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Biomedical subjects

T E Spiro

Publications and source records attributed to T E Spiro.

At least 19 recordsLinked to original sources
PubMed2001

Subcutaneous enoxaparin once or twice daily compared with intravenous unfractionated heparin for treatment of venous thromboembolic disease.

BACKGROUND: Low-molecular-weight heparins administered subcutaneously once or twice daily have been reported to be as safe and efficacious as intravenous unfractionated heparin in the treatment of acute venous thromboembolic disease. OBJECTIVE: To determine whether subcutaneous enoxaparin administered once or twice daily is as effective as continuously infused unfractionated heparin in acute symptomatic venous thromboembolic disease. DESIGN: Randomized, controlled, partially blinded equivalence trial. SETTING: 74 hospitals in 16 countries. PATIENTS: 900 patients with symptomatic lower-extremity deep venous thrombosis, including 287 (32%) with confirmed pulmonary embolism. INTERVENTIONS: Initial therapy with dose-adjusted intravenous unfractionated heparin compared with subcutaneous enoxaparin at fixed dosages of 1.0 mg/kg of body weight twice daily or 1.5 mg/kg once daily. Long-term oral anticoagulation was started in all patients within 72 hours of randomization. MEASUREMENTS: Clinical end points assessed during a 3-month follow-up period. RESULTS: Equivalent efficacy was seen in the heparin group and both enoxaparin groups. Symptomatic venous thromboembolism recurred in 12 of 290 patients receiving unfractionated heparin (4.1%), 13 of 298 patients receiving once-daily enoxaparin (4.4%), and 9 of 312 patients receiving twice-daily enoxaparin (2.9%). Compared with unfractionated heparin, the treatment difference was 0.2% (95% CI, -3.04% to 3.49%) for once-daily enoxaparin and -1.2% (CI, -4.2% to 1.7%) for twice-daily enoxaparin. Incidence of major hemorrhage did not differ among the three treatment groups. Major hemorrhage occurred in 6 of 290 patients (2.1%) in the unfractionated heparin group, 5 of 298 patients (1.7%) in the once-daily enoxaparin group, and 4 of 312 patients (1.3%) in the twice-daily enoxaparin group. CONCLUSIONS: Subcutaneous enoxaparin once or twice daily is as effective and safe as dose-adjusted, continuously infused unfractionated heparin in the prevention of recurrent symptomatic venous thromboembolic disease.

Administration, Cutaneous↗
PubMed2001

Prolonged enoxaparin therapy to prevent venous thromboembolism after primary hip or knee replacement. Enoxaparin Clinical Trial Group.

BACKGROUND: Patients undergoing hip or knee joint replacement are at risk for venous thromboembolic complications for up to twelve weeks postoperatively. We evaluated the efficacy and safety of a prolonged post-hospital regimen of enoxaparin, a low-molecular-weight heparin, in this patient population. METHODS: Following elective total hip or knee replacement, 968 patients received subcutaneous enoxaparin (30 mg twice daily) for seven to ten days, and 873 were then randomized to receive three weeks of double-blind outpatient treatment with either enoxaparin (40 mg once daily) or a placebo. The primary efficacy end point was the prevalence of objectively confirmed venous thromboembolism or symptomatic pulmonary embolism during the double-blind phase of treatment. RESULTS: Of the 873 randomized patients, 435 underwent elective total hip replacement and 438 underwent elective total knee replacement. Enoxaparin was superior to the placebo in reducing the prevalence of venous thromboembolism in patients treated with hip replacement: 8.0% (eighteen) of the 224 patients treated with enoxaparin had venous thromboembolism compared with 23.2% (forty-nine) of the 211 patients treated with the placebo (p < 0.001; odds ratio, 3.62; 95% confidence interval, 2.00 to 6.55; relative risk reduction, 65.5%). Enoxaparin had no significant benefit in the patients treated with knee replacement: thirty-eight (17.5%) of the 217 patients treated with enoxaparin had venous thromboembolism compared with forty-six (20.8%) of the 221 patients treated with the placebo (p = 0.380; odds ratio, 1.24; 95% confidence interval, 0.76 to 2.02; relative risk reduction, 15.9%). Symptomatic pulmonary embolism developed in three patients, one with a hip replacement and two with a knee replacement; all had received the placebo. There was no significant difference in the prevalence of hemorrhagic episodes or other types of toxicity between the enoxaparin and placebo-treated groups. CONCLUSIONS: Prolonging enoxaparin thromboprophylaxis following hip replacement for a total of four weeks provided therapeutic benefit, by reducing the prevalence of venous thromboembolism, without compromising safety. A similar benefit was not observed in patients treated with knee replacement.

Adult↗
PubMed2001

Prevention of venous thromboembolic disease following primary total knee arthroplasty. A randomized, multicenter, open-label, parallel-group comparison of enoxaparin and warfarin.

BACKGROUND: Patients treated with total knee arthroplasty are at high risk for the development of venous thromboembolism postoperatively. This study compared the efficacy and safety of two common thromboprophylactic agents, enoxaparin (a low-molecular-weight heparin) and warfarin. METHODS: Three hundred and forty-nine patients were included in a prospective, randomized, multicenter, open-label, parallel-group clinical trial. Treatment with enoxaparin (30 mg, administered subcutaneously twice daily) or warfarin (adjusted to an international normalized ratio of 2 to 3) was initiated during the immediate postoperative period, within eight hours after the surgery, and was continued for four to fourteen days. Venous thromboembolism was defined as deep-vein thrombosis documented by contrast venography, symptomatic deep-vein thrombosis documented by lower-extremity ultrasonography, or symptomatic pulmonary embolism confirmed by a positive lung scan or pulmonary angiography. RESULTS: In the all-treated-patients group, eighty (45%) of the 176 warfarin-treated patients had venous thromboembolism: fifty-nine (34%) had distal deep-vein thrombosis; twenty (11%), proximal deep-vein thrombosis; and one (0.6%), pulmonary embolism. Venous thromboembolism developed in significantly fewer (p = 0.0001) enoxaparin-treated patients (forty-four of 173; 25%): forty-one (24%) had distal deep-vein thrombosis, three (2%) had proximal deep-vein thrombosis, and none had pulmonary embolism. The enoxaparin-treated patients also had a significantly lower prevalence of proximal deep-vein thrombosis (p = 0.002). The estimated odds for the development of venous thromboembolism were 2.52 times greater (95% confidence interval, 2.00 to 3.19) with warfarin than they were with enoxaparin. Major hemorrhage occurred in four warfarin-treated patients and nine enoxaparin-treated patients; with the numbers available, this difference was not significant (p = 0.17). Clinically important operative-site hemorrhage occurred in six (3%) of the warfarin-treated patients and twelve (7%) of the enoxaparin-treated patients (p = 0.15). CONCLUSIONS: A fixed 30-mg subcutaneous dose of enoxaparin, administered twice daily, with the first dose administered within eight hours after the completion of surgery, was significantly more effective than adjusted-dose warfarin in reducing the occurrence of asymptomatic venous thromboembolism, including proximal deep-vein thrombosis, in patients undergoing total knee arthroplasty. With the numbers available, there was no significant difference between groups with regard to the occurrence of major hemorrhagic complications; however, the rate of overall hemorrhagic complications was higher in the enoxaparin group.

Adult↗
PubMed2000

Cost for inpatient care of venous thrombosis: a trial of enoxaparin vs standard heparin.

BACKGROUND: Enoxaparin, a low-molecular-weight heparin administered to hospitalized patients once or twice daily, has shown efficacy and safety equivalent to unfractionated heparin in the treatment of acute venous thromboembolic disease. Although the cost of either enoxaparin regimen is greater than that of unfractionated heparin, the overall cost of care for each of these 3 treatment strategies is unknown. METHODS: A cost minimization analysis of a 3-month, partially blinded, randomized, controlled efficacy and safety trial of anticoagulant therapy for deep vein thrombosis. Three hundred thirty-nine hospitalized patients with symptomatic lower extremity deep vein thrombosis were randomly assigned to initial therapy with subcutaneous enoxaparin either once (n = 112) or twice (n = 123) daily, or with dose-adjusted intravenous unfractionated heparin (n = 104), followed by long-term oral anticoagulant therapy. Estimated 1997 total cost from a third-party payer perspective for the 3-month episode of care was calculated by assigning standard unit costs to counts of medical resources used by each patient in the clinical trial. RESULTS: Average total cost for the 3-month episode of care was similar across all 3 treatment regimens: once-daily dose of enoxaparin, $12,166 (95% confidence interval [CI], $10,744-$13,588); twice-daily dose of enoxaparin, $11,558 (95% CI, $10,201-$12,915); and unfractionated heparin, $12,146 (95% CI, $10,670-$12,622). Bootstrapped estimates and sensitivity analyses did not significantly change findings. CONCLUSIONS: There was no significant difference in the overall cost for the 3-month episode of care for patients treated with either enoxaparin or unfractionated heparin. Additional acquisition costs for anticoagulant medication among patients treated with enoxaparin were offset by savings associated with lower incidence of hospital readmission and shorter duration of venous thromboembolism-related readmissions.

Enoxaparin↗
PubMed1997

Enoxaparin, a low-molecular-weight heparin suppresses prothrombin activation more effectively than unfractionated heparin in patients treated for venous thromboembolism.

Although unfractionated heparin (UFH) is standard therapy for venous thromboembolism, there is a clinical failure rate of up to 10%. Newer treatment strategies include low-molecular-weight heparins (LMWH). As part of an international study comparing the efficacy and safety of enoxaparin, a LMWH versus UFH in patients with venous thromboembolism, we studied the effects of enoxaparin and UFH on the plasma concentrations of two activation peptides, fragment 1 + 2 (F1 + 2), and thrombin-antithrombin III (TAT) complexes. We hypothesized that enoxaparin would be more effective in suppressing activation of coagulation. Intravenous heparin was given by bolus injection followed by infusion. There were 2 enoxaparin treatment groups (1 mg/kg s.c., bid and 1.5 mg/kg s.c. daily). Plasma samples were obtained from 11 patients in the enoxaparin group and 6 patients in the heparin group prior to and at 6 hour intervals after initiating therapy. Clinical characteristics of the enoxaparin and UFH patient groups were similar. TAT concentrations were not statistically different between groups at any treatment interval. However, plasma F1 + 2 concentrations differed significantly (p < 0.05); concentrations in the enoxaparin group were consistently lower over time than in the UFH group. These results suggest that this LMWH is more effective in suppressing ongoing thrombosis in vivo than UFH in patients with venous thrombosis.

Adult↗
PubMed1995

Efficacy and safety of enoxaparin versus unfractionated heparin for prevention of deep venous thrombosis after elective knee arthroplasty. Enoxaparin Clinical Trial Group.

This study was a randomized, parallel-group, open-label clinical trial comparing the efficacy and safety of Enoxaparin, a low-molecular-weight heparin, and unfractionated heparin to prevent deep venous thrombosis after elective total knee arthroplasty. Four hundred fifty-three patients were randomized and received study medications. The primary efficacy evaluation was unilateral contrast venography done at the end of study or earlier if clinically indicated. The primary safety outcome was the incidence of bleeding episodes. Patients were assigned to 1 of 2 postoperative treatment groups: Enoxaparin 30 mg subcutaneous every 12 hours (228 patients), or unfractionated heparin 5000 units subcutaneous every 8 hours (225 patients). The incidence of proximal and distal deep venous thrombosis in the Enoxaparin group was 24.6% (56/228), and in the heparin group 34.2% (77/225). Three major hemorrhagic episodes were observed in each treatment group. Two cases of pulmonary embolism occurred in patients receiving heparin (1 fatal); no cases occurred in patients receiving Enoxaparin. This study showed that Enoxaparin administered postoperatively 30 mg every 12 hours is more effective and as safe as unfractionated heparin prophylaxis to prevent deep venous thrombosis in patients having elective total knee arthroplasty.

Aged↗
PubMed1995

Efficacy and safety of enoxaparin to prevent deep vein thrombosis after hip arthroplasty.

Four clinical studies were conducted in the United States and Canada to compare the efficacy and safety of Enoxaparin, a low molecular weight heparin, with low dose unfractionated heparin and placebo for the prevention of deep venous thrombosis after hip arthroplasty. In each study, patients were randomized consecutively into treatment groups of placebo, unfractionated heparin (5000 IU 3 times daily or 7500 IU twice daily), or Enoxaparin (30 mg twice daily, 40 mg once daily, or 10 mg once daily), with treatment started postoperatively. All patients had noninvasive studies and bilateral lower extremity radiocontrast venography at the end of study treatment or on discharge from the hospital (not applicable to the first 24 patients enrolled in the Canada-1 study). One thousand nine hundred forty patients were treated, and 1937 patients were included in efficacy analysis. The incidence of total deep venous thrombosis was as follows: placebo group, 46% (22 of 50 patients); heparin group, 16% (87 of 539 patients); Enoxaparin group, 30 mg twice daily 12% (93 of 785 patients); Enoxaparin 40 mg daily group, 14% (14 of 402 patients); and Enoxaparin 10 mg daily group, 25% (40 of 161 patients). Incidence of proximal deep venous thrombosis was 22%, 5%, 4%, 4%, and 11%, respectively. Major bleeding events were reported in 4% of the placebo group, 2% to 4% in the Enoxaparin group, and 6% in the unfractionated heparin group. In these clinical studies, Enoxaparin, 30 mg twice daily, was shown to be as effective and safe as low dose unfractionated heparin to prevent deep venous thrombosis after hip arthroplasty.

Adult↗
PubMed1994

Efficacy and safety of enoxaparin to prevent deep venous thrombosis after hip replacement surgery. Enoxaparin Clinical Trial Group.

OBJECTIVE: To determine the most effective and safe dose of enoxaparin to prevent deep venous thrombosis in high-risk surgical patients. DESIGN: A double-blind, randomized, multicenter clinical trial. SETTING: Private, university, and government hospitals in the United States. PATIENTS: 572 patients having elective hip replacement surgery, 568 of whom received study medication and had efficacy data available for evaluation. INTERVENTIONS: Patients were randomly assigned to one of three subcutaneous enoxaparin regimens: 10 mg once daily (161 patients); 40 mg once daily (199 patients); and 30 mg every 12 hours (208 patients). Treatment was initiated within 24 hours after surgery and continued for as long as 7 days. Treatment with 10 mg enoxaparin once daily was discontinued prematurely after an interim analysis showed an increased deep venous thrombosis incidence in this treatment group. MEASUREMENTS: Efficacy was determined by bilateral lower extremity venography, noninvasive vascular imaging methods, or clinical evidence on day 7 of treatment or earlier if clinically indicated. RESULTS: Deep venous thrombosis occurred in 25% (40 of 161) of the patients who received 10 mg of enoxaparin once daily; in 14% (27 of 199) of those receiving 40 mg of enoxaparin once daily; and in 11% (22 of 208) in those receiving 30 mg of enoxaparin every 12 hours. The incidence of deep venous thrombosis was significantly higher in patients who received 10 mg of enoxaparin once daily compared with those who received 40 mg of enoxaparin once daily (P = 0.02) or those who received 30 mg of enoxaparin every 12 hours (P < 0.001). The difference between the patients who received 40 mg once daily and those who received 30 mg every 12 hours was not significant. Only two cases of pulmonary embolism were diagnosed, one in patients receiving 40 mg of enoxaparin and one in those receiving 10 mg once daily. The incidence of hemorrhagic complications differed significantly between patients who received 10 mg of enoxaparin once daily (5%, 8 of 161 patients) and those who received 30 mg of enoxaparin every 12 hours (13%, 26 of 208; P < 0.05). CONCLUSIONS: After surgery, enoxaparin, 40 mg once daily or 30 mg every 12 hours, is more effective than a regimen of 10 mg once daily to prevent deep venous thrombosis in patients having elective hip replacement surgery. The regimens of 40 mg once daily and 30 mg every 12 hours provided prophylaxis similar to the most effective drug treatments previously reported. The incidence of hemorrhagic episodes with the regimens of 40 mg once daily and 30 mg twice daily was higher than that observed with 10 mg once daily; however, major hemorrhage occurred in only 4% to 5% of patients receiving the higher-dose regimens. The risk-to-benefit ratio supports the use of enoxaparin as a therapeutic agent to prevent deep venous thrombosis in these patients.

Aged↗
PubMed1994

Low molecular weight heparin in prevention of restenosis after angioplasty. Results of Enoxaparin Restenosis (ERA) Trial.

BACKGROUND: Heparin, an anticoagulant, possesses antiproliferative effects and has been shown to reduce neointimal proliferation and restenosis following vascular injury in experimental studies. METHODS AND RESULTS: The primary aim of this double-blind multicenter study was to determine if 40 mg Enoxaparin, a low molecular weight heparin, administered subcutaneously once daily for 1 month after successful angioplasty would reduce the incidence of restenosis. Four hundred fifty-eight patients were randomized at nine clinical centers (231 to placebo and 227 to Enoxaparin). The primary end point was angiographic or clinical restenosis. Angiographic restenosis was defined as a loss of 50% of the initial gain as measured by quantitative coronary angiography (QCA) at a core laboratory. In the absence of QCA, clinical evidence of restenosis was defined as death, myocardial infarction, repeat revascularization, or worsening angina. Using the intention-to-treat analysis for all patients, restenosis occurred in 51% of the placebo group and 52% of the Enoxaparin group (relative risk, 1.07, P = .625). Likewise, no difference in restenosis was evident when the change in minimal lumen diameter or other angiographic definitions of restenosis were used. Adverse clinical events were infrequent and did not differ between the groups with the exception of minor bleeding complications, which were more common in the Enoxaparin group. CONCLUSIONS: Enoxaparin (40 mg/d SC for 1 month) following successful angioplasty did not reduce the incidence of angiographic restenosis or the occurrence of clinical events over 6 months. The treatment was well tolerated, although in-hospital minor bleeding was more common with active treatment.

Angioplasty, Balloon, Coronary↗
PubMed1994

Use of enoxaparin, a low-molecular-weight heparin, and unfractionated heparin for the prevention of deep venous thrombosis after elective hip replacement. A clinical trial comparing efficacy and safety. Enoxaparin Clinical Trial Group.

A randomized, parallel-group, open-label clinical trial (the physicians, patients, and staff were not blinded with regard to the regimen that had been used) was conducted, between December 1988 and September 1990, to compare the safety and efficacy of enoxaparin, a low-molecular-weight heparin, with the safety and efficacy of unfractionated heparin for the prevention of deep venous thrombosis after elective hip replacement. Six hundred and ten patients were randomized, and 607 patients received one of the study medications. The evaluations of efficacy included contrast-media venography, non-invasive vascular examination, and clinical examination. Data on efficacy were available for 604 patients, who had been assigned to one of three treatment groups: thirty milligrams of enoxaparin every twelve hours (194 patients), forty milligrams of enoxaparin once daily (203 patients), or 5000 units of unfractionated heparin every eight hours (207 patients). All drugs were administered subcutaneously. Dosages were not adjusted on the basis of the results of coagulation tests or the body weight of the patient. Treatment was initiated within twenty-four hours after the operation and continued for a maximum of seven days. The primary safety outcome was the occurrence of bleeding episodes. An intent-to-treat patient analysis revealed that deep venous thrombosis occurred in nine (5 per cent) of the 194 patients who received thirty milligrams of enoxaparin every twelve hours, thirty (15 per cent) of the 203 patients who received forty milligrams of enoxaparin once daily, and twenty-four (12 per cent) of the 207 patients who received unfractionated heparin. The rate of deep venous thrombosis was significantly lower in the group that received thirty milligrams of enoxaparin every twelve hours than in the group that received unfractionated heparin (p = 0.03) and in the group that received forty milligrams of enoxaparin once daily (p = 0.0002). No clinically symptomatic pulmonary embolism was observed during the treatment or follow-up phase of this study in the group that received thirty milligrams of enoxaparin every twelve hours. Analysis of evaluable patients revealed a marked reduction in the rate of deep venous thrombosis in the group that received thirty milligrams of enoxaparin every twelve hours (eight [6 per cent] of 136 patients) compared with the group that received heparin (twenty-one [15 per cent] of 145 patients) (p = 0.10); however, this difference was not significant because of the small number of patients included in this analysis.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMed1994

Incidence of posthospitalization proximal deep venous thrombosis after total hip arthroplasty. A pilot study.

The incidence of venous thromboembolic disease after hospitalization for elective total hip arthroplasty (THA) was evaluated in a prospective pilot study of 42 patients. Before discharge from the hospital, all patients were free of deep venous thrombosis (DVT) (bilateral lower extremity ascending venography, 38 patients; duplex ultrasonography, two patients; or a combination of both, two patients). After discharge from the hospital, each patient had bilateral duplex ultrasonography and clinical evaluation monthly for three months. Venography was performed when the noninvasive test suggested the presence of DVT. Four (10.5%) of 38 completed patients (95% confidence interval, 4.4-24.8%) developed proximal DVT after hospitalization. Two episodes occurred during the first month after discharge and two during the second month. Three of the four episodes involved the surgically treated extremity. This pilot experience suggests that a significant risk of DVT continues for at least two months after THA. This observation adds support for the emerging clinical trend to continue DVT prophylaxis for at least two months after hospitalization. Further study regarding the incidence of late DVT and its effective prophylaxis seems warranted.

Adult↗
PubMed1993

Enoxaparin: the low-molecular-weight heparin for prevention of postoperative thromboembolic complications.

OBJECTIVE: To introduce readers to a new low-molecular-weight heparin (LMWH) product, enoxaparin. The chemistry, pharmacology, pharmacodynamics, clinical efficacy in thromboembolic prophylaxis following surgery, and adverse effects are reviewed. DATA SOURCES: A MEDLINE search of the English-language literature was used to identify relevant literature. STUDY SELECTION: A focus was placed on human clinical studies with well-accepted measures of antithrombotic efficacy endpoints, i.e., venography and ultrasonography. Emphasis was on pharmacologic and pharmacokinetic studies conducted in humans. DATA EXTRACTION: Most data were extracted from double-blind, controlled clinical studies. Other study designs were accepted if the results were believed to be significant. Pharmacology and pharmacokinetic data were selected from studies with exceptional design conducted in humans. DATA SYNTHESIS: Enoxaparin is a polysaccharide chain produced by the depolymerization of heparin. In comparison with heparin, which has an average molecular weight of 12,000-15,000 daltons, the average molecular weight of enoxaparin is approximately 4500 daltons. Enoxaparin does not form a complex with antithrombin III and thrombin as extensively as does heparin; however, the anti-Xa activity of enoxaparin is similar. The significance of this fact is an enhancement of antithrombotic activity and clinical efficacy. Trials comparing enoxaparin with other thromboembolic prophylaxis techniques are ongoing. CONCLUSIONS: Thromboembolism remains one of the major complications of all surgical procedures. Attempts have been made throughout the last century to develop the most effective means to prevent this complication. Clinical studies performed throughout the world have shown that enoxaparin is superior or equivalent to other antithrombotic agents, including heparin, in preventing the formation of venous thromboembolism. In addition, enoxaparin appears to possess an equivalent or lower incidence of bleeding complications when compared with heparin prophylaxis. Enoxaparin is expected to be joined by other LMWH products in the future. As a result, the methods of providing effective prophylaxis against thromboembolic complications is expected to change in the coming years.

Clinical Trials as Topic↗
PubMed1986

Pharmacokinetics of intravenous clindamycin in newborn infants.

We studied 12 newborn infants (gestational ages 26-39 wk [mean +/- SD, 30.6 +/- 4.7]; birth weight 640-2700 g, [mean, 1,322 +/- 688]; postnatal age 1-24 days [mean, 9.6 +/- 8.5]) who received clindamycin phosphate for suspected or proven necrotizing enterocolitis (ten patients) or suspected anaerobic septicemia (two patients) in doses of 3.2-11 mg/kg every six hours. Range of mean serum concentration of clindamycin at steady state was between 12.7 and 40 micrograms/ml (therapeutic range = 2-10 micrograms/ml). High concentrations could be attributed to elimination T1/2 (6.3 +/- 2.1 hr) 100% longer than in older children or adults. Clindamycin clearance (61.6 +/- 31.6 hr ml/kg/hr) was lower than in older children or adults. Because of the observed prolongation in T1/2 and correspondingly lower clearance, the IV dose of clindamycin in newborn infants should be reduced to 15-20 mg/kg/day given in four daily doses.

Clindamycin↗
PubMed1981

Sensitivity of myeloid progenitor cells in healthy subjects and patients with chronic myeloid leukemia to chemotherapeutic agents.

The different sensitivity of myeloid progenitor cells (CFUc) to chemotherapeutic agents was measured with an in vitro clonogenic assay. Normal marrow and peripheral blood CFUc and blood CFUc obtained from patients with chronic myelogenous leukemia (CML) were tested for their sensitivity to medications used currently in the management of CML. The drugs tested were adriamycin, L-asparaginase, busulfan, beta-cytosine arabinoside (Ara-C), daunorubicin, hydroxyurea, melphalan, and thioguanine. CML CFUc were significantly more sensitive to Ara-C [drug dose required for 90% inhibition of CFUc growth (LD90) = 0.015 +/- 0.003 microgram/ml] than were normal CFUc (LD90 = 0.038 +/- 0.009 microgram/ml). A shift to enhanced sensitivity to L-asparaginase was detected in patients studied sequentially who entered blast transformation during this study. In vitro and in vivo pharmacokinetic data are compared.

Antineoplastic Agents↗
PubMed1981

Chemotherapeutic sensitivity of normal and leukemic hematopoietic progenitor cells to N-[4-(9-acridinylamino)-3-methoxyphenyl]-methanesulfonamide, a new anticancer agent.

The sensitivities of hematopoietic colony-forming cells (CFC) to N-[4-(9-acridinylamino)-3-methoxyphenyl]-methanesulfonamide (NSC-249992) (m-AMSA) were measured with an in vitro clonogenic assay, a modification of the Robinson and Pike human marrow culture system. CFC derived from bone marrow and peripheral blood of normal subjects and patients with chronic myeloid leukemia (CML) were studied. Sensitivities to m-AMSA did not differ significantly between normal marrow and blood CFC, between normal and CML CFC, or between CML CFC obtained from patients with leukemias in chronic phase and blast transformation. Drug doses and exposure times producing in vitro hematopoietic inhibition were comparable to clinically employed drug dosages and schedules associated with hematopoietic toxicity.

Aminoacridines↗