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Biomedical subjects

J Schüller

Publications and source records attributed to J Schüller.

At least 55 records · Page 3Linked to original sources

[Pharmacokinetic aspects of dosage increase of recombinant interferon alpha-2B in patients following intraperitoneal and intra-arterial application].

Interferon-alpha-2 b (IFN) was administered as an i.a. bolus at doses of 3 and 5 million international units (MIU), as an i.a. 24h long-time infusion at 3 and 5 MIU and as an i.p. 90 min short-time infusion at 5, 10 and 15 MIU. Dose escalation of IFN on i.p. administration leads to correspondingly elevated AUC values of IFN (correlating to the dose) in the peritoneal fluid (PF) and blood, with a shift of the steady-state at about 2h. Bioavailability of IFN is 30 times higher for PF than for blood. t1/2 el, Vd and total clearance are not influenced by dose escalation in both compartments due to their dose-independency. IFN is eliminated from the PF with t1/2 el = 10-32h and from the blood with t1/2 el = 5-13h. After an i.a. bolus at either dosage IFN is distributed from the blood with a half-life of below 2h. 24h infusion leads to a steady-state within 4-6h and a cmax of 8.5 or 12.5 units/ml, respectively. IFN is slowly eliminated during infusion with a t1/2 el of 16h.

Dose-Response Relationship, Drug↗

[Status and trends in locoregional chemotherapy].

The idea to increase the cytostatic concentration by direct perfusion of the target organ and to simultaneously reduce the systemic side effect is almost 40 years old. New techniques brought new impulses to this old method, namely regional chemotherapy, by the discovery of a fully implantable catheter system as a byproduct of space research. This system can be used intravenously, intraarterially and intraperitoneally. In addition to avoid some types of complications caused by externally placed catheters this system serves another important goal in palliative cancer treatment: an improved quality of life, as a good ambulatory implementation is secured.

Antineoplastic Agents↗

Pirarubicin (4'-o-tetrahydropyranil-adriamycin) for treatment of advanced breast cancer. A Clinical Phase II study.

In a phase II study, 77 patients with metastatic breast cancer were treated with pirarubicin, 70 mg/m2 iv every 3 weeks. Most of them had received prior hormonal (n = 39) and/or chemotherapeutic drug treatment for advanced disease, including anthracycline-containing regimens in 17. After a median of 5.5 treatment cycles (range 1-14), objective tumor response was seen in 22/71 (31%) evaluable patients (4CR, 18 PR). Stable disease occurred in 34 (48%) patients, whereas the tumor progressed in 15 (21%). Significant hematologic toxicity (WHO grade III-IV) requiring interval and/or dose adjustments was observed in 41 (58%) patients. Other treatment-related side effects were generally mild, and included alopecia in 52 (73%), nausea and/or emesis in 50 (70%), and stomatitis and diarrhea in 3 patients each. There was no treatment-related death, nor was there any evidence of cardiac toxicity thus far. In summary, the early results of this trial suggest that pirarubicin is an active and rather well tolerated drug in pretreated patients with advanced breast cancer.

Adult↗

Hepatic artery infusion chemotherapy.

Hepatic artery chemotherapy was given to 36 patients, using totally implantable devices consisting of a port and external pump. Twenty-seven patients had inoperable liver metastases of colorectal origin. The infusion system was inserted by laparotomy into the hepatic artery via the gastroduodenal artery. There was no operative mortality. Thirteen infusion systems could not be used for chemotherapy due to dislodgement, early death and lack of follow-up. FUdR was infused every two weeks. There were minor local complications like thrombosis of the system and dislodgement of the port. Toxic effects could be managed by reducing the dose. Response to chemotherapy was evaluated by survival, clinical condition, CEA, ultrasound and CT six months after onset of arterial chemotherapy. Ten/twenty-three patients (43%) responded to therapy, eight of them died on the average 19 months after initial chemotherapy. Six patients were non-responders, seven had stable disease. Five/ten patients developed extrahepatic metastases. Mean survival time was 13.1 months, mean interval until relapse 10.6 months.

Adult↗

Bacillus Calmette-Guérin treatment and vesicorenal reflux.

14 patients with radiologically documented vesicorenal reflux (5 bilateral, 7 unilateral, 2 unilateral double-J stents) received intravesical immunotherapy with bacillus Calmette-Guérin (BCG) after treatment of their superficial urothelial tumors. 1 patient with a double-J stent suffered a highly febrile attack following obstruction of the indwelling ureteral catheter. The other patients tolerated 1 or 2 (6 of 14 patients) courses of BCG without an increase in side effects. Topical intravesical therapy with BCG in patients with vesicorenal reflux seems to be indicated in view of the multicentricity of urothelial carcinoma and can be performed without an increased risk of complications.

Administration, Intravesical↗

[Diverticular calculi of the kidney calices--extracorporeal shockwave lithotripsy, percutaneous extraction or open surgery].

The incidence of caliceal diverticula, mostly found on routine excretory urography, is very low. The indications for treatment include chronic or recurrent pyelonephritis, pain, gross hematuria and renal damage. There is controversy as to which treatment is best: extracorporeal shock-wave lithotripsy (ESWL), percutaneous techniques, or traditional open surgery. Since 1984, 27 patients with 28 caliceal diverticula calculi have been treated. Ten patients underwent ESWL, 13 patients percutaneous treatment, and 4 patients open surgery. The success rates as far as a stone-free status is concerned were: 1 patient (ESWL), 10 (percutaneous), and 4 (open surgery). There were no complications due to ESWL or open surgical treatment. Direct traumata such as severe bleeding in two and hydrothorax in one patient occurred during the training phase of the percutaneous techniques. Due to the low complication rate, non-invasive ESWL treatment should be tried first. The indications for percutaneous removal of calculi in caliceal diverticula depend on two aspects: it should be possible to puncture the caliceal diverticula via by a short parenchymal route coaxial to the axis of the calix and, if the intercostal approach is used, a pleural lesion must be excluded. If these requirements cannot be fulfilled, open surgical treatment should be performed, especially if the diverticula are located in the upper and anterior part of the kidney.

Adolescent↗

[Tumor diagnosis by immunoscintigraphy with anti-CEA antibodies (Tc-99m MAK BW 431/26)].

We evaluated the clinical application of the monoclonal antibody MAb, BW 431/26, which is easy to label with Tc-99m for tumor localization. This is an anti-CEA antibody and a murine immunoglobulin (Ig G1, Isotype). We investigated patients with colorectal carcinoma (n = 14), with colorectal carcinoma recurrences (n = 24), breast carcinoma (n = 2), stomach carcinoma (n = 1), carcinoma of the urinary bladder (n = 3), lung carcinoma (n = 2) and patients with an elevated CEA level. In primary colorectal tumors (n = 14) all carcinomas were correctly localized by IS and ECT technique. In these patients the diagnosis was already known. The planar pictures showed a false negative result in 3 patients. In patients with colorectal recurrences the investigations were performed twice in 2 patients and three times in 1 patient. In these 31 ECT investigations we found 17 true positive results, 12 true negative results, 1 false positive result and 1 false negative result. The lesions were already visualized within 4 to 6 hours, but 24-hour pictures are desirable. SPECT pictures are absolutely necessary because sensitivity is considerably improved thereby. Elevated CEA levels increase the probability of a positive IS low CEA levels do not exclude positive tumor visualization. HAMA was found in only 1 patient, but follow-up investigations are indicated.

Adult↗

[Treatment of distal urethral cancer by laser coagulation].

Primary carcinoma of the urethra is a rare lesion, and there are no standard therapeutical modalities suggested in the literature. We report the case of a 65-year-old woman with transitional cell carcinoma of the distal urethra and metastasis to the inguinal lymph nodes (T2 N1 MO G2). Locally, the lesion was treated by Nd:YAG laser coagulation in four sessions. Ileoinguinal and pelvic lymph-node dissection was performed as a diagnostic and therapeutic procedure. Twenty-eight months after the initial treatment, no evidence of tumor recurrence has been found, although extensive biopsy specimens have been taken. Clinical staging showed no evidence of metastases.

Biopsy↗

[BCG in reflux].

Nine patients with radiologically proven vesicorenal reflux (3 bilateral, 4 unilateral, 2 with unilateral double-J stents) received intravesical bacillus Calmette-Guérin (BCG) as prophylactic treatment for recurrent superficial bladder carcinoma. One patient with a double-J stent suffered an attack of high fever, probably following obstruction of the stent. All other patients tolerated one cycle or two cycles (5 of 9 patients) of 6 weekly instillations without significant complications. There was no increased toxicity compared with a control group of 39 patients without reflux who were receiving BCG. Topical intravesical immunotherapy with BCG in patients with vesicorenal reflux can be given without a rise in the complication rate; indeed, in view of the multifocal appearance of urothelial carcinoma in this subgroup, this type of therapy even appears to be desirable.

Administration, Intravesical↗

Escalating dose regimen of intraperitoneal mitoxantrone: phase I study--clinical and pharmacokinetic evaluation.

Mitoxantrone, a recent anthracenedione derivative, is a potentially useful drug for direct intraperitoneal (i.p.) application because of its high tissue binding and therapeutic index. We have carried out studies to establish maximum tolerated doses as well as pharmacokinetic studies with i.p. mitoxantrone in 21 patients (5 male, 16 female) with gastrointestinal (9), ovarian (6), unknown (2) and other (4) primary cancers and peritoneal carcinomatosis. Increasing doses (10-40 mg/m2) were given i.p. every 4 weeks. Five partial remissions (2-8+ months) and 7 stable disease courses (2-6+ months) were achieved. A reduction or disappearance of ascites was seen in an additional 3 patients. Severe toxicity (leucopenia) was observed in 4 patients only after 35 and 40 mg/m2 i.p. Pharmacokinetic analysis using high performance liquid chromatography yielded the following data: The mean ratio of area under curve peritoneal fluid to plasma was 1109. The peritoneal clearance rate was 680 ml/min and the mean disappearance half life was 13.1 h. Mean urinary excretion within 24 h was 0.42% of the i.p. dose. These data indicate that mitoxantrone is sequestered in the intraperitoneal tissue compartment and only slowly released. Based on the outcome of this phase I study we recommend phase II studies at a dose of 30 mg/m2 i.p., repeated every 3-4 weeks.

Adult↗

Phase-I study of intraperitoneal mitoxantrone--clinical and pharmacokinetic evaluation.

Mitoxantrone, a recent anthracenedione derivative is a potentially useful drug for direct intraperitoneal (i.p.) application because of its high tissue-binding and therapeutic index. We have carried out studies to establish maximum tolerated doses as well as pharmacokinetic studies with i.p. mitoxantrone in 21 patients (5 male, 16 female) with gastrointestinal (9), ovarian (6), unknown (2) and other (4) primary cancers and peritoneal carcinomatosis. Increasing doses (10-40 mg/m2) were given i.p. every 4 weeks. Five partial remissions (2-8+ months) and 7 stable disease courses (2-6+ months) were achieved. A reduction or disappearance of ascites was seen in an additional 3 patients. Severe toxicity (leukopenia) was observed in 4 patients only after 35 mg/m2 and 40 mg/m2 i.p. Pharmacokinetic analysis using high-performance liquid chromatography yielded the following data: The mean ratio of area under curve peritoneal fluid to serum was 1,108. The peritoneal clearance ranged from 2 ml/min to 9,617 ml/min and the disappearance half-life from 0.6-28.9 h. Mean urinary excretion within 24 h was 0.42% of the i.p. dose. These data indicate that mitoxantrone is sequestered in the intraperitoneal tissue compartment and only slowly released. Based on the outcome of this phase-I study we recommend phase-II studies at a dose of 30 mg/m2 i.p., repeated every 3-4 weeks.

Drug Evaluation↗

Endoscopic intubated ureterotomy.

On the basis of our experience with 9 cases, endoscopic ureterotomy for ureteral stenoses represents an alternative to open reconstructive surgery. In cases of acquired ureteral stenoses, the transurethroureteral access appears to be the method of choice. In contrast to open surgery, particularly after previous operations, surgical trauma is minimal. A primary attempt at ureteroscopic ureterotomy is warranted, since it does not appear to pose any problems for open surgery should this prove necessary later.

Adult↗

[Intraoperative, endoscopic lithotripsy of pancreatic duct calculi. A contribution to the surgical treatment of chronic calcifying pancreatitis].

The problem of chronical calcifying pancreatitis is demonstrated in two female patients. Resection of the pancreas is necessary, if prepapillar concrements cannot be extracted. By two new techniques, ultrasound-lithotripsy and laser-induced shock-wave-lithotripsy, it is possible to destroy concrements and to remove them. These new techniques are now used primarily in surgery.

Adult↗

CHOP-firstline treatment in NHL with unfavorable prognosis--evaluation of therapeutic response and factors influencing prognosis.

58 NHL-patients (9 large cell centrocytic, 18 centroblastic, 16 immunoblastic, 15 lymphoblastic lymphomas) were treated immediately after diagnosis with CHOP-chemotherapy regardless of the extent of disease. Because of the advanced age of the majority of patients (median age 61 years, range 22-85 years) a reduced dose in the first two cycles was administered. Statistically significant prognostic variables influencing survival were the following: histologic subtypes according to the Kiel-classification (p less than 0,05), B-symptoms (p less than 0,001), blood sedimentation rate (p less than 0,02) and LDH (p less than 0,0005). With regard to prognosis there was no difference between patients over 60 years of age and younger ones (p less than 0,4). Patients achieving complete remission survived significantly longer (p less than 0,0001). Ann Arbor stages were of limited value, since patients with CS II disease and accumulation of risk factors (B-symptoms, abdominal disease, bulky tumor masses) showed a poorer outcome than patients with CS III who did not have these risk factors. A risk factor score summarizing features influencing prognosis is described and might be a useful tool in stratifying the heterogeneous group of NHL with unfavorable prognosis.

Adult↗