median progression-free survival for all 27 patients was 8 months (range, 1-16+ months), and 16 patients (59%) are still alive after a median follow-up time of 12.5 months. Hematologic adverse reactions, specifically leukocytopenia and neutropenia, were common though generally mild to moderate with grade 4 toxicity occurring in only 2 cases. The most frequent non-hematologic adverse events included gastrointestinal symptoms; severe nausea/emesis and diarrhea, however, were noted in only 2 and 3 patients, respectively. CONCLUSIONS: Our data suggest that the described biweekly combination regimen of oxaliplatin and irinotecan has substantial antitumor activity in patients with progressive, raltitrexed-pretreated metastatic colorectal cancer. Because of its favorable toxicity profile, further evaluation of this combination seems warranted.

Adult↗
PubMed2001

Energy and substrate metabolism in patients with chronic extensive graft-versus-host disease.

BACKGROUND: Allogeneic stem cell transplantation is frequently complicated by graft-versus-host disease (GVHD). Weight loss is one of the characteristic features of GVHD. The etiology of weight loss in GVHD is not completely understood. METHODS: We measured resting energy expenditure (REE) and substrate oxidation rates by indirect calorimetry in patients with stable chronic extensive GVHD under immunosuppressive therapy (n=13) and sex-, age-, height-, and weight-matched healthy controls (n=13) in order to evaluate metabolic changes in these patients. Measurements were done on day 518+/-261 after allogeneic stem cell transplantation in the postabsorptive state. Serum concentrations of glucagon, norepinephrine, tumor necrosis factor-alpha, interleukin-6, and free fatty acids were determined. RESULTS: Patients showed a maximum weight loss of 22% during their course of GVHD; nevertheless, they regained 15% of total body weight (TBW) during successful treatment of GVHD. Indirect calorimetry showed an increase in REE per kilogram of TBW (patients, 21.8+/-3.1 kcal/kg TBW/day; controls, 19.9+/-2 kcal/kg TBW/day; P<0.05). Respiratory quotient (patients, 0.79+/-0.04, controls, 0.86+/-0.04; P<0.005) and non-protein respiratory quotient (0.78+/-0.05 and 0.87+/-0.05, respectively; P<0.005) were decreased in patients. GVHD patients had elevated serum glucagon and norepinephrine concentrations, whereas tumor necrosis factor-alpha and interleukin-6 were in the normal range. CONCLUSIONS: Patients with chronic extensive GVHD show an increase in REE and alterations in fat and carbohydrate oxidation rates. These changes seem to be the result of increased action of glucagon and norepinephrine.

Adult↗
PubMed2001

Treatment of advanced breast cancer with vinorelbine and docetaxel with or without human granulocyte colony-stimulating factor.

PURPOSE: A multicenter phase II trial was performed to investigate the efficacy and tolerance of docetaxel, vinorelbine with or without recombinant human granulocyte colony-stimulating factor (G-CSF) in patients with metastatic breast cancer. PATIENTS AND METHODS: Between February 1998 and March 1999, 57 patients participated in this trial. Forty-two patients received this combination as first-line and 15 patients as second-line chemotherapy, including 10 patients who had failed anthracyclines. Therapy consisted of vinorelbine 30 mg/m(2) on days 1 and 15 and docetaxel 30 mg/m(2) on days 1, 8, and 15 every 4 weeks. Depending on the absolute neutrophil counts on the day of scheduled chemotherapeutic drug administration, a 5-day course of G-CSF 5 microg/kg/d was given. RESULTS: The overall response rate was 64.3% (95% confidence interval, 48.1% to 78.4%) in patients receiving docetaxel plus vinorelbine as first-line chemotherapy, including eight complete (19%) and 19 partial remissions (45.3%); 11 patients (26.2%) had disease stabilization, and only four (9.5%) progressed. Second-line treatment with this regimen resulted in eight (53.3%) of 15 objective responses, four had stable disease, and three had progressive disease. The median time to progression was 12 months in the first-line and 9.8 months in the second-line setting, respectively. After a median follow-up time of 18 months, 38 patients (65%) were still alive with metastatic disease. Myelosuppression was commonly observed; World Health Organization grade 3 or 4 neutropenia both occurred in 18 patients (32%) and was complicated by septicemia in four cases; grade 3 or 4 thrombocytopenia was seen in two patients (4%), and grade 3 anemia was seen in only one patient (2%). Severe (grade 3) nonhematologic toxicity, except for alopecia, was rarely observed and included nausea/vomiting in two patients (4%), and stomatitis, peripheral neuropathy, and skin toxicity each in one patient. CONCLUSION: Our data suggest that docetaxel and vinorelbine with or without G-CSF is an effective and fairly well tolerated regimen for the treatment of advanced breast cancer. It might be particularly useful in patients previously exposed to adjuvant or palliative anthracyclines and/or alkylating agents.

Adult↗
PubMed2001

Phase II trial of two-weekly gemcitabine in patients with advanced biliary tract cancer.

BACKGROUND: Patients with advanced biliary tract carcinoma face a dismal prognosis as no effective palliative therapy has been defined. The aim of the present phase II investigation was to evaluate the therapeutic efficacy and tolerance of a two-weekly high-dose gemcitabine regimen in this patient population. PATIENTS AND METHODS: Thirty-two consecutive patients with locally unresectable or metastatic biliary tract cancer were enrolled in this multicenter phase II trial. Treatment consisted of gemcitabine 2200 mg/m2 given as a 30-min intravenous infusion every two weeks for a duration of six months unless there was prior evidence of progressive disease. RESULTS: After a median number of 12 treatment courses, 7 of 32 (22%) patients had a partial response that lasted for a median duration of 6.0 months (range 3.5-10.0). Fourteen additional patients (44%) had stable disease, whereas eleven patients (34%) progressed despite therapy. The median time to progression was 5.6 months (range 1.8-13.0); median survival time was 11.5 months (range 3.0-24.0), and the probability of surviving beyond 12 months was 44%. The tolerance of treatment was remarkable with only two patients each experiencing grade 3 leukocytopenia, granulocytopenia and/or thrombocytopenia, and one patient had grade 3 anaemia. Similarly, nonhaematologic side effects were infrequent, and generally mild to moderate. CONCLUSIONS: Two-weekly high-dose gemcitabine seems to represent a potentially effective, safe and well-tolerated regimen for the palliative treatment of patients with advanced biliary tract cancer.

Adult↗
PubMed2001

Second-line treatment with oxaliplatin + raltitrexed in patients with advanced colorectal cancer failing fluoropyrimidine/leucovorin-based chemotherapy.

BACKGROUND: To evaluate the efficacy and tolerance of combined raltitrexed and oxaliplatin in patients with advanced colorectal cancer pretreated with fluoropyrimidine leucovorin-based chemotherapy. PATIENTS AND METHODS: Thirty-six patients with metastatic colorectal cancer, who progressed while receiving or within six months after withholding palliative chemotherapy with fluoropyrimidines leucovorin +/- irinotecan, participated in this study. Treatment consisted of oxaliplatin 130 mg/m2 and raltitrexed 3.0 mg/m2 both given on day 1 every three weeks for a total of eight courses unless prior evidence of progressive disease. RESULTS: The overall objective response rate was 33.3% for all 36 evaluable patients (95% confidence interval (CI): 18.6%-51%). Seventeen additional patients (47.2%) had stable disease, and only seven (19.5%) progressed. The median progression-free survival was 6.5 months (range 1.2-14.0). After a median follow-up time of 12 months, 23 patients (63.8%) are still alive. The tolerance of treatment was acceptable with only 8 of 36 patients (22%) experiencing grade 3 or 4 neutropenia. Grade 3 non-haematological adverse reactions included peripheral sensory neuropathy in three, asthenia in one, diarrhea in two, and clinically insignificant increase in serum transaminases in two patients, respectively. CONCLUSIONS: Our data suggest that the combination of oxaliplatin and raltitrexed has substantial antitumour activity in patients with progressive fluoropyrimidine leucovorin + irinotecan pretreated colorectal cancer. Because of its favorable toxicity profile and convenient three-weekly outpatient administration schedule, further evaluation of this regimen seems warranted.

Adult↗
PubMed2001

Similar metabolic responses to standardized total parenteral nutrition of septic and nonseptic critically ill patients.

BACKGROUND: Nutritional support is an important link between the response to injury and recovery in critical illness. OBJECTIVE: Our goal was to evaluate energy and substrate metabolism in septic and nonseptic critically ill patients in the resting state and during the administration of standardized total parenteral nutrition. DESIGN: This was a prospective, clinical cohort study of 25 consecutively admitted critically ill patients either with (n = 14) or without (n = 11) sepsis who received total parenteral nutrition. Resting energy expenditure was measured on days 0, 2, and 7 by indirect calorimetry. Energy and substrate balances were calculated on days 2 and 7. RESULTS: Resting energy expenditure was not significantly different between septic and nonseptic patients on day 0 (2.65 +/- 0.49 and 2.36 +/- 0.56 kJ x min(-1) x m(-2), respectively). Energy balances were positive for both groups on days 2 (0.68 +/- 0.4 and 0.74 +/- 0.6 kJ x min(-1) x m(-2), respectively; NS) and 7 (0.65 +/- 0.3 and 0.78 +/- 0.5 kJ x min(-1) x m(-2), respectively; NS). Substrate balances were not significantly different between groups on days 0, 2, and 7. Resting energy expenditure on day 0 was negatively correlated with the severity of illness in septic patients only (r = -0.58, P < 0.05). CONCLUSIONS: Metabolic changes were not significantly different between septic and nonseptic critically ill patients during the administration of standardized total parenteral nutrition. A disease-specific macronutrient composition of total parenteral nutrition formulas does not seem to be necessary in either septic or nonseptic critically ill patients.

Basal Metabolism↗
PubMed2000

Treatment of patients with advanced nonsmall cell lung carcinoma using docetaxel and gemcitabine plus granulocyte-colony stimulating factor.

BACKGROUND: A combination regimen comprised of docetaxel, gemcitabine, and granulocyte-colony stimulating factor (G-CSF) was studied in patients with advanced nonsmall cell lung carcinoma (NSCLC) to determine its antitumor efficacy and tolerance. METHODS: Thirty-four patients with advanced measurable NSCLC (3 patients with Stage IIIB and 31 patients with Stage IV disease) were treated with an intravenous combination chemotherapy regimen comprised of docetaxel, 80 mg/m(2), on Day 1 and gemcitabine, 1000 mg/m(2), on Days 1 and 10; G-CSF, 5 microg/kg, was administered subcutaneously between Days 2 and 8. Treatment cycles were repeated every 3 weeks. All patients were evaluable for toxicity and response assessment. A total of 163 courses was administered. RESULTS: Objective tumor response was noted in 17 patients (50%; 95% confidence interval, 32. 5-67.5%), including 2 complete responses (6%) and 15 partial responses (44%). There was no change in 10 patients (29%) and 7 patients developed progressive disease. The median duration of response was 6.5 months (range, 3-15 months) and the median time to disease progression for all patients was 6.8 months (range, 1.8-18 months). The median overall survival time was 13.0 months (range, 2. 5-23+ months) with a 1-year survival rate of 55.8%. Myelosuppression was the most frequently encountered adverse reaction, although World Health Organization Grade 3 or 4 leukocytopenia and/or granulocytopenia occurred in only 18% and 24% of patients, respectively. Other toxicities generally were mild to moderate, and always fully reversible. CONCLUSIONS: With a response rate of 50% and a median survival time of 13 months, the drug combination described in the current study appears to have significant activity against advanced metastatic NSCLC. Due to its fairly good tolerance and ease of administration, further investigation of this regimen appears warranted.

Adult↗
PubMed2000

A phase II trial of biweekly high dose gemcitabine for patients with metastatic pancreatic adenocarcinoma.

BACKGROUND: Although the novel cytidine analog gemcitabine has shown superior antitumor activity compared with weekly bolus 5-fluorouracil in patients with advanced pancreatic carcinoma, further improvements of therapeutic results are warranted. The current Phase II study was initiated to investigate whether this might be achieved by dose intensification. METHODS: Between August 1997 and September 1998, 43 consecutive patients with metastatic pancreatic adenocarcinoma were enrolled in this multicenter Phase II trial. Patients received 4 weekly courses of gemcitabine 2200 mg/m((2)) given as intravenous infusion during 30 minutes on Days 1 and 15 for a duration of 6 months unless there was prior evidence of progressive disease. The efficacy of treatment was assessed according to standard criteria, i.e., objective response, progression free survival, and overall survival, as well as by analysis of clinical benefit response (defined as >/= 50% reduction in pain intensity, >/= 50% reduction in daily analgesic consumption, and/or >/= 20 point improvement in Karnofsky performance status that was sustained for >/= 4 consecutive weeks). RESULTS: Of 43 patients evaluable for objective response, 1 achieved complete and 8 partial remissions, for an overall response rate of 21% (95% confidence interval, 10-36%); 18 additional patients (42%) had stable and 16 (37%) progressive disease. The median time to progression was 5.3 months. Median survival was 8.8 months, and the probability of surviving beyond 12 months was 26.3%. Of 36 patients with tumor-related symptoms who were considered evaluable for clinical benefit response, 16 (44%) experienced significant palliation. The median time to achieve a clinical benefit response was 6 weeks, and its median duration was 27 weeks. Chemotherapy was well tolerated, with leukopenia/granulocytopenia representing the most common side effect. Gastrointestinal and other subjective toxicities were infrequent and generally mild. CONCLUSIONS: Biweekly high dose gemcitabine seems to represent a safe, tolerable, and effective regimen for the palliative treatment of patients with advanced pancreatic carcinoma.

Adenocarcinoma↗
PubMed2000

Resting energy expenditure in short-term starvation is increased as a result of an increase in serum norepinephrine.

BACKGROUND: The effects of food restriction on energy metabolism have been under investigation for more than a century. Data obtained are conflicting and research has failed to provide conclusive results. OBJECTIVE: The objective of this study was to test the hypothesis that in lean subjects under normal living conditions, short-term starvation leads to an increase in serum concentrations of catecholamines and thus to an increase in resting energy expenditure. DESIGN: Resting energy expenditure, measured by indirect calorimetry, and hormone and substrate concentrations were measured in 11 healthy, lean subjects on days 1, 2, 3, and 4 of an 84-h starvation period. RESULTS: Resting energy expenditure increased significantly from 3.97 +/- 0.9 kJ/min on day 1 to 4.53 +/- 0.9 kJ/min on day 3 (P < 0.05). The increase in resting energy expenditure was associated with an increase in the norepinephrine concentration from 1716. +/- 574 pmol/L on day 1 to 3728 +/- 1636 pmol/L on day 4 (P < 0.05). Serum glucose decreased from 4.9 +/- 0.5 to 3.5 +/- 0.5 mmol/L (P < 0.05), whereas insulin did not change significantly. CONCLUSIONS: Resting energy expenditure increases in early starvation, accompanied by an increase in plasma norepinephrine. This increase in norepinephrine seems to be due to a decline in serum glucose and may be the initial signal for metabolic changes in early starvation.

3-Hydroxybutyric Acid↗