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J Funovics

Publications and source records attributed to J Funovics.

At least 19 recordsLinked to original sources
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↗
PubMed1999

Phase II trial of gemcitabine, epirubicin and granulocyte colony-stimulating factor in patients with advanced pancreatic adenocarcinoma.

Although the novel cytidin analogue gemcitabine has shown superior anti-tumour activity than 5-fluorouracil in advanced pancreatic cancer, further improvements of therapeutic results are warranted. This goal might be achieved by combining gemcitabine with other active drugs. This trial evaluated the efficacy and tolerance of such a combination regimen with epirubicin and granulocyte colony-stimulating factor (G-CSF) in patients with metastatic disease. Seventy patients with metastatic pancreatic adenocarcinoma were enrolled in this multicentre trial. Patients received 4-weekly courses of a combination regimen consisting of epirubicin 60 mg m(-2) given as intravenous bolus injection on day 1, gemcitabine 1000 mg m(-2) infused over 30 min on days 1, 8 and 15, and G-CSF administered at 5 microg kg(-1) day(-1) subcutaneously from days 2-6 during each cycle. The efficacy of treatment was assessed by conventional measures, i.e. objective response, progression-free and overall survival, as well as by analysis of clinical benefit response (defined as > or = 50% reduction in pain intensity, > or = 50% reduction in daily analgesic consumption, and/or > or = 20-point improvement in Karnofsky performance status that was sustained for > or = 4 consecutive weeks). Of 66 patients evaluable for objective response, one achieved complete and 13 partial remissions, for an overall response rate of 21% (95% confidence interval (CI), 12-33%); 27 additional patients (41%) had stable and 25 (38%) increasing disease. The median time to progression was 3.8 months. Median survival was 7.8 months, and the probability of surviving beyond 12 months was 21.2%. Out of 60 patients with tumour-related symptoms, who were considered evaluable for clinical benefit response, 26 (43%) experienced significant palliation. The median time to achieve a clinical benefit response was 7 weeks, and its median duration was 22 weeks. Chemotherapy was well-tolerated with leukopenia/granulocytopenia representing the most common and dose-limiting side-effect. Gastrointestinal and other subjective toxicities were infrequent and generally rated minor. We conclude that the combination of gemcitabine, epirubicin and G-CSF seems to be an effective palliative treatment with only moderate toxic effects in patients with metastatic pancreatic adenocarcinoma. Our results in terms of objective and clinical benefit response, as well as survival seem to suggest an advantage over gemcitabine-monotherapy, though this remains to be confirmed in a randomized trial.

Adenocarcinoma↗
PubMed1992

A phase II trial of 5-fluorouracil, leucovorin, and recombinant alpha-2b-interferon in advanced adenocarcinoma of the pancreas.

BACKGROUND: Preclinical and clinical data suggest that both leucovorin (LV) and interferon (IFN) can augment the cytotoxic effects of 5-fluorouracil (5-FU). Based on the rationale of biochemical double modulation, the current Phase II study was undertaken. METHODS: Thirty-two previously untreated patients with advanced adenocarcinoma of the pancreas were treated with subcutaneous recombinant alpha-2b-IFN at a dose of 10 million units on 3 consecutive days; LV (200 mg) plus 5-FU (20 mg/kg) were administered as intravenous bolus doses on day 3. Treatment courses were repeated as tolerated in 2-to-3-week intervals, depending on the patient's complete blood count. RESULTS: Of 32 evaluable patients, 4 (12.5%) had a partial response (95% confidence limit, 4-30%) of 4, +6, 7.5, and 9 months' duration, and 13 (40.5%) had stable disease. The median duration of survival for all patients from the start of therapy was 5.5 months. The most common toxicities observed were IFN-related fever during the first course (69%), mild leukopenia (53%), and gastrointestinal symptoms (28%). CONCLUSIONS: Although the combination of 5-FU, LV, and recombinant alpha-2b-IFN in patients with advanced pancreatic adenocarcinoma has some activity and generally was well tolerated, the observed response rate and median survival were not superior to 5-FU monotherapy.

Adenocarcinoma↗
PubMed1990

Sequential high-dose methotrexate, 5-fluorouracil, and doxorubicin for treatment of advanced pancreatic cancer.

A phase II trial of sequential high-dose methotrexate, 1500 mg/m2, and 5-fluorouracil, 1500 mg/m2 intravenously on day 1, plus doxorubicin, 30 mg/m2 i.v. on day 14, has been undertaken in patients with locally advanced or metastatic adenocarcinoma of the pancreas. Of 25 evaluable patients there were 1 complete response and 3 partial responses for an overall response rate of 16% (95% confidence interval 5%-36%). The median survival of all patients was 6.7 months (range 1-17 months). There was one treatment-related death due to pancytopenia and sepsis. In all other patients therapy was generally well-tolerated. We conclude that this combination protocol has only modest activity in the treatment of advanced pancreatic cancer.

Adult↗
PubMed1990

[Blunt pancreatic trauma].

21 blunt pancreatic injuries were reviewed over a 22 year period. Only four of them were admitted directly to the Trauma Center, while the others were referred because of pancreatic complications. Twelve of the patients developed significant pancreatic complications. Sepsis causing death in two cases were attributed directly to the pancreatic injury. The subsequent report examines the question of distal resection with drainage, which was performed eight times and the clinical outcome after an average posttraumatic period of 11.6 years.

Acute Disease↗
PubMed1990

Patency rate of implantable devices during long-term intraarterial chemotherapy.

Intraarterial implantable drug delivery systems have been considered as an alternative method for treating patients with unresectable liver malignancies. However, catheter problems with external implanted devices have resulted in limited application of chemotherapy. The introduction of subcutaneous devices offers an opportunity for long-term locoregional chemotherapy. Twelve external intraarterial catheters were implanted into 12 patients and 52 subcutaneously placed devices into 51 patients, all with various hepatic malignancies. Retrospective analyses comparing those two intraarterial systems were conducted taking into account the function and complication rate (hepatic artery thrombosis, infection, leaking, hemorrhage, and dislocation). The follow-up time for the external system was two to eight months (median five weeks), the thrombosis rate 33.3%, and the infection rate 25%. One instance of severe bleeding from the hepatic artery occurred during chemotherapy. One catheter dislocated. For the subcutaneously implanted intraarterial devices the follow-up time was five to forty-one months (median sixteen months), the thrombotic complication rate 17.3%, and the infection rate 7.6% (all patients with simultaneous bowel surgery). Catheter dislocation one year later required reimplantation; in 1 patient therapy had to be discontinued because of a catheter leak. The overall function rate was 71.3% with a median follow-up time of eight months. Anticoagulation therapy for subcutaneously implanted devices starting from the beginning of intraarterial chemotherapy is recommended to achieve long-term patency. No implantation should be preformed simultaneously with bowel surgery. The subcutaneously placed intraarterial devices had a higher function rate and were available for a longer period as compared with external implanted catheters.

Equipment Failure↗
PubMed1988

Impaired cell-mediated immunity in the first week after burn injury: investigation of spontaneous blastogenic transformation, PHA, IL-2 response and plasma suppressive activity.

This study investigated alterations of cell-mediated immunity induced by trauma, operative treatment and infections in a group of 19 burned patients with a mean burn size of 42 +/- 22 per cent of the body surface area. We tested peripheral mononuclear blood cells (PMBC) for spontaneous blastogenic transformation (SBT), phytohaemagglutinin (PHA) and interleukin-2 (IL-2) responsiveness. Plasma samples were also assayed for inhibition of mitogen stimulation of control PMBCs. Mean values were calculated for the acute postburn period (days 0-3) and the following 4 days, before the development of septic complications. SBT was significantly increased in all patients during the second period of investigation (days 4-7) in comparison to normal controls and during the acute phase. The response to mitogen stimulation (PHA) was significantly suppressed during days 0-7 and the plasma samples showed high suppressive activities following PHA stimulation of control lymphocytes during the course of the study. No significant differences in rates of SBT, PHA responsiveness and plasma suppressive activity were found between those patients who developed bacteraemia and those with negative blood cultures. The latter group showed higher reactivity to added IL-2 in comparison to normal controls. Surgical treatment immediately after trauma (fasciotomy; day 0 or 1) resulted in further increased immunosuppression (PHA and IL-2 response), whereas after necrectomy (days 4-7) the immunological parameters showed no significant differences. It can be concluded that neither rates of SBT nor response to PHA can be used to identify patients at high risk for infection during the first week postburn.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Alanylglutamine reduces muscle loss of alanine and glutamine in post-operative anaesthetized dogs.

1. The present study examined the effect of an infusion of the dipeptide alanylglutamine or of the corresponding amino acids alanine and glutamine in equimolar amounts (10 mumol min-1 kg-1) on the canine hindlimb exchange of alanine and glutamine in the post-operative anaesthetized dog. In contrast to glutamine, the dipeptide alanylglutamine is stable in aqueous solution and therefore would be a suitable substrate for parenteral nutrition. 2. The infusion of alanylglutamine increased (a) the arterial concentration of alanylglutamine to a plateau level (120 +/- 9.5 mumol/l, mean +/- SEM) 20 min after start of the infusion, (b) the mean arterial alanine concentration from 761 +/- 42 to a plateau of 1500-1700 mumol/l (P greater than 0.01) and (c) the arterial glutamine concentration from 407 +/- 51 to a plateau of 1050-1500 mumol/l (P greater than 0.01). Alanine and glutamine levels were slightly higher (14% and 26%, respectively, NS) in the group receiving the equimolar amount of alanine and glutamine. 3. Infusion of alanylglutamine for 1 h abolished the net efflux of glutamine (from -0.80 +/- 0.1 to -0.03 +/- 0.2 mumol min-1 kg-1; P greater than 0.05) and invoked a net influx of alanine (from -0.50 +/- 0.19 to +0.27 +/- 0.14 mumol min-1 kg-1; P greater than 0.01). These changes were similar to those achieved when the two amino acids were infused. 4. This study demonstrates that during short-term administration of alanylglutamine or of the corresponding amino acids the nitrogen release from the hindlimb of the anaesthetized post-operative dog via alanine and glutamine is reduced.

Alanine↗
PubMed1988

[Chemotherapy of advanced pancreatic cancer with 5-fluorouracil, doxorubicin and high-dose methotrexate].

The aim of the present phase II clinical trial was to investigate the therapeutic efficacy and tolerance of a combination chemotherapeutic protocol consisting of 4-weekly intervals of 5-fluorouracil, doxorubicin and high-dose methotrexate (FAMeth-regimen) in patients with advanced measurable pancreatic cancer. After a median treatment duration of 4 (2-12) months, one complete and one partial response were achieved in the 13 evaluable patients. Two additional patients had evidence of objective tumour regression, although response was less than 50% of pretreatment tumor measurements. Stable disease was noted in 3 patients, and the tumour progressed in 6. The median survival of all evaluable patients from start of therapy is 7 (2-17) months. Side-effects associated with FAMeth-chemotherapy were generally mild and reversible and primarily included gastrointestinal symptoms (38%) and leukopenia (62%). There was 1 treatment related death due to pancytopenia and sepsis. Our preliminary data suggest some antitumour activity of the regimen against pancreatic cancer, although final assessment of therapeutic results must await accrural of additional patients.

Adult↗
PubMed1988

[Accomplishments of tumor surgery in tumors of the lymphatic system].

Malignant lymphomas behave like localised tumors and should be removed by radical operation. Stage, histology, type of surgery and postoperative therapy significantly influence prognosis. Curative resections should be carried out in stage I/1 and I/2, palliative resections in all other stages. Postoperative radiotherapy and/or chemotherapy is currently obligatory in all stages except I/1 and I/2.

Combined Modality Therapy↗
PubMed1987

[Toxicity results of an adjuvant study with intraperitoneal chemotherapy in patients with stomach cancer. Current status and future prospects of intraperitoneal therapy].

The peritoneum is a frequent location of recurrent disease after surgical treatment of carcinoma of the stomach, colon, rectum or ovary. Usually this type of recurrence does not respond very well to systemic chemotherapy. The rational of intraperitoneal (ip) perfusion with cytotoxic drugs is based on a 2- to 3-log-fold increase in ip level over plasma concentration for certain chemotherapeutic agents. Hence, malignant cells in the peritoneal cavity can be exposed to very high concentrations of cytotoxic agents without serious systemic side effects. Remission rates of peritoneal carcinoma after ip perfusion of a range of chemotherapeutic substances varied from between 15 to 50%. Minimal information is available about adjuvant ip perfusion after operation for cure. Toxicity data are presented from our adjuvant trial using ip perfusion after operation for gastric carcinoma for cure with cisplatin in a randomized fashion. Altogether 59 perfusions were performed, with minimal systemic toxicity, no occurrence of peritonitis and only 1 portal infection. Immunological data show that 1 day after ip perfusion the concentration of natural killer cells is increased in 60% of all perfusions, but decreased only in 28%. We conclude that ip perfusion with cisplatin is a safe procedure with limited toxicity. The efficacy of this technique in peritoneal carcinosis is not yet proven in randomized trials. The observation period of our trial in the adjuvant stage after operation for gastric carcinoma is too short as get to assess the usefulness of the procedure.

Antineoplastic Agents↗
PubMed1987

Free amino acid levels in muscle and liver of a patient with glucagonoma syndrome.

This study set out to measure the amino acid concentrations in the femoral artery, femoral vein, hepatic vein, muscular and hepatic tissue, and urine of a patient with the glucagonoma syndrome. The total plasma amino acid concentration was severely reduced on admission (737 mumol/L, 26% of normal), with only a slight increase during intravenous administration of 200 g of amino acids per day. The total intracellular amino acid levels in the muscle were 86%, and those of the liver were 47% of the normal range. Only 0.62% of the amino acids administered were found in the urine. Arteriovenous amino acid concentration differences across the muscle and splanchnic tissue indicated the release of amino acids (mainly glutamine, glycine, and alanine) from the muscle and the absorption of amino acids by the splanchnic bed. This study shows that the infusion of a high amount of amino acids cannot increase the subnormal plasma AA levels of patients with the glucagonoma syndrome. The low total plasma AA levels are paralleled by decreased intracellular free amino acid levels in the muscle and liver.

Adenoma, Islet Cell↗