Biomedical subjects

E U Steinhauer

Publications and source records attributed to E U Steinhauer.

7 recordsLinked to original sources

PubMed2003

Efficacy and safety of ibandronate in the treatment of hypercalcemia of malignancy: a randomized multicentric comparison to pamidronate.

GOALS: To compare the efficacy and safety of ibandronate and pamidronate in patients with hypercalcemia of malignancy (HCM). PATIENTS AND METHODS: Seventy-two patients with HCM [albumin-corrected serum calcium (CSC) >2.7 mmol/l] were treated with a single infusion of ibandronate (2 or 4 mg) or pamidronate (15, 30, 60, or 90 mg) on day 0. The dose was dependent on the severity of hypercalcemia (baseline CSC level). CSC was assessed daily until day 4, then at intervals until day 28. The primary endpoint was lowering of CSC at day 4. Secondary endpoints included the number of patients responding and time to re-increase following response. MAIN RESULTS: Using the CSC baseline approach, the most frequently administered doses were 4 mg ibandronate (78.4%) and 60 mg pamidronate (50.0%). Mean lowering of CSC at day 4 was 0.6 mmol/l for ibandronate and 0.41 mmol/l for pamidronate. The 95% confidence interval for the difference ibandronate pamidronate had a lower limit of 0.05 mmol/l, indicating that ibandronate was as effective as pamidronate. The number of patients responding to the two agents was also similar; 76.5% of ibandronate patients and 75.8% of pamidronate patients were rated as responders after the first dose of study medication. The median time to re-increase after response was longer for ibandronate (14 days) than pamidronate (4 days) ( P=0.0303). In the subgroup of 17 patients with high baseline CSC (>3.5 mmol/l), ibandronate appeared to be more effective than pamidronate. The safety profile of both agents was similar. CONCLUSIONS: Ibandronate is at least as effective as pamidronate in the treatment of HCM. Furthermore, in patients with higher baseline CSC ibandronate appears to be more effective than pamidronate. The duration of response is significantly longer with ibandronate than pamidronate.

Administration, Oral↗

PubMed1999

Serum parathyroid hormone-related protein levels and response to bisphosphonate treatment in hypercalcemia of malignancy.

The pathogenesis of hypercalcemia of malignancy comprises increased net bone resorption and enhanced renal tubular reabsorption of calcium (Ca). To evaluate the prevalence of an increased renal tubular reabsorption of Ca index [tubular reabsorption of calcium index (TRCaI)] in cancer patients with hypercalcemia and of elevated circulating levels of PTH-related protein (PTHrP), which is recognized as a major mediator of this syndrome, we investigated 315 well rehydrated patients, aged 58.1 +/- 0.7 yr (mean +/- SEM), with hypercalcemia [albumin-corrected plasma Ca (pCa), >2.7 mmol/L] secondary to histologically proven malignancy. Changes in pCa and, therefore, various Ca filtered loads were obtained by different degrees of bone resorption inhibition achieved with a single infusion of the bisphosphonate ibandronate, given at various doses on a randomized, double blind basis. PTHrP was determined at baseline in 147 of the patients and 7 days after bisphosphonate therapy in 73. Before ibandronate therapy, pCa was 3.36 +/- 0.02 mmol/L, mean TRCaI was increased at 3.09 +/- 0.03 mmol/L glomerular filtration rate (GFR; normal, 2.40-2.90), and 65% of patients had TRCaI above 2.90 mmol/L GFR. Mean serum PTHrP levels were 4.9 +/- 0.5 pmol/L (normal, <2.5) and values above the normal range were found in 53% of the patients (76% in lung and upper respiratory tract malignancies). By 7 days after the infusion of ibandronate, a decrease in pCa of 0.69 +/- 0.03 mmol/L (20.0 +/- 0.7%; P < 0.001) and in bone resorption [mean change in fasting urinary Ca, 0.09 +/- 0.04 mmol/L GFR (47.6 +/- 8.6%; P < 0.001) and 14.4 +/- 1.7 nmol/mmol (27.6 +/- 10.6%; P < 0.01) in deoxypyridinoline] was observed. TRCaI was slightly lowered by 0.30 +/- 0.09 mmol/L GFR. Mean changes in PTHrP, 1,25-dihydroxyvitamin D3, and PTH were +0.7 +/- 0.4 (P = NS), +27.6 +/- 3.0 (P < 0.001), and +2.9 +/- 0.8 (P < 0.005) pmol/L, respectively. After ibandronate treatment, the relative risk of relapsing hypercalcemia was particularly increased (3.43-fold) in lung and upper respiratory tract malignancies. These results obtained in a large cohort of patients indicate a significant prevalence of an increased renal tubular reabsorption of calcium index in hypercalcemia of malignancy and a substantial proportion of patients with detectable PTHrP.

Absorption↗

PubMed1997

Dose-response study of ibandronate in the treatment of cancer-associated hypercalcaemia.

Hypercalcaemia is an important cause of morbidity in malignant disease. We studied the efficacy and safety of intravenous ibandronate (a new, potent bisphosphonate) in a multicentre study of 147 patients with severe cancer-associated hypercalcaemia which had been resistant to treatment with rehydration alone. Of 131 randomized patients who were eligible for evaluation, 45 were allocated to receive 2 mg ibandronate, 44 patients to receive 4 mg and 42 patients to receive 6 mg. Serum calcium values fell progressively in each group from day 2, reaching a nadir at day 5, and in some patients normocalcaemia was maintained for up to 36 days after treatment. The 2-mg dose was significantly less effective than the 4-mg or 6-mg dose in correcting hypercalcaemia, as the number of patients who achieved serum calcium values below 2.7 mM after treatment was 50% in the 2-mg group compared with 75.6% in the 4-mg group and 77.4% in the 6-mg group (P < 0.05; 2 mg vs others). In a logistic regression analysis, three factors were found to predict response; ibandronate dose (higher doses were more effective), severity of presenting hypercalcaemia (severe hypercalcaemia was associated with less complete response) and tumour type (patients with breast carcinoma and haematological tumours responded better than those with other tumours). Ibandronate was generally well tolerated and no serious drug-related adverse events were observed. We conclude that ibandronate is a safe, well tolerated and effective treatment for cancer-associated hypercalcaemia, which should prove a useful addition to the current range of therapies available to treat this condition.

Bone Resorption↗

PubMed1996

Randomized phase II trial comparing different doses of the bisphosphonate ibandronate in the treatment of hypercalcemia of malignancy.

PURPOSE: To evaluate the hypocalcemic effect and safety of three different doses of the bisphosphonate ibandronate in tumor-associated hypercalcemia, and to identify factors predicting response. PATIENTS AND METHODS: One hundred seventy-four cancer patients with a serum calcium level greater than 2.7 mmol/L (10.8 mg/dL) were enrolled onto the trial. If hypercalcemia persisted after fluid repletion, patients were randomly assigned to treatment with 0.6 mg, 1.1 mg, and 2.0 mg of ibandronate. Response, defined as restoration of normocalcemia, was evaluated by an intent-to-treat analysis. RESULTS: One hundred seventy-three (99%) patients were assessable for toxicity and 151 (87%) for efficacy. The administration of 0.6 mg (group A), 1.1 mg (group B), or 2.0 mg (group C) of ibandronate led to response rates of 44%, 52%, and 67%, respectively. Significantly more patients in group C responded than in group A (P = .0276). Of the various parameters examined, only the initial serum calcium level (P < .0001; odds ratio, 0.083) and the dose of ibandronate (P = .0162; odds ratio, 2.094) correlated with response. One hundred ninety-five adverse events (AEs) were reported, 99 classified as serious and 96 as nonserious. Three serious and sixteen nonserious AEs were considered related to ibandronate treatment. The three serious AEs were one case with thrombocytopenia, one with nausea, and one with fever. CONCLUSION: Ibandronate therapy led to a dose-dependent reduction in serum calcium levels. The response to ibandronate treatment correlated negatively with the initial serum calcium level and positively with the dose administered. A dose of 2 mg was necessary to achieve a response rate comparable to that in previous studies with the bisphosphonates pamidronate and clodronate. Because the incidence of drug-associated AEs was low, a dose escalation of ibandronate can be recommended for further clinical trials.

Adult↗

PubMed1990

Sequential versus alternating chemotherapy for high-grade non-Hodgkin's lymphomas: preliminary results of a phase III multicentre trial.

In a multicentre phase III trial 105 previously untreated patients with high-grade non-Hodgkin's lymphomas stage II-IV were randomized to receive either 4 cycles of CHOEP (cyclophosphamide 750 mg/m2 i.v. day 1, doxorubicin 50 mg/m2 i.v. day 1, vincristine 2 mg i.v. day 1, etoposide 100 mg/m2 i.v. days 3-5, prednisolone 100 mg p.o. days 1-5) (treatment arm A), or 4 cycles of chemotherapy with hCHOP (cyclophosphamide 1,200 mg/m2 i.v. day 1, doxorubicin 40 mg/m2 i.v. days 1 + 2, vincristine 2 mg i.v. day 1, prednisolone 100 mg p.o. days 1-5) alternating with IVEP (ifosfamide 1,500 mg/m2 i.v. days 1-5, vindesine 3 mg/m2 i.v. day 1, etoposide 120 mg/m2 i.v. days 3-5, prednisolone 100 mg p.o. days 1-5) in treatment arm B. After 4 cycles of chemotherapy an involved field irradiation with a total dose of 35 Gy was given to all patients demonstrated to be in complete or partial remission without persisting extranodal disease. A complete response (CR) was seen in 86/105 patients (82%) with 88% CR in arm A vs. 76% CR in arm B. During a median follow-up of 11 months (range 2-31 months) 13 patients relapsed (6 patients arm A, 7 patients arm B). The overall survival at 30 months is projected to be 72% vs. 83% for arm A and B respectively. Disease-free survival is projected to be 78% in arm A and 45% in arm B at 28 months. So far, the differences in CR, survival and disease-free survival are not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1985

[Testing of granulocyte function after gravity leukapheresis].

In a laboratory model granulocyte concentrates are produced by a procedure of gravitational leukopheresis. Hydroxyaethyl starch (HAS) served as an accelerator of sedimentation. In a parallel test arrangement a preparation of hydroxyaethyl taken from the industrial production of the GDR and a control preparation (Plasmasteril) was used. The regaining rate of this method amounts to about 70 per cent with 98 per cent of living cells in the concentrates. Vitality, performance of phagocytosis and ability of migration will only reduce to a slight degree during the first 4 hours, after that time, however, they will decrease significantly. There are no essential differences between the results of both preparations.

Adult↗

PubMedDate not supplied

Sequential versus alternating chemotherapy for high grade non-Hodgkin's lymphomas: a randomized multicentre trial.

In a multicentre phase III trial 146 previously untreated patients with high grade non-Hodgkin's lymphomas stage II-IV were randomized to receive either four cycles of CHOEP (cyclophosphamide 750 mg/m2 iv d 1, doxorubicin 50 mg/m2 iv d 1, vincristine 2 mg iv d 1, etoposide 100 mg/m2 iv d 3-5, prednisolone 100 mg po d 1-5) (treatment arm A), or four cycles of chemotherapy with hCHOP (cyclophosphamide 1200 mg/m2 iv d 1, doxorubicin 40 mg/m2 iv d 1 + 2, vincristine 2 mg iv d 1, prednisolone 100 mg po d 1-5) alternating with IVEP (ifosfamide 1500 mg/m2 iv d 1-5, vindesine 3 mg/m2 iv d 1, etoposide 120 mg/m2 iv d 3-5, prednisolone 100 mg po d 1-5) (treatment arm B). After four cycles of chemotherapy an involved field irradiation with a total dose of 35 Gy was given to all patients in complete or partial remission without persisting extranodal disease. A complete response (CR) was seen in 124/146 patients (86 per cent) with 87 per cent CR in arm A versus 83 per cent CR in arm B. During a median follow-up of 17 months (range 2-40) 30 patients relapsed (16 patients arm A, 14 patients arm B). The overall survival at 40 months is projected to be 71 per cent versus 70 per cent for arm A and B, respectively. Disease-free survival is projected to be 68 per cent in arm A and 59 per cent in arm B at 40 months. So far, the differences in CR, survival and disease-free survival are not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗