Potential use of a low-molecular-weight heparin to prevent restenosis in patients with extensive wall damage following peripheral angioplasty.

The long-term outcome of primary successful percutaneous transluminal angioplasty (PTA) for patients with peripheral occlusive arterial disease (POAD) is frequently compromised by the development of restenosis, especially when extensive dissections result from the angioplastic procedure. Unfortunately, prevention of the occlusive process by means of drugs such as antithrombotics, anticoagulants, thrombolytics, corticosteroids, lipid reducers, or cytostatics has not been demonstrated convincingly. The authors sought to clarify whether such patients could benefit from the postsurgical administration of low-molecular-weight heparin. A total of 172 POAD patients with extensive dissections after PTA in the pelvic or upper leg regions were randomized for 7-day post-PTA intravenous treatment with either full heparinization or nadroparin calcium followed by adjunctive oral aspirin for 6 months. The primary outcome measure was the degree of stenosis (normal findings; stenosis < 50%, > 50%, > 80%, occlusion) before and after angioplasty, as well as 3 weeks and 3 and 6 months after dilation; secondary efficacy criteria included changes in the Fontaine stage and in the crurobrachial ratio. No significant treatment-related differences were found at the 3 post-PTA follow-up examinations with regard to the degree of stenosis. This was also the case for the subgroup of patients (n = 62) who had undergone angioplasty in the pelvic region. By contrast, when angioplasty was performed in the superficial femoral artery (n = 110), the degree of restenosis was significantly lower (p<0.01) among patients receiving nadroparin calcium compared to those given heparin at week 3, month 3, and month 6. No intergroup differences emerged for secondary outcome measures in the long term or for safety parameters. These preliminary results indicate that patients with extensive dissections after PTA treatment for POAD in the upper leg region might benefit from a reduction in the rate of restenosis by administration of 7-day weight-adjusted nadroparin calcium.

Short- and long-term results of abciximab versus aspirin in conjunction with thrombolysis for patients with peripheral occlusive arterial disease and arterial thrombosis.

Acute peripheral occlusive arterial disease is an important cause of morbidity and mortality, particularly among older persons. Catheter-directed thrombolytic therapy is the treatment of choice but has limitations: long lytic times, occlusions refractory to thrombolysis, and a high rate of restenosis. We conducted a pilot study to evaluate the use of the platelet GP IIb/IIIa receptor antagonist abciximab versus aspirin in conjunction with thrombolysis in patients with acute peripheral occlusive arterial disease associated with arterial thrombosis. A total of 84 patients were randomized into two equal groups to receive 5 mg recombinant tissue plasminogen activator intravenously and 500 IU heparin/hour along with either 500 mg acetylsalicylic acid or a bolus of 0.25 mg/kg abciximab followed by 10 microg/min abciximab over 12 hours (heparin reduced to 250 IU/hour). Primary efficacy criteria included the number of rehospitalizations, reinterventions, and amputations during the following 6 months. Secondary endpoints were the changes in the Fontaine stage, Bollinger index (vessel occlusion), ankle-to-brachial ratios, distance to claudication after 6 months, and the duration of the initial local lysis treatment. Adjunctive use of abciximab reduced the rates of rehospitalization, reinterventions, and amputations versus results with the use of aspirin (10 vs 14 occurrences, respectively; 9 vs 11; 3 vs 5; when summed, intergroup difference p < 0.05). Secondary peripheral occlusive arterial disease variables became highly significant versus aspirin (p < 0.001 or greater) at 3 and 6 months after treatment. The duration of lysis was markedly shorter upon addition of abciximab versus aspirin (75 vs 110 min; p < 0.001). No major bleeding complications or embolisms occurred. These preliminary results indicate that abciximab may have a useful role when used adjunctively with a thrombolytic agent in older persons with acute peripheral occlusive arterial disease and arterial thrombosis.

Short- and long-term results after thrombolytic treatment of deep venous thrombosis.

OBJECTIVES: The goal of this study was to assess the short- and long-term efficacy of different thrombolytic therapy regimens in patients with leg or pelvic deep venous thrombosis (DVT). BACKGROUND: It is unclear whether locoregional or systemic thrombolysis is superior in treating acute leg DVT or even whether lysis is more effective than anticoagulation therapy in preventing postthrombotic syndrome. METHODS: A total of 250 patients averaging 40 years of age with acute DVT were randomized into five groups to receive full heparinization (1,000 IU/h) and compression treatment, with four groups also administered locoregional tissue plasminogen activator (20 mg/day) or urokinase (100,000 IU/day) or systemic streptokinase (3,000,000 IU daily) or urokinase (5,000,000 IU daily). All groups then received anticoagulation and compression treatment for one year. Primary efficacy criteria included the change after one year in the number of closed vein segments and the occurrence of postthrombotic syndrome. RESULTS: Systemic thrombolytic therapy significantly reduced the number of closed vein segments after 12 months in patients with acute DVT compared with conventional treatment (p < 0.05). Postthrombotic syndrome also occurred with less frequency in systemically treated patients versus controls (p < 0.001). High-dose thrombolysis led to better rates of complete recanalization after seven days (p < 0.01) than locoregional lysis. However, 12 patients receiving thrombolysis (9 systemic, 3 local) suffered major bleeding complications; 9 patients on systemic treatment developed pulmonary emboli. CONCLUSIONS: Systemic thrombolytic treatment for acute DVT achieved a significantly better short- and long-term clinical outcome than conventional heparin/anticoagulation therapy but at the expense of a serious increase in major bleeding and pulmonary emboli. Given the inherent risks for such serious complications, systemic thrombolysis, although effective, should be used selectively in limb-threatening thrombotic situations.

Comparative results of thrombolysis treatment with rt-PA and urokinase: a pilot study.

BACKGROUND: The aim of the following prospective study was to investigate whether patients benefited from locoregional lysis treatment of recent deep leg vein thrombosis after 1 year. PATIENTS AND METHODS: The prospective study included 69 patients aged between 22 and 58 years, in whom recent lower leg vein and popliteal vein thromboses were diagnosed by phlebography. Patients were randomized to one of three treatment groups: one group was treated for a maximum of 7 days with full heparinization and daily dose of 20 mg rt-PA administered locoregionally over a period of 4 hours; a second group received 100,000 IU/h urokinase locoregionally for a maximum of 7 days, in addition to full heparinization; and in the third group (control group), intravenous heparin infusions after PTT constituted the only form of treatment. All patients were given phenprocoumon from day 7 and received compression treatment. Before treatment began and before the course of phenprocoumon started, phlebography and colour duplex sonography examinations were carried out. After 12 months, follow-up duplex sonography was conducted to evaluate the reflux times over the popliteal vein and the degree of patency of the deep leg veins. RESULTS: Complete lysis was achieved in 6 of 22 patients in the recombinant tissue plasminogen activator (rt-PA) group and in 11 of 22 patients in the urokinase group. At follow-up examination after 12 months, there were serious post-thrombotic changes in 14 of 22 patients in the rt-PA group, in 9 of 22 patients in the urokinase group and in 15 of 22 patients in the group of patients who received no lysis treatment. CONCLUSION: Patients with recently formed thromboses in the lower leg and popliteal veins who underwent 7 days of locoregional lysis treatment with urokinase demonstrated significantly fewer clinical symptoms of post-thrombotic syndrome after 1 year than those who received locoregional treatment with rt-PA over a similar period or a control group treated with anticoagulants only.

A phase II trial of paclitaxel and weekly 24 h infusion of 5-fluorouracil/folinic acid in patients with advanced gastric cancer.

A phase II trial was performed to evaluate the efficacy and toxicity of the combination of paclitaxel and 5-fluorouracil (5-FU)/folinic acid in patients with advanced gastric carcinoma. Twenty-two patients (six female and 16 male) with advanced or metastatic disease were enrolled. None of them had received prior chemotherapy. Paclitaxel was administrated as a 3 h infusion of 175 mg/m2 at days 1 and 22, 5-FU 2000 mg/m2 i.v. over 24 h and folinic acid 500 mg/m2 i.v. 2 h prior to 5-FU weekly from days 1 to 36. Seven patients (32%) had partial remissions including the lungs, skin, lymph nodes and locally advanced primary tumor. The median overall survival was 11 months (range 1-17+) and the median progression-free interval was 8 months (range 1-13+). Neutropenia (WHO grade III/IV) occurred in 14% of patients. Other main toxicities were alopecia in 45%, fever/infection in 9%, and nausea/vomiting and diarrhea in 5%. In conclusion, the combination of paclitaxel and continuously infused 5-FU/folinic acid appears to be an active regimen for advanced gastric carcinoma with a remission rate comparable to ELF or FAMtx. The moderate toxicity allows treatment on an outpatient basis.

Paclitaxel and weekly 24-hour infusion of 5-fluorouracil/folinic acid in advanced gastric cancer.

The current phase II study evaluates the safety and efficacy of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and 5-fluorouracil (5-FU) plus folinic acid in patients with advanced gastric cancer. Paclitaxel 175 mg/m2 was given intravenously over 3 hours on days 1 and 22; folinic acid 500 mg/m2 given intravenously over 2 hours followed by 5-FU 2,000 mg/m2 given intravenously over 24 hours was administered on days 1, 8, 15, 22, 29, and 36. Six weeks of treatment were considered one cycle, and each cycle was followed by 2 weeks off treatment. Twenty-two patients (six women and 16 men) with advanced/metastatic gastric cancer were entered on trial. All patients are evaluable for response and toxicity. None had received prior chemotherapy. Radiologically metastatic sites included gastric lymph nodes (64%), liver (36%), lungs (18%), peritoneum (18%), bone (9%), and skin (5%). No complete responses were observed. Seven patients (32%; 95% confidence interval, 12% to 52%) had a partial response. Sites of partial responses included the lungs, skin, lymph nodes, and locally advanced tumor. Twelve patients (55%) had stable disease and three (14%) had disease progression. At a median follow-up of 12 months (range, 1 to 17+ months), the median overall survival for all patients was 11 months (range, 1 to 17+ months; 95% confidence interval, 6.8 to 18.2) and the median progression-free interval was 8 months (range, 1 to 13+ months; 95% confidence interval, 4.7 to 9.8). Severe nonhematologic toxicities were alopecia (45%), fever/infection (9%), diarrhea (5%), and nausea/vomiting (5%). Grade 3/4 neutropenia occurred in three patients (14%). In summary, paclitaxel given every 3 weeks in combination with once-weekly, 24-hour continuous infusions of 5-FU/folinic acid is active in advanced gastric cancer and appears to achieve response rates comparable to regimens like etoposide/folinic acid/5-FU or 5-FU/doxorubicin/methotrexate. The toxicity of this new combination is moderate and allows treatment in an outpatient setting. Ongoing studies are evaluating the activity of paclitaxel combined with weekly continuous infusions of 5-FU/folinic acid with or without cisplatin.