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Biomedical subjects

Z Grahovac

Publications and source records attributed to Z Grahovac.

13 recordsLinked to original sources
PubMed1993

Feasibility study of intraarterial vs intravenous cisplatin, BCNU, and teniposide combined with systemic cisplatin, teniposide, cytosine arabinoside, glycerol and mannitol in the treatment of primary and metastatic brain tumors.

Sixteen patients with intracerebral tumors received intraarterial cisplatin, teniposide, and BCNU combined with intravenous cisplatin, teniposide, and cytosine arabinoside. Oral glycerol and intravenous mannitol were given along with the intravenous chemotherapy in an attempt to increase drug delivery to tumor by augmenting tumor blood flow. Thirteen additional patients were treated with the same regimen, but received all the chemotherapy intravenously. Of the 16 patients receiving intraarterial chemotherapy (median survival, 14 weeks), none responded, 5 (31%) were stable for > 8 weeks, 8 (50%) failed, and 3 (19%) were unevaluable due to early death. Of the 13 patients receiving all their treatment intravenously (median survival, 13 weeks), 3 (23%) responded, 1 (8%) was stable, 7 (54%) failed, and 2 (15%) were unevaluable due to early death. In the patients receiving intraarterial chemotherapy, toxicity included ipsilateral retinal toxicity (2 patients), ocular pain or headache (10), periorbital swelling and flushing (6), increased brain edema with focal neurological deficits and drowsiness (5), and catheter-related carotid artery thrombosis followed by fatal herniation (1). Myelosuppression was worse in patients who received all their treatment intravenously than in those receiving intraarterial chemotherapy (p < 0.05). Neutropenic sepsis developed in 4 patients on the intraarterial arm (1 fatal) and in 5 patients on the intravenous arm (2 fatal). Other toxic effects were similar whether or not patients received intraarterial treatment or only intravenous treatment. Overall, toxicity of this regimen was excessive, and response rates were lower than would have been expected with single agent therapy.

Adult↗
PubMed1992

Phase I study of intracarotid administration of carboplatin.

Fifteen patients were treated in a Phase I study of intracarotid carboplatin (200-400 mg/m2) in 5% dextrose and water infused over 15 to 30 minutes through a transfemoral catheter with a 0.2-micron inline filter. This study was done because intravenous carboplatin has less neurotoxicity than cisplatin and is active against brain tumors. Eleven men and four women ranging in age from 37 to 72 years (median, 59 years) were treated. The Eastern Cooperative Oncology Group performance status was 1 in 3, 2 in 4, and 3-4 in 8 patients. Eight patients had one to three previous chemotherapy regimens; previous radiotherapy had failed in 13 patients. The response of patients in the Phase I study follows: glioblastoma, 6 failed; not evaluated because of early death from pulmonary embolus, 1; recurrent Grade II and III glioma, 1 stable (minor response with neurologic improvement) and 2 failed; malignant oligodendroglioma, 1 failed; brain metastases from nonsmall cell lung cancer, 1 partial remission, 1 stable (minor response), and 1 failed; brain metastases from unknown primary, 1 stable (minor response with neurological improvement). Median survival was 9 weeks. Nausea was mild to moderate. One patient had granulocytopenia, and 2 had thrombocytopenia (mild). At 200 mg/m2 (2 patients), 1 had a focal seizure. At 300 mg/m2 (9 patients), 2 with abnormally small arteries had severe pain early in the treatment and posttreatment ipsilateral conjunctival edema, decreased vision, and cerebral edema (with partially reversible increased hemiparesis); 1 other had mild decrease in ipsilateral vision and 1 had transient aphasia on removal of the catheter (possibly the result of a vascular spasm).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Phase I study of intracarotid PCNU.

A phase I study of the intracarotid administration of PCNU was conducted in patients with intracerebral tumors recurring after cranial radiation. Seventeen patients were treated including 16 with recurrent gliomas or glioblastomas and 1 with recurrent brain metastases from adenocarcinoma of the lung. An additional patient received a vertebral artery infusion of PCNU for a recurrent glioblastoma. Seven of 17 patients receiving intracarotid PCNU responded for a response rate of 41%. If only evaluable patients with gliomas are considered, the response rate was 44%. Tumor grade at time of initial diagnosis, exposure to prior chemotherapy, and dose of PCNU did not appear to have a major impact on response rate. Zubrod performance status 3 patients had a lower response rate (25%) than did patients with performance status 1 or 2 (response rate 63%). Thrombocytopenia and reversible central nervous system toxicity were dose limiting at a PCNU dose of 110 mg/m2. Two patients had possible permanent central nervous system toxicity. Three patients had permanent ipsilateral visual impairment, including one at the lowest dose used into the carotid artery (60 mg/m2). Orbital pain appeared to be substantially less than that seen with intracarotid BCNU but headaches may have been somewhat more common. The single patient receiving a vertebral artery infusion developed marked headaches and restlessness after receiving 25 mg/m2 of a planned 75 mg/m2 treatment into the vertebral artery and the treatment had to be discontinued. Symptoms were rapidly reversible upon stopping the medication. Our overall impression is that intracarotid PCNU causes less ocular pain but more transient central nervous system toxicity than does intracarotid BCNU.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Intraarterial mitomycin-C for recurrent brain metastases.

Fifteen consenting patients with brain metastases recurrent after cranial irradiation were treated with intraarterial mitomycin-C, 15 mg/m2, administered in a total final volume of 100 ml 0.45% saline over 20 min through a transfemoral catheter with a 0.2-mu in-line filter. There were 2 early deaths (one probably drug-related). Of the 13 evaluable patients, 6 (46%) responded, with both computed tomography (CT) scan and neurological improvement. Median response duration was 25 weeks, and median survival of all 15 patients was 17 weeks. Neurological, ocular, and local skin toxicity were dose-limiting. The degree of toxicity was comparable to that we have noted with other intracarotid regimens, and it appears to be less toxic when infused into the vertebral artery than are most other drugs (although experience is still limited and caution still needs to be exercised). We do not recommend that this replace or be added to cranial irradiation as front-line treatment of brain metastases, but we feel that it is an effective and reasonably well-tolerated regimen for treatment of brain metastases that have recurred after cranial irradiation. We are currently initiating studies of intraarterial mitomycin-C combined with intraarterial cisplatin and teniposide (VM-26) as treatment for recurrent brain metastases.

Adolescent↗
PubMed1987

Combined intraarterial and systemic chemotherapy for intracerebral tumors.

Twenty-six patients with intracerebral tumors (predominantly gliomas) were treated with intraarterial BCNU, VM-26, and cisplatin combined with the systemic administration of VM-26, methotrexate, vincristine, bleomycin, and procarbazine. Oral glycerol was given before i.v. VM-26. Twelve patients responded (46% of all patients and 63% of the fully evaluable patients). The response rate for gliomas was 50% if all patients were considered and 71% if only fully evaluable patients were considered. The response rate did not seem to be affected by glioma grade, prior chemotherapy, or pretreatment performance status. Median time to tumor progression for responders was 19 weeks. Median survival from initiation of treatment was 21 weeks for evaluable patients and 17 weeks for all patients. Median survival from initial diagnosis was 55 weeks. Myelosuppression was dose-limiting for the systemic chemotherapy. Reversible neurological toxicity was common, but tolerable. One patient developed ipsilateral blindness, and two patients developed prolonged neurological toxicity. Pulmonary toxicity was also seen. Vertebral artery infusions proved feasible, although difficult and more toxic than carotid infusions. Overall, this regimen was not more active than the intraarterial combination of BCNU, VM-26, and cisplatin without the systemic chemotherapy. Further studies of more intensive intracarotid therapy combined with different systemic drugs are being initiated.

Adolescent↗
PubMed1984

Cisplatin plus cytosine arabinoside in adults with malignant gliomas.

A combination of cisplatin and cytosine arabinoside was used to treat 21 patients with glioblastomas and 5 patients with recurrent grade II gliomas. Cisplatin 60-100 mg/m2 was given I.V. in 250 ml 0.45% saline and preceded by 500 ml dextrose 5% in 0.45% saline. Mannitol 50 g was given I.V. concurrently with the cisplatin. Cytosine arabinoside 500-1000 mg/m2 was given by rapid I.V. infusion immediately after the cisplatin. Of 25 evaluable patients, 10 (40%) experienced objective tumor shrinkage on CT scan, and 6 (24%) stabilized. There were 2 complete remissions. Patients who had had no prior treatment had a higher response rate (58%) than those previously treated (23%). Myelosuppression occurred in some patients 2-3 weeks after treatment. Gastrointestinal toxicity (vomiting and diarrhea) was dose-limiting. Two patients had possible neurological toxicity. Recommended doses for further studies are cisplatin 90 mg/m2 and cytosine arabinoside 900 mg/m2.

Adult↗
PubMed1984

Treatment of malignant gliomas in adults with BCNU plus metronidazole.

Twenty-six adult patients with astrocytomas were treated with BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea) 180-240 mg/m2 I.V. every 6-9 weeks, with metronidazole 1.5 g/m2 p.o. 12 h and 1 h before BCNU and again 6 h and 24 h after BCNU. Of twenty-two evaluable patients, 9 (41%) responded with evidence of reduced tumor size on CT scan, 3 (14%) stabilized and 10 (45%) failed. Patients with no prior chemotherapy or radiotherapy, good performance status, low grade tumors, and age less than or equal to 50 years had the highest response rates, although differences were not statistically significant. Median survival and duration of response have not been reached with a median follow-up time of ten months. Hematological toxicity was dose-limiting and was probably not augmented by the metronidazole. There was one death from infection that was possibly drug-related. Gastrointestinal toxicity was substantial, and was probably increased by the metronidazole. While the combination of BCNU and metronidazole were tolerable, the response rate seen was no higher than that noted for BCNU alone, and further studies using this dose-schedule are not recommended in astrocytomas.

Adult↗
PubMed1984

Intracarotid chemotherapy with a combination of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), cis-diaminedichloroplatinum (cisplatin), and 4'-O-demethyl-1-O-(4,6-O-2-thenylidene-beta-D-glucopyranosyl) epipodophyllotoxin (VM-26) in the treatment of primary and metastatic brain tumors.

Thirty-seven patients with intracranial primary or metastatic tumors were treated with an intraarterial combination of BCNU, cisplatin, and VM-26 to determine the efficacy, toxicity, and maximal tolerated doses for the combination. A transfemoral fluoroscopic approach was used to catheterize temporarily the internal carotid or vertebral artery. Thirteen of 19 (68%) evaluable primary brain tumors and 9 of 16 (56%) evaluable brain metastases responded. The response rate was lower in patients previously treated with both cranial irradiation and i.v. chemotherapy than in patients less heavily pretreated (54% vs. 82%), although even patients previously treated i.v. with all three of the study drugs responded. All five patients with both extracranial and intracranial evaluable tumor deposits experienced a greater response of their intracranial than of their extracranial tumor. Ipsilateral retinal and neurological toxicity were dose-limiting, with major toxicity (permanent decreased vision or hemiparesis) occurring in five of nine (56%) patients receiving doses of BCNU greater than or equal to 100 mg/m2 plus cisplatin, 60 mg/m2 plus cisplatin, 60 mg/m2, plus VM-26, 175 mg/m2. Only 9% of the patients treated with a lower VM-26 dose developed permanent severe toxicity, and the doses that we now recommend are: BCNU, 100 mg/m2; cisplatin, 60 mg/m2; and VM-26, 150 mg/m2. The response rate was also dose-related (100% at the highest doses tested vs. 57% at the lower doses).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1983

[Peak blood levels of mepivacaine following intravenous regional anesthesia using various concentrations].

In a previous study we assumed, that with I.V.R.A. the peak blood levels after opening the tourniquet would be less when lowering the concentration and simultaneously increasing the volume of the anesthetic solution. For supporting this hypothesis, on 17 patients each the peak blood levels of mepivacaine after I.V.R.A. were determined. For this a 0.25% (gr. A) and 0.50% (gr. B) concentration of solution was given. The same absolute amount (3.75 mg/ml b.w.) of the anesthetic was used and the measured values are compared. The results show a median for the 0.25% solutions of XA = 4,046 ng/ml and for the 0.50% ones of XB = 6,894 ng/ml. The values differ for p less than 0.05 with the onesided mediantest. Our initial assumption is confirmed which consequently contributes to greater safety.

Adolescent↗
PubMed1982

[Prospective comparative study of postspinal headaches in young patients (less than 51 years)].

1.009 patients (less than 51 years) were investigated for the frequency of postspinal headaches developing when using different types of needles (22 G and 25 G with Quincke-cut and 22 G Whitacre-needle). It was shown, as expected, that puncture with the smaller needles caused with 6% only about half as many headaches as did taps with the two bigger types of needles, which did not demonstrate any statistical difference between each other. After classifying the complaints as doubtful and definite postspinal headaches the rates of real headaches of the total series was about 5%. The highest frequency of complaints was reported by female patients in the 5th decade. An increase with lesser age was not noticed. Technical difficulties associated with spinal puncture were of almost no importance in influencing the rate of headaches. Definite bloody taps were associated with significantly higher complaint rates. The drugs used (mepivacaine and bupivacaine) did not appear to have any influence. An advantage of the more expensive Whitacre-needle is not seen except in patients with disturbances of coagulation factors.

Adolescent↗
PubMed1981

[Clinical aspects of intravenous regional anaesthesia (I.V.R.A.) (author's transl)].

3 groups of patients undergoing upper extremity surgery were anaesthetized with I.V.R.A. They were prospectively investigated to determine their absolute need of drug and the failure rate. As anaesthetics 0.50%, 0.33% and 0.25% mepivacaine solutions were used. It was found that the reduction in concentration with a combined increase in volume leads to a higher success rate and a simultaneous reduction of the absolute amount of drug. It is recommended to use 1.0-1.5 ml/kg b.w. of the 0.25% solution. If there are scars, adhesions as well as marked swellings at the operative site, it is advised not to use I.V.R.A. because of the greater risk of failure. The low postanaesthetic tendency for swelling and the extension of the operative site to the distal third of the upper arm are additionally stressed. Clinically relevant side effects were not observed.

Adolescent↗
PubMed1979

Computerized cranial tomography in Wilson disease.

Hepatolenticular degeneration (Wilson disease) is suspected by the clinical picture and confirmed by characteristic laboratory demonstration of impaired copper metabolism. Three patients with Wilson disease involving the basal ganglia were shown to have abnormalities on computerized tomography (CT) scan, whereas four other patients without signs of cerebral involvement had normal brain scans. Wilson disease may be added to the long list of diseases to which the EMI scan may make a useful diagnostic contribution.

Adult↗