Biomedical subjects

L Boros

Publications and source records attributed to L Boros.

At least 19 recordsLinked to original sources

PubMed2001

Weekly paclitaxel in advanced non-small cell lung cancer.

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is one of the most commonly used agents in treating patients with locally advanced and metastatic non-small cell lung cancer (NSCLC). It is usually given once every 3 weeks. We have evaluated paclitaxel given once per week for 3 weeks every 4 weeks for patients with recurrent or metastatic NSCLC. Two consecutive studies using weekly paclitaxel were performed. The first study was a dose-escalation study with paclitaxel beginning at 50 mg/m(2) days 1, 8, and 15 every 4 weeks. Subsequent dose escalation was performed with 10 mg/m(2) increments per week. The second phase II study used paclitaxel at 80 mg/m(2) days 1, 8, and 15 every 4 weeks. The phase I study showed that the maximum tolerated dose was 90 mg/m(2)/wk for 3 weeks with 1 week off. The efficacy and side effects of both phase I and II were quite similar; therefore, the results were combined. Seventeen patients were in the phase I and 30 patients in the phase II study. The mean age was 72 years. Twenty-three patients had Eastern Cooperative Oncology Group performance status of 2 and 16 patients had received prior chemotherapy. One complete and 13 partial responses were observed with response duration ranging from 1 to 18+ months. Overall response rate was 30% (95% confidence interval, 18.5% to 42%). Overall median survival was 184 days. Grade 3/4 neutropenia was 8.5%, grade 3/4 infections was 6.4%, and grade 2 peripheral neuropathy was also 6.4%. Hyperglycemia with random blood sugar levels greater than 250 mg/dL was 6.4% and grade 3 fatigue was 4.3%. In general, treatment was well tolerated. In the best prognostic group of 16 patients without prior chemotherapy and with performance status 0 to 1, the response rate was 37.5% with a 1-year survival rate of 44% and median survival of 305 days. Prior chemotherapy, poor performance status, age higher than 70 years, and male gender carried a worse prognosis. In both phase I and II studies we observed limited myelosuppression, peripheral neuropathy, and constitutional symptoms. Weekly paclitaxel, delivered at our schedule, is an active and well-tolerated regimen. The role of weekly paclitaxel in NSCLC should be better defined in future randomized studies.

Aged↗

PubMed1999

Ifosfamide, carboplatin and etoposide (ICE) in metastatic and refractory breast cancer.

Twenty-five patients with metastatic breast cancer were treated with ICE after failure of previous chemotherapy. Their median age was 50 years (range 36-73). All but 1 patient had multiple sites of metastases. Nineteen (76%) patients had undergone two or more chemotherapy regimens for metastatic disease prior to ICE. The performance status (PS) of the patients was Eastern Cooperative Oncology Group (ECOG) 0:6; 1:12; 2:5; 3:2. Ifosfamide 1.25 g/m(2) over 3 h D1-3 along with mesna, etoposide 80 mg/m(2) D1-3 and carboplatin 300 mg/m(2) D1 were given every 3 weeks. We observed a partial response in 10 patients (40%, 95% confidence interval 21-62%). The response duration ranged from 1 to 15 months with a median duration of 4.5 months. The survival of all 25 patients ranged from 10 days to 25 months, with a median of 9 months. All 25 patients were evaluable for toxicity. Thirteen patients (52%) experienced grade 4 hematological toxicity, which improved after growth factor support. Four patients had leukopenic fever, 1 had gram-negative sepsis, while 2 had Clostridium difficile enterocolitis and another had herpes zoster reactivation. Four patients (16%) experienced grade 3-4 gastrointestinal (G-I) toxicity. No hepatic or renal toxicity was observed (1 patient had microscopic hematuria). One patient died of G-I bleed, and another patient died at home of undetermined cause. We conclude that ICE is an effective salvage regimen in metastatic and refractory breast cancer, even in heavily pretreated patients, and is a tolerable treatment when used with growth factor.

Adult↗

PubMed1998

[Botulism. Summary based on six cases].

Botulism is a rare neuroparalytic disease caused by neurotoxins of Clostridium species. In Hungary it most commonly occurs as a foodborne illness with ocular and bulbar paralysis, muscle weakness and gastrointestinal symptoms. Six cases of botulism were observed by the authors, first in 1993 five members of a family, then in 1997 a patient with sporadic illness. The diagnosis was confirmed by toxin tests in addition to the symptoms and food history. Recognition of the epidemiologic associations proved very useful in the confirmation of outbreak-related cases. The illness was moderately serious at three patients and mild at two patients. One of the patients had a cirrhosis of the liver, and her status became critical because of the repeated bleeding from oesophagus varicose vein. The patient with sporadic illness had a serious gastric dilatation and palsy of bowels causing paralytic ileus at the start of the illness. The symptoms regressed slowly, roughly in three weeks, at all patients. Death did not happened. After the case reports the authors review the disease-microorganism, toxin, clinical entities, incidence, symptoms, diagnosis, differential-diagnosis, and finally the treatment.

Acetylcholine↗

PubMed1997

Dose-escalation study of weekly 1-hour paclitaxel administration in patients with refractory cancer.

To evaluate the safety and efficacy of weekly low-dose paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in patients with refractory cancer, participating subjects received standard prophylactic medication followed by intravenous paclitaxel once a week for 3 weeks every 4 weeks. The 50-mg/m2 starting dose was increased by 10 mg/m2 for every five patients, as long as no dose-limiting toxicity had occurred in more than two of five patients treated at the preceding level. Eligibility criteria included metastatic and refractory malignant disease; an Eastern Cooperative Oncology Group performance status of 0, 1, or 2; and adequate hematologic, hepatic, and renal functions. Of 30 patients treated and evaluable for toxicity, 25 were evaluable for response. The majority of patients tolerated the treatment very well. In a total of 114 cycles, the worst toxicities observed were leukopenia (one grade 4, two grade 3), granulocytopenia (one grade 3, one grade 4), anemia (one grade 3, two grade 2), and infection (one grade 5, one grade 3). Three patients had grade 2 gastrointestinal toxicity and three had grade 1 peripheral neuropathy. Only one dose-limiting toxicity, at 100 mg/m2, has occurred. This patient died of bilateral pneumonia with neutropenia. We have observed partial responses in seven of 12 patients with breast cancer and three of eight with non-small cell lung cancer. The study remains open at the current dose level of 100 mg/m2/wk. Weekly low-dose paclitaxel is well tolerated and efficacious. Further phase II studies are warranted, to continue evaluation of this schedule of paclitaxel either alone or in combination with other drugs active in paclitaxel-responsive diseases.

Adult↗

PubMed1996

Ifosfamide, carboplatin, etoposide, and paclitaxel chemotherapy: a dose-escalation study.

Ifosfamide, carboplatin, cisplatin, etoposide, and paclitaxel are chemotherapeutic agents active in treating many malignant diseases. The ICE combination (ifosfamide/carboplatin [or cisplatin]/etoposide) has been studied in breast cancer, small cell and non-small cell lung cancer, testicular cancer, lymphoma, and other malignancies with promising results. We conducted a dose-escalation study of paclitaxel in combination with ICE (ICE-T) to evaluate the toxicity and define the maximum tolerated dose of paclitaxel. To date, 24 patients have been treated with ICE-T. Patients had to have no or minimal prior chemotherapy, an Eastern Cooperative Oncology Group performance status of 0 or 1, and adequate bone marrow, liver, and kidney function. The doses of ICE were as follows: ifosfamide 1.25 g/m2/d days 1 to 3, carboplatin 300 mg/m2 day 1, and etoposide 80 mg/m2/d days 1 to 3. Paclitaxel was given at a dose of 120 mg/m2 to five patients, 135 mg/m2 to five patients, 150 mg/m2 to three patients, and 175 mg/m2 to 11 patients. All patients received granulocyte colony-stimulating factor support. The most common side effect was neutropenia. Grade 4 neutropenia and thrombocytopenia occurred during 34% and 20% of 94 cycles, respectively, with leukopenic fever occurring during 14% of cycles. No treatment-related death or sepsis occurred due to brief nadir durations of 3.5 days for neutropenia and thrombocytopenia. Other toxicities were mostly mild to moderate and did not require dose modification, although alopecia was universal. Nine patients (100%) with metastatic breast cancer and four (67%) with soft tissue sarcoma have attained documented objective responses with four complete remissions (one breast cancer and three sarcoma patients). The maximum tolerated dose of paclitaxel has not yet been defined, and the study is ongoing. In conclusion, this pilot study showed that ICE-T is safe and tolerable. The response to ICE-T is encouraging and warrants further study with this regimen.

Adult↗

PubMed1995

Paclitaxel by 3-hour infusion followed by 96-hour infusion on failure in patients with refractory malignant disease.

To explore the potential therapeutic differences between 3- and 96-hour infusions of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in patients with refractory malignant diseases, we conducted a phase II study in which patients were treated first with paclitaxel 135 mg/m2 by 3-hour infusion. If patients did not respond or relapsed after response, they were then treated by 96-hour infusion of paclitaxel at the same dose. Patients with metastatic or incurable breast, ovarian, lung, head/neck carcinomas, and lymphoma were eligible. They were required to have an Eastern Cooperative Oncology Group performance status of 2 or better and adequate hematologic, hepatic, and renal functions. In 22 patients entered thus far, we have observed one partial response in 10 lung cancer patients treated by 3-hour paclitaxel and one partial response in six patients treated by 96-hour infusion. Four partial responses were observed with 3-hour paclitaxel alone in nine breast cancer patients, while three partial responses occurred in five patients with 96-hour infusion after the 3-hour infusion failed. Nonhematologic toxicities such as fatigue, peripheral neuropathy, and mucositis occurred more commonly in the 96-hour infusion group. Our preliminary results suggest (1) that 3-hour infusion of paclitaxel is active against refractory breast cancer, (2) that 96-hour infusion of paclitaxel can induce partial response in breast cancer that was refractory to 3-hour treatment of paclitaxel, and (3) that more studies are needed to define the optimal treatment schedule of paclitaxel.

Adult↗

PubMed1995

Phase I study of escalating doses of paclitaxel (Taxol) with fixed doses of ifosfamide, carboplatin, and etoposide.

The combination of ifosfamide (with mesna uroprotection), carboplatin, and etoposide (ICE) has demonstrated activity in a variety of cancers. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), a dipertene compound extracted from the Pacific yew Taxus brevifolia, appeared a good candidate for study as an addition to the ICE regimen (ICE-T) because of its broad antitumor activity, its unique mechanism of action, and its toxicity profile, which was not expected to impact the ICE regimen adversely. In a phase I study, we evaluated the impact of adding escalating doses of paclitaxel (120 mg/m2, 135 mg/m2, 150 mg/m2, and 175 mg/m2) to the ICE regimen in 13 previously untreated (with two exceptions) patients with breast cancer, sarcoma, lung cancer, and adenoid cystic carcinoma. In general, ICE-T was well tolerated with some myelosuppression observed. Responses were seen at all dose levels. To date, the maximal tolerated dose of paclitaxel has not been reached; we are currently administering 175 mg/m2.

Adult↗

PubMed1995

Ifosfamide/carboplatin/etoposide chemotherapy in patients with metastatic non-small cell lung cancer.

We have evaluated the combination of ifosfamide, carboplatin, and etoposide (ICE) along with mesna in 46 patients with stage IV non-small cell lung cancer. Treatment consisted of ifosfamide (1.25 g/m2/d with mesna) and etoposide (80 mg/m2/d) given intravenously on days 1 to 3 and carboplatin (300 mg/m2) given intravenously on day 1 every 4 weeks. Eligibility criteria included measurable disease; adequate hematologic, hepatic, and renal functions; no prior chemotherapy; and an Eastern Cooperative Oncology Group performance status (PS) of 0 to 3. Two patients were lost to follow-up and one had received prior chemotherapy, leaving 43 patients evaluable for response and toxicities. There were 27 male and 16 female patients. Twenty-three patients had a PS of 0 or 1 and 20 had a PS of 2 or 3. Eighteen patients had received prior radiotherapy. There were two complete responses and nine partial responses. The response rate was 35% in PS 0 or 1 patients and 15% in PS 2 or 3 patients. The most frequent toxicity was myelosuppression; 44% of patients experienced grade 3 or 4 leukopenia and 14%, grade 3 or 4 thrombocytopenia. Patients receiving prior radiation were significantly more prone to develop leukopenia (P = .01). Five patients developed leukopenic fever, and three died of sepsis. Gastrointestinal toxicities were mostly mild. No neurologic or genitourinary toxicities were observed. The median length of survival was 209 days for patients with a PS of 0 or 1 and 123 days for the entire group. The 1-year survival rate was 22% and 19%, respectively, in these two patient subgroups. ICE is an active regimen in patients with metastatic non-small cell lung cancer and a good PS. Myelosuppression is the major dose-limiting toxicity. Hematopoietic growth factors may be indicated in subsequent studies, especially in patients who had prior radiation therapy. The therapeutic effect of ICE on patients with a poor PS remains unsatisfactory and requires further investigation.

Adult↗

PubMed1994

Phase II study of ifosfamide, carboplatin, and etoposide in patients with advanced non-small cell lung cancer.

This study was to define the efficacy of ifosfamide, mesna, carboplatin, and etoposide (ICE) in patients with metastatic non-small cell lung cancer (NSCLC). From September 1990 to October 1991, 33 patients were treated with ifosfamide/mesna 1.25 g/m2/day and etoposide 80 mg/m2/day intravenously from days 1 to 3, and carboplatin 300 mg/m2 on day 1 every 4 weeks. There were 20 male patients and 13 females. The median age was 65 (range: 38-79). Seventeen patients had a performance status (PS) of 0 or 1, and 16 had a PS of 2 or 3. All had measurable diseases. Nine had initial treatment for localized disease with concurrent radiation, 5-fluorouracil, and interferon-alpha 2b and four had radiation only. None had received chemotherapy for metastatic disease. There were nine partial responses (PR) (27.3%, 9/33) with a median response duration of 8 months (range: 2-16 months). Five patients had stable diseases (SD), which lasted for 3, 6+, 7+, 10+, or 13.4 months. The median survival was 8 months for PR and SD and 4 months for the entire group. Patients with PS of 2 or 3 were less likely to respond (18.8% vs 35.3%) and had a shorter median survival (2.7 months vs 6 months) than patients with better PS. Dose-limiting toxicity was myelosuppression. Seventeen (51.5%, 17/33) patients developed grade III-IV leukopenia with four septic episodes and three septic deaths. Grade III or IV thrombocytopenia was seen in five patients. Patients with prior radiation were significantly more prone to develop leukopenia (P < .005). Gastrointestinal toxicity was mostly mild. No neurologic or genitourinary toxicity was observed. In conclusion, ICE is active in patients with advanced NSCLC and good PS. Besides myelosuppression, it is well tolerated. Further study is indicated to evaluate if granulocyte-colony stimulating factor can reduce myelosuppression from ICE in good PS patients.

Adult↗

PubMed1992

Distribution characteristics of mitoxantrone in a patient undergoing hemodialysis.

The pharmacokinetic profile of mitoxantrone in a patient undergoing hemodialysis is described. Significant characteristics of our patient included lymphoma with liver involvement, tumor lysis syndrome, renal and hepatic failure. Combination chemotherapy consisted of mitoxantrone, vincristine, and cyclophosphamide. Mitoxantrone plasma samples were obtained prior to dosing and at 0, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.5, 7.0, and 12 h after the intravenous infusion of a 17-mg dose over 20 min. Serum concentrations were determined by high-performance liquid chromatography. The serum concentration versus time curve was consistent with a three-compartment model. However, rebounds in serum drug concentrations were detected during the last portion of dialysis and after its completion. The gamma elimination half-life could not be determined due to the continued detection of rebounds in drug concentrations throughout the postdialysis sampling period. The alpha and beta distribution phases did not appear to be affected by hemodialysis. The peak mitoxantrone concentration fell within the reported range. Mitoxantrone does not appear to be eliminated by hemodialysis, and dose adjustments are not needed in patients undergoing this procedure.

Aged↗

PubMed1991

13-cis-retinoic acid in the treatment of elderly patients with acute myeloid leukemia. A phase II pilot study of the Eastern Cooperative Oncology Group.

The management of acute myeloid leukemia in the elderly (65 years and older) is unsatisfactory because of poor patient tolerance of standard myeloablative chemotherapy. The authors conducted a Phase II study to evaluate the effectiveness and toxicity of 13-cis-retinoic acid (CRA) in the therapy of elderly patients with acute myeloid leukemia (AML). Patients presenting with leukocyte counts less than 20,000/microliters were treated with CRA alone. Those with leukocyte counts of 20,000/microliters or greater were pretreated with hydroxyurea, followed by CRA. Twelve of 18 patients received at least 4 weeks of CRA and were thus considered evaluable for toxicity and response. No objective responses were observed. Cis-retinoic acid administration was well tolerated; only modest dermatologic, musculoskeletal, and gastrointestinal toxicity was observed. Alternative therapeutic strategies should be investigated in this subpopulation of AML patients.

Aged↗

PubMed1991

Essential role of cholecystokinin in pancreatic regeneration after 60% distal resection in rats.

The essential role of cholecystokinin (CCK) in pancreatic regeneration after pancreatitis or resection has been supposed, but not yet clearly demonstrated. In rats, 6-8 weeks after 60% distal resection of the pancreas a gradual increase in pancreatic weight and contents of DNA, protein, trypsin, chymotrypsin and amylase, occurred (there was no increase in lipase); Pancreatic regeneration stopped thereafter. Nonparallel increases in enzyme values were similar to those seen after CCK administration. Indeed, basal CCK levels increased significantly by the 6th week and declined thereafter. A one month s.c. administration of CCK-octapeptide (CCK-8) (3 x 300 ng/kg/d) accelerated regeneration in the first month, but it had almost no effect during the second or third postoperative months. A two week s.c. administration of a specific CCK antagonist, CR 1409 (3 x 4 mg/kg/d) totally prevented regeneration by the fifth and sixth weeks, but did not diminish pancreatic weight or DNA and protein contents during the first two weeks. Alcohol administration (12 g/kg/d) reduced CCK release and prevented pancreatic regeneration during the three-month experimental period. These data indicate that CCK has an essential role in pancreatic regeneration and that the deleterious effect of alcohol on regeneration involves inhibition of CCK release.

Amylases↗

PubMed1990

Pharmacokinetics of very high-dose oral melphalan in cancer patients.

The pharmacokinetics and systemic availability of melphalan after high-dose oral administration with and without 1,3-bis(2-Chloroethyl)-1-nitrosourea (BCNU) or etoposide were examined in three patients undergoing autologous bone marrow transplantation. Patient 1 (advanced melanoma) received melphalan at 80 mg/m2/day p.o. on days -6, -5, and -4, followed by BCNU at 300 mg/m2/day i.v. on days -3, -2, and -1 prior to bone marrow transplantation. Patient 2 (advanced colon carcinoma) received melphalan at 75 mg/m2/day p.o. on days -3, -2, and -1. Patient 3 (advanced refractory lymphoma) received etoposide at 800 mg/m2/day i.v. on days -7, -5, and -3, followed by melphalan at 157 mg/m2/day p.o. on days -2 and -1. Melphalan was administered as a bolus oral dose, using 2-mg tablets. Blood samples were collected at 0, 5, 10, 15, 30, and 45 min and 1, 2, 3, 4, 6, 8, 12, and 24 h after each dose of melphalan. Peak plasma melphalan concentrations in the three patients ranged from 0.354 (patient 2) to 1.768 micrograms/ml (patient 1). Plasma melphalan concentration X time products (C x Ts) showed extreme variability in one patient (patient 2), ranging from 0.76 to 4.48 micrograms.h/ml. To determine the relative systemic availability of orally administered melphalan, i.v. C X Ts proportional to the p.o. doses were extrapolated from previously reported i.v. bolus pharmacokinetic data. The p.o.:i.v. plasma C X T ratios for high-dose melphalan ranged between 0.09 (patient 3) and 0.58 (patient 2). Although these C X T data suggest a dose-response for orally administered melphalan, the systemic availability of these high p.o. melphalan doses was extremely variable, both within and between study patients. Thus, we cannot recommend the use of high-dose p.o. melphalan regimens in patients undergoing autologous bone marrow transplantation.

Adenocarcinoma↗

PubMed1989

Alcohol-induced chronic pancreatitis in rats after temporary occlusion of biliopancreatic ducts with Ethibloc.

Chronic obstructive pancreatitis-like histological and biochemical alterations were provoked in male Wistar rats with Ethibloc occlusion of the common bile duct and the main pancreatic ducts. After the disappearance of the glue from the ducts, a gradual and almost total recovery was demonstrated during a 2-month observation period. About 12 g/kg of alcohol (20% vol/vol) given daily by gastric intubation and ad libitum intake inhibited the recovery of pancreatic weight and enzyme contents in the occluded rats, and within a 2-month period chronic calcifying-type pancreatitis became evident with some signs of remaining obstructive pancreatitis-like lesions. Cessation of alcohol administration after 2 months resulted in a recovery of pancreatic weight and enzyme contents, although morphological regeneration was less pronounced and calcification remained visible in some rats. A 50% raw soy flour diet provoked some further changes in the proportion of enzymes without any supplementary increases of pancreatic weight and protein content. This animal model of chronic pancreatitis demonstrates that chronic obstructive and calcifying pancreatitis can appear together and earlier if the etiological factors act in combination. Suppression of pancreatic regeneration by alcohol seems to be necessary to maintain chronic pancreatitis-like lesions and to develop calcification.

Animals↗

PubMed1988

Leukemic dermal infiltrates as a complication of central venous catheter placement.

A leukemic dermal infiltrate at the site of a central venous catheter placement was the first manifestation of relapse in a 58-year-old woman in clinical remission of acute myelomonocytic leukemia. The patient developed a large hematoma around the site of an unsuccessful attempt to place a central venous (CV) catheter. Although the hematoma resolved completely by the time that complete remission was achieved, an indurated, erythematous mass subsequently developed, which when biopsied revealed leukemic cells in the dermis. The patient had a relapse in her peripheral blood shortly thereafter. The authors reviewed recent literature and their own experience with CV catheters and report on localized dermal relapse as a previously unpublished risk of CV catheter placement. They also speculate on the role of the dermis as a sanctuary for leukemic cells and a potential source for relapsing disease.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1988

Trisomy 5 as sole anomaly in acute lymphoblastic leukemia.

We present a case of B-cell acute lymphoblastic leukemia (ALL) in whose leukemic cells trisomy 5 (+5) was the only cytogenetic anomaly observed. This is the first report of +5 as the sole cytogenetic abnormality in ALL; two cases (one questionable) of acute nonlymphocytic leukemia with such a change have been reported. The findings are presented in relation to other cases with +5 as part of a more complicated cytogenetic picture in hematologic disorders.

Adult↗

PubMed1987

5-Fluorouracil and high-dose folic acid treatment for metastatic colon cancer.

Twenty-two patients with metastatic colorectal cancer were treated with a regimen of 5-fluorouracil 600 mg/m2 (maximum, 1.0 g) i.v./week and folic acid 140 mg/m2 i.v. given 1 h prior to the 5-FU. This study was undertaken in an attempt to confirm the in vitro finding that inhibition of thymidylate synthetase by 5-fluorouracil is prolonged by the presence of folates. There were four partial responses (18%) with mean duration 4 months. Dose-limiting toxicity was enteritis, seen in 12 patients (58%), and causing hospitalization in seven patients. Enteritis was shown to be due to the folic acid in most patients. Two patients died from leukopenia, enteritis, and sepsis. Mean serum folate levels at the time of 5-FU injection were 36 microM. This regimen is no more effective than 5-FU alone and has significantly more serious toxicity. Further investigation of this regimen is not recommended.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1987

Evaluation of CCNU and misonidazole in the treatment of advanced colorectal cancer.

Eighteen adult colorectal cancer patients, previously untreated with systemic chemotherapy, were given CCNU and MISO. One patient had an excellent partial response of pulmonary metastases, but the overall response rate was only 6%. Gastrointestinal toxicity was modest, hematologic toxicity was similar to what would have been predicted for CCNU alone, and there was no neurotoxicity detected. This Phase II study demonstrates that these two agents can be administered safely, but have no advantage over CCNU alone.

Adult↗