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Biomedical subjects

J J Lokich

Publications and source records attributed to J J Lokich.

At least 37 records · Page 2Linked to original sources
PubMed1990

Very low doses of warfarin can prevent thrombosis in central venous catheters. A randomized prospective trial.

OBJECTIVE: To determine whether very low doses of warfarin are useful in thrombosis prophylaxis in patients with central venous catheters. DESIGN: Patients at risk for thrombosis associated with chronic indwelling central venous catheters were prospectively and randomly assigned to receive or not to receive 1 mg of warfarin, beginning 3 days before catheter insertion and continuing for 90 days. Subclavian, innominate, and superior vena cava venograms were done at onset of thrombosis symptoms or after 90 days in the study. RESULTS: One hundred twenty-one patients entered the study, and 82 patients completed the study. Of 42 patients completing the study while receiving warfarin, 4 had venogram-proven thrombosis. All 4 had symptoms from thrombosis. Of 40 patients completing the study while not receiving warfarin, 15 had venogram-proven thrombosis, and 10 had symptoms from thrombosis (P less than 0.001). There were no measurable changes in the coagulation values assayed due to this warfarin dose, except in occasional patients who had become anorectic because of their disease or chemotherapy. CONCLUSIONS: Very low doses of warfarin can protect against thrombosis without inducing a hemorrhagic state. This approach may be applicable to other groups of patients.

Adult↗
PubMed1990

Improved cancer chemotherapy. Benefits of delivery by infusion.

Chemotherapy delivered by infusion has developed in the last decade, primarily as a consequence of advances in technology but perhaps also because of increasing scientific understanding of pharmacology and tumor cell kinetics. Although few prospective, randomized trials have compared infusion-delivery with bolus-delivery schedules, those that have been performed have found that the infusion schedule provides at least a comparable response rate while improving drug toxicity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Secondary uncommon solid neoplasms in cured Hodgkin's disease and follow-up of the original B-DOPA chemotherapy patient group.

Three patients with Stage III or IVB Hodgkin's disease were cured with MOPP (regimen of nitrogen mustard, Oncovin, prednisone, and procarbazine) and/or B-DOPA (regimen of bleomycin, dacarbazine, Oncovin, prednisone, and Adriamycin). One had also received prior mantle radiation. After 13, 15 and 18 years in complete remission, three unusual solid tumors were diagnosed. One patient presented with a T3N2M0 epidermoid carcinoma of the soft palate; the second patient developed a T2N1M0 epidermoid carcinoma of the anus. The third patient developed a meningeal sarcoma that was metastatic to the lungs. Two additional patients, both of whom received MOPP and B-DOPA, died with more common tumors (esophageal and renal cell) at 7 and 10 years in association with recurrent Hodgkin's disease. Uncommon tumors may develop after long intervals following treatment for Hodgkin's disease and early detection requires diligent and persistent follow-up. The retrospective review of long-term survivors of the original B-DOPA regimen is of particular interest in that four of seven such patients developed solid tumors at 7, 10, 13, and 15 years. These patients had all received MOPP chemotherapy and six of seven had received radiation as well. The possibility of delayed solid tumors developing, particularly in patients having received both MOPP and B-DOPA or the related ABVD (regimen of Adriamycin, bleomycin, vinblastine, and dacarbazine) program, is of some concern.

Adult↗
PubMed1989

A phase I study of thiotepa administered by short-term and protracted continuous intravenous infusion.

Forty-five patients received escalating dose rates of continuous infusion thio-triethylene thiophosphoramide (TEPA) for either five (26 patients) or 28 (19 patients) days. Dose rate limiting toxicity for the 5-day infusion was myelosuppression with leukocyte and platelet nadirs on days 21 and 28, respectively. The nadir was influenced by the presence and degree of liver disease. The optimal dose rate for 5-day infusion in the absence of liver disease was 12 mg/m2/d and was reduced to 8 mg/m2/d in patients with major liver disease. Dose rate limiting toxicity for the protracted 28-day infusion was leukopenia. The optimal dose rate for the 28-day infusion was 4 mg/m2/d. Pharmacologic studies included determination of plasma steady state concentrations (CSS) of thio-TEPA and TEPA. Dose rates up to 10 mg/m2/d produced thio-TEPA and TEPA CSS below the levels of detection of available analytical methodology, except in three patients infused at dose rates of 1, 2, and 4 mg/m2/d, respectively.

Adult↗
PubMed1989

Free-standing cancer centers: rationale for improving cancer care delivery.

Free-standing cancer centers (FSCC) represent a growing trend in cancer care delivery within community practice. The critical components to FSCC are multidisciplinary cancer care, a complete menu of direct care and support services, a commitment to clinical trials and clinical investigation, and a comprehensive program for quality assurance. The advantages of FSCC to the community, to hospital programs, to the practicing surgical, medical, and radiation oncologists, and to the third-party carriers, including health maintenance organizations, are detailed. The development of an FSCC depends on the resolution of issues of (a) competition (between hospitals, hospitals and physicians, therapeutic disciplines, regional comprehensive cancer centers and FSCCs) and (b) concerns about conflict of interest. The ideal model of FSCC may well be represented by the joint venture of community hospital(s) and the community oncologists.

Ambulatory Care Facilities↗
PubMed1989

Clinical pharmacology of continuous infusion doxorubicin.

Fifteen patients were studied during short-term (5 days at 10-15 mg/m2/day) or long-term (5-104 days at 3 mg/m2/day) doxorubicin infusion. Levels of doxorubicin and metabolites in serum and 24-h timed urine collections were determined by high-performance liquid chromatography. Quantifiable anthracycline levels were identified in serum of 5 of 6 patients (6 courses) receiving drug at 10 mg/m2/day. In 5 courses, total anthracycline levels were 10-80 ng/ml, whereas levels as high as 370 ng/ml were observed in a patient with hepatorenal failure. No detectable serum levels of anthracycline were seen in patients receiving long-term doxorubicin therapy. Although analysis of 24-h timed urine collections revealed that doxorubicin was the predominant anthracycline, the extent of urinary elimination showed considerable interpatient variation (1.0-52.5% of the infused dose/24-h period on the short-term protocol and 5.3-57.2%/24-h period on the long-term protocol). Metabolic processing of doxorubicin administered by continuous infusion was found to be similar to that of drug given by bolus administration and showed no change in pattern with time. However, a greater variability in serum and urinary anthracycline levels was seen among patients on infusion schedules than has been noted with bolus drug treatment.

Doxorubicin↗
PubMed1989

A prospective randomized comparison of continuous infusion fluorouracil with a conventional bolus schedule in metastatic colorectal carcinoma: a Mid-Atlantic Oncology Program Study.

One hundred seventy-nine patients with advanced measurable colorectal cancer not previously treated with chemotherapy were entered into a prospective randomized clinical trial by the Mid-Atlantic Oncology Program (MAOP) to compare two schedules of delivery for single-agent fluorouracil (5-FU). The "standard" treatment was a schedule commonly employed in clinical practice, namely, a daily bolus dose administered intravenously (IV) for five consecutive days and repeated at 5-week intervals. The investigational treatment was a continuous infusion of 5-FU administered 24 hours a day for a protracted time (10 weeks or more). Both treatments were continued until the development of disease progression or unless interrupted for toxicity. Using stringent objective criteria requiring independent confirmation of x-ray or scan-documented response, the tumor response rate reached 7% (six of 87) for the bolus arm and 30% (26 of 87) for the infusion arms (P less than .001). Toxicity was substantially different for the two arms with major leukopenia observed only on the bolus arm, 22% developing grade 3 (severe) or grade 4 (life-threatening) leukopenia with four sepsis-related deaths. Hand-foot syndrome was observed only in the infusional arm, requiring treatment interruptions and dose reductions in 24% of patients, but with little impact on quality of life. In spite of the major difference in objective response rate, overall survival for the two groups was comparable. Administration of 5-FU as a continuous infusion for protracted periods clearly improves the therapeutic index for this agent in patients with advanced colon cancer with respect to response rate and reduced toxicity. This schedule appears workable in the community setting and yields response rates similar to those reported for 5-FU with high-dose leucovorin, but without the gastroin testinal toxicity profile of the latter combination.

Adenocarcinoma↗
PubMed1987

Sequential infusional 5-fluorouracil followed by concomitant radiation for tumors of the esophagus and gastroesophageal junction.

Thirteen patients with esophageal or gastroesophageal tumors with regional disease only were treated with sequential combined therapy. Weeks 1 to 6 continuous (24 hours) infusion 5-fluorouracil (5-FU) 300 mg/m2/d; weeks 6 to 10 or 12 infusional 5-FU administered concomitantly with radiation to the primary tumor site using standard fractionation with a cumulative median dose of 5000 rad; range 4400 to 6900 rad. Surgery was performed in five patients. All patients were evaluable for assessing response to the initial 5-FU infusion and 11/13 patients demonstrated tumor regression. Of 12 evaluable patients subsequently receiving combined infusional 5-FU and concomitant radiation, all 12 achieved complete clinical (10) or pathologic (two) tumor regression. Two of five patients having surgical resection had no pathologic evidence of tumor. All patients had relief of dysphagia within 1 week of initiating chemotherapy. Acute complications of therapy included stomatitis (two patients); hand-foot syndrome (two patients), and subclavian vein thrombosis (two patients). Stricture requiring periodic dilation occurred in three patients, and one patient developed a tracheoesophageal fistula at 36 months. Local control was maintained in 12/13 evaluable patients. Four of 13 patients were alive and without disease at 12 to 46 months. Nine patients died of distant metastases at 6 to 40 months. Median survival for the whole group was 16 months. Ten of the 13 patients (77%) survived for more than 1 year and 3/13 (22%) survived more than 3 years. This pilot study demonstrates the activity of 5-FU administered on an infusion schedule in both squamous and adenocarcinoma of the esophagus and the capacity to deliver infusional 5-FU throughout standard fractionation radiation. The local control and survival data may provide a basis for expanded Phase II trials, and a comparative trial against surgery alone might also be justified.

Aged↗
PubMed1987

Alpha-fetoprotein associated with islet cell tumors.

Elevated serum levels of alpha-fetoprotein (AFP) (100-1,000 ng/ml) were found in three patients with islet cell tumors. Serial levels correlated with progression of disease, suggesting that AFP could be a useful tumor marker substance for islet cell tumors. Survey sera from an expanded pool of 23 patients with islet cell tumors and nine with carcinoid tumors did not identify additional cases, however, suggesting that elevated AFP levels in these classes of Apudomas are uncommon. Nonetheless, the distinction from other AFP-producing tumors such as hepatocellular carcinoma is clinically important and warrants an awareness of the rare association of AFP with these tumors.

Adenoma, Islet Cell↗
PubMed1987

Biliary tract obstruction secondary to cancer: management guidelines and selected literature review.

Malignant biliary tract obstruction (MBTO) due to either primary biliary tract cancer or metastasis to the porta hepatis is a common clinical problem. The most common metastatic tumors causing MBTO in order of frequency are gastric, colon, breast, and lung cancers. Radiographic diagnostic procedures should proceed in a cost-effective sequence from ultrasonography, computerized tomography (CT), percutaneous transhepatic cholangiography (PTHC), and endoscopic retrograde pancreatography with the goal of establishing the site of the biliary tract obstruction. The identification of the site of obstruction could be established by ultrasound 70% to 80%, CT scan 80% to 90%, PTHC 100%, and endoscopic retrograde cholangiography (ERCP) 85%. Therapeutic intervention by radiographic decompression (PTHC or endoscopic prosthesis), surgical bypass, or radiation therapy with or without chemotherapy may be selectively used based on (1) the site of obstruction; (2) the type of primary tumor; and (3) the presence of specific symptoms related to the obstruction. ("Prophylactic" biliary tract decompression to prevent ascending cholangitis is not supported by the literature in that the frequency of sepsis in the face of malignant obstruction is small (in contrast to sepsis associated with stone disease). Furthermore, PTHC with drainage as a long-term procedure is associated with a substantial frequency of sepsis and is unnecessary and possibly problematic as a preoperative procedure simply to reduce the bilirubin level. The use of radiation therapy in conjunction with chemotherapy for patients not deemed suitable for a surgical bypass because of the presence of proximal obstruction is an important alternative to PTHC.

Algorithms↗
PubMed1987

Etoposide in combination with cytarabine, doxorubicin, and 6-thioguanine for treatment of acute nonlymphoblastic leukemia in a protocol adjusted for age.

Etoposide combined with cytarabine, doxorubicin, and 6-thioguanine was used to treat 34 patients with acute nonlymphoblastic leukemia (ANLL) in an age-adjusted protocol, with patients greater than 50 years old receiving fewer days of therapy. Complete remissions (CR) occurred in 85% of all patients (29 of 34 patients). Patients less than or equal to 50 years of age achieved a 94% CR rate (17 of 18 patients) compared to a 75% CR rate (12 of 16 patients) in older patients. Duration of remission was less for those greater than 50 years of age. The remission rate for primary ANLL was 86% (19 of 22 patients) and for secondary or relapsed ANLL was 83% (ten of 12 patients). Thus, this is effective therapy for primary and secondary or relapsed ANLL. When the days of therapy are reduced for older patients' age, the remissions are fewer and less durable.

Acute Disease↗
PubMed1986

Doxorubicin/vinblastine and doxorubicin/cyclophosphamide combination chemotherapy by continuous infusion.

Fifty-two patients received one of two doxorubicin (DOX)-based admixtures; DOX plus cyclophosphamide (CTX) or DOX plus vinblastine (VBL) administered as a continuous 24-hour infusion for protracted periods. Compatibility and stability of the two-drug admixture was established for a minimum of 7 days. Twenty patients on the DOX/CTX admixture were infused for a median of 20 days (range, 7-56 days). DOX/VLB was infused in 32 patients for a median of 18 days (range, 5-48 days). Dose limiting toxicity was leukopenia observed in 14/52 patients; 4/20 on DOX/CTX and 10/32 on DOX/VLB. Additional toxicities observed included stomatitis (15%) and subclavian vein thrombosis (23%). Tumor responses were observed in 11 patients, including 6/13 breast cancer; 2/2 hepatoma; 2/4 sarcoma and 1/1 ovarian cancer. Responses were relatively short-lived and no responses were noted in known anthracycline resistant tumors. Admixtures of chemotherapeutic agents represents a novel, but feasible, mechanism for delivery of multiple drugs with an infusion schedule and can be considered for Phase III comparative clinical trials.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Systemic infusional chemotherapy for liver metastasis: an improved schedule for 5-fluorouracil.

The clinical studies of infusion schedules for cancer chemotherapy have established that this schedule substantially alters the pattern of drug toxicity without necessarily compromising therapeutic effectiveness. Although increased tumor cell killing has not been definitively established, in at least two prospective comparative trials of 5-FU the infusion schedule was superior to bolus delivery in terms of response rate. It is possible that the infusion schedule may be the primary determinant of the effectiveness of hepatic arterial chemotherapy, and preliminary reports of prospective trials comparing systemic infusion with hepatic infusion do suggest that response rates for both routes are similar. An important consideration with regard to infusion schedules is establishing whether or not tumor cell resistance is augmented by the continuous exposure. Almost all chronic disease therapy necessitates maintaining adequate drug levels to ensure disease control including infections, seizure disorders, arthritis, and cardiovascular diseases. For cancer, the intermittent schedule of drug delivery has been dictated by the concept of the primacy of dose and the substantial toxicity associated with these agents. With the technological capability of providing an ambulatory setting for infusion chemotherapy and the substantial modification of toxicity, therapeutic regimens may be more cost effective with the constant infusion schedule.

Clinical Trials as Topic↗
PubMed1986

Non-human primate (baboon) anti-carcinoembryonic antigen antibody infusion in patients with metastatic adenocarcinoma. A phase I study.

A total of 14 patients with advanced visceral carcinoma which produced carcinoembryonic antigen (CEA) were treated in a Phase I study with IV infusion of affinity purified baboon anti-CEA antibody (dosage range from 0.1 to 2 mg/kg body weight). In all 14 patients, the antibody infusion caused a decrease (26% to 97%) in the plasma level of CEA. The degree of decrease depended upon the patients initial CEA level and the amount of antibody given. In 12 of the 14 patients "free" circulating antibody was observed. The plasma half-life of the antibody ranged from 0.7 to 21 h and the duration of detectable free antibody ranged from 3 to 216 h postinfusion. No toxicity was observed for the dosage range of antibody tested. In 9 of the 14 patients a low titer anti-baboon antibody response occurred between 14 and 28 days postinfusion. No clinical regression of carcinoma was documented. In 7 of the 14 patients disease remained stable during the 28-day study period. By the end of the 28-day study period plasma CEA levels had returned to at least the preinfusion level in 11 of the 14 patients.

Adenocarcinoma↗
PubMed1986

Fluoxymesterone stimulation of tumor marker secretion in patients with breast carcinoma.

The gross cystic disease fluid protein of 15,000 MW (GCDFP-15) has been demonstrated to be a circulating glycoprotein tumor marker for breast carcinoma in approximately 40% of patients with advanced disease. A recent retrospective analysis of plasma GCDFP-15 levels in patients with advanced breast cancer suggested that androgen therapy could cause significant increases in plasma levels in the absence of disease progression. In order to evaluate the frequency, time course, and intensity of the androgen effect on GCDFP-15 production, a prospective study was initiated. Twenty-nine patients with stage IV breast carcinoma were treated with fluoxymesterone (20 or 30 mg/d). Plasma levels of GCDFP-15 and carcinoembryonic antigen (CEA) were measured by radioimmunoassay before and at various times during therapy. By day 6 of therapy, plasma GCDFP-15 had increased significantly (p = 0.03) from a mean basal level of 58 +/- 12 ng/ml to 160 +/- 60 ng/ml. By contrast, the mean CEA levels in the same patients increased only from 36 +/- 14 ng/ml. The distribution of percent increases in plasma GCDFP-15 was not uniform, but patients with high (greater than 82 ng/ml) basal levels had marked (greater than or equal to 75%) increases in 6/6 (100%) cases, whereas patients with low (less than 30 ng/ml) basal levels had similar increases in only 2/15 (13%) cases. Urinary excretion of GCDFP-15 usually paralleled the increases in plasma levels of the glycoprotein during the first six days of therapy. A linear correlation between percent change in plasma and percent change in urinary GCDFP-15 was demonstrated. A permanent cell line of human breast carcinoma, T47-D, was stimulated to secrete GCDFP-15 in vitro by androgen, but not by estrogen. From these data, we conclude that androgens can specifically stimulate secretion of GCDFP-15 by breast carcinoma tissue in most patients with elevated plasma levels of GCDFP-15, and in some patients with normal levels. The stimulation occurs within days and is not associated with clinical signs of tumor growth.

Apolipoproteins↗
PubMed1986

Radiologic manifestations of small-bowel toxicity due to floxuridine therapy.

Floxuridine (5-FUDR) is an antipyrimidine used in the treatment of metastatic colorectal carcinoma. Bowel toxicity, manifested predominantly by diarrhea and abdominal pain, is one of the main complications of 5-FUDR therapy. Six patients who had received 5-FUDR infusion either by hepatic arterial or systemic intravenous routes subsequently developed severe diarrhea and were evaluated by small-bowel series. Radiographic changes were largely confined to the ileum. In four of six patients, the entire ileum or its more distal part was markedly narrowed. In the other two patients, changes consisted of thickening or effacement of the mucosal folds in the distal ileum. The symptoms of all six patients resolved after discontinuation of 5-FUDR therapy. This was accompanied by improvement in the radiographic appearance of the ileum in three patients who underwent a subsequent small-bowel series. The finding of reversible ileal changes, particularly extensive or segmental narrowing, seems to be a characteristic radiographic feature of bowel toxicity due to infusional 5-FUDR delivered by either the intraarterial or the systemic route.

Aged↗
PubMed1985

A phase I and pharmacology study of continuous-infusion low-dose methotrexate administration.

Continuous intravenous infusion of methotrexate (MTX) was evaluated in a Phase I study designed to establish the optimal dose rate to provide a minimum of 28 days of constant 24-hour drug exposure. Twenty-six courses were administered to 21 patients at dose rates of 0.75 mg/M2/day to 3 mg/M2/day. Dose-limiting toxicity was predominantly stomatitis at the highest dose rates. Thrombocytopenia (platelet count less than 100,000) without leukopenia developed in 8 of 26 courses at the lower dose rates, with or without stomatitis, and was rapidly reversible. Serial blood levels revealed detectable serum MTX concentrations at all dose rates delivered with mean MTX concentrations varying from 12.8 nM at 0.75 mg/M2/day to 140 nM at 2.5 mg/M2/day. Total-body clearance of MTX approximated renal creatinine clearance. The recommended dose rate for continuous infusion of methotrexate is 0.75 mg/M2/day for 28 days, and for shorter durations (less than or equal to 14 days), the optimal dose rate is 1.5 mg/M2/day. The continuous-infusion schedule for MTX, therefore, results in a substantial decrease in the delivered dose compared with that achieved with a bolus schedule.

Adult↗