Biomedical subjects

J Schueller

Publications and source records attributed to J Schueller.

5 recordsLinked to original sources

PubMed2000

A double-blind, randomised, parallel study comparing intravenous dolasetron plus dexamethasone and intravenous dolasetron alone for the management of fractionated cisplatin-related nausea and vomiting.

Fractionated cisplatin-containing regimens are routinely used for chemotherapy in certain types of cancer. Dolasetron has been shown to be effective in preventing acute emesis related to high-dose cisplatin chemotherapy over 24 h; its effectiveness has not been evaluated in fractionated cisplatin-containing chemotherapy. This trial was designed to assess the efficacy of dolasetron alone or dolasetron plus dexamethasone in preventing nausea and vomiting related to fractionated cisplatin chemotherapy. The patients were 210 cancer in-patients, who were randomised to receive 100 mg dolasetron i.v. or 100 mg dolasetron i.v. plus 20 mg dexamethasone before chemotherapy primarily with cisplatin (15-50 mg/m2) infused over < or =4 h for at least 2 but not more than 5 consecutive days. Dolasetron was administered to all patients 30 min before cisplatin. Dexamethasone was administered in double-blind fashion 5 min before cisplatin. Efficacy was measured at hour 24 of each study day using complete response (no vomiting and no rescue medication) and maximum severity of nausea, self-assessed by patients using a 100mm visual analogue scale. Most (198) of the patients completed the study and were evaluable. Overall complete response rates were significantly higher in the dolasetron plus dexamethasone group than in the dolasetron only group (72.9% vs. 40.8%, respectively; P<0.0001). Complete response rates on each study day were also significantly higher with dolasetron plus dexamethasone than with dolasetron alone (P<0.029), with an attenuated efficacy in the delayed phase in both groups. Chi-square test and logistic regression applied to daily response rates indicated a significant influence of treatment (day 1: P = 0.0002, day 2: P<0.0001, day 3: P = 0.0007, day 4: P = 0.0007, day 5: P = 0.029). Treatment and duration of chemotherapy exerted the only statistically significant subgroup effects on complete response (P<0.0001). Both treatments were administered safely. As seen with other 5-HT3 receptor antagonist antiemetics, the addition of dexamethasone to dolasetron significantly increases effectiveness in preventing nausea and vomiting related to fractionated cisplatin chemotherapy. Both dolasetron and dolasetron plus dexamethasone were well tolerated.

Adult↗

PubMed1998

Phase II trial of dexverapamil and epirubicin in patients with non-responsive metastatic breast cancer.

Agents capable of reversing P-glycoprotein-associated multidrug resistance have usually failed to enhance chemotherapy activity in patients with solid tumours. Based on its toxicity profile and experimental potency, dexverapamil, the R-enantiomer of verapamil, is considered to be promising for clinical use as a chemosensitizer. The purpose of this early phase II trial was to evaluate the effects of dexverapamil on epirubicin toxicity, activity and pharmacokinetics in patients with metastatic breast cancer. A two-stage design was applied. Patients first received epirubicin alone at 120 mg m(-2) i.v. over 15 min, repeated every 21 days. Patients with refractory disease continued to receive epirubicin at the same dose and schedule but supplemented with oral dexverapamil 300 mg every 6 h x 13 doses. The Gehan design was applied to the dexverapamil/epirubicin cohort of patients. Thirty-nine patients were entered on study, 25 proceeded to receive epirubicin plus dexverapamil. Dexverapamil did not increase epirubicin toxicity. The dose intensity of epirubicin was similar when used alone or with dexverapamil. In nine intrapatient comparisons, the area under the plasma concentration-time curve (AUC) of epirubicin was significantly reduced by dexverapamil (mean 2968 vs 1901 microg ml[-1] h[-1], P= 0.02). The mean trough plasma levels of dexverapamil and its major metabolite nor-dexverapamil were 1.2 and 1.5 microM respectively. The addition of dexverapamil to epirubicin induced partial responses in 4 of 23 patients evaluable for tumour response (17%, CI 5-39%, s.e.P 0.079). The remissions lasted 3, 8, 11 and 11+ months. These data suggest that the concept of enhancing chemotherapy activity by adding chemosensitizers may function not only in haematological malignancies but also in selected solid tumours. An increase in the AUC and toxicity of cytotoxic agents does not seem to be a prerequisite for chemosensitizers to enhance anti-tumour activity.

Adult↗

PubMed1981

A new technique for percutaneous nephropyelostomy.

Primary insertion of a large caliber catheter into the renal pelvis would provide the most favorable drainage in all cases in which urinary diversion by nephropyelostomy is indicated. Therefore, the puncture technique of Guenther and associates was modified. A specially designed balloon catheter was used to prevent dislocation.

Drainage↗

PubMedDate not supplied

Disposition of paclitaxel (Taxol) and its metabolites in patients with advanced breast cancer (ABC) when combined with trastuzumab (Hercpetin).

Monoclonal antibodies are capable of modulating drug metabolising enzymes resulting in unexpected plasma concentrations of a drug when given concomitantly. Therefore plasma concentration of paclitaxel (PTX) and its metabolites has been monitored in 10 patients with advanced breast cancer during treatment with PTX alone or combined with trastuzumab (TMAB, paired cross over design). Compared to the MONO regimen PTX peak plasma concentrations were about 25% lower in the TMAB schedule: cmax = 3294 +/- 1174 ng/ml (MONO: 4368 +/- 1887 ng/ml). TMAB also caused lower peak plasma concentration of the main metabolite 6-hydroxy PTX (248 +/- 89 ng/ml) compared to the MONO schedule (194 +/- 82 ng/ml). Cmax of the minor metabolites was distinctly below 100 ng/ml and consequently differed negligible in both schedules. The similar apparent formation rate of the metabolites in both schedules (range from 30 to 50 min) as well as identical tmax values (range 170-190 min) suggested that TMAB had no influence on PTX metabolism. In accordance to plasma concentrations, AUClast of PTX was lower in the MONO schedule (733 +/- 197 microg/ml*min, AUClast = 669 +/- 248 microg/ml*min for TMAB) but without significance. In summary no indices for an altered plasma disposition of PTX and its metabolites could be found when TMAB was given concomitantly.

Adult↗

PubMedDate not supplied

Clinical pharmacokinetics and metabolism of paclitaxel after polychemotherapy with the cytoprotective agent amifostine.

BACKGROUND: Cytoprotection of healthy cells represents a new approach in cancer chemotherapy, but a pharmacokinetic drug interaction between the cytostatic and the cytoprotectant is undesired. METHODS: The purpose was to evaluate the clinical pharmacokinetics (PHK) of paclitaxel (PACLI) and its metabolites under cytoprotection in patients suffering from breast cancer. PACLI was administered alone and in a second cycle in combination with amifostine (AMI) as a paired cross over. RESULTS: In both treatment schedules the steady state of PACLI occurred after 3 hours, the tmax of metabolites between 3 and 4 hours. The mean steady-state concentration was cmax = 5432 +/- 1238 ng/ml in the control group and cmax = 5140 +/- 2407 ng/ml in the AMI group. For the serum metabolites, the findings were very similar: 6-OH-PACLI: cmax 413 +/- 153 ng/ml versus 432 +/- 304 ng/ml, 3"-OH-PACLI: cmax 99 +/- 103 ng/ml versus 123 +/- 98 ng/ml, 3",6-DiOH-PACLI: cmax 43 +/- 55 ng/ml versus 75 +/- 85 ng/ml. AUC values of metabolites were slightly higher in the AMI group, but PHK seemed equal. CONCLUSION: The results gave evidence, that cytoprotection with AMI has no clinical consequences on PACLI pharmacokinetics and biotransformation.

Aged↗