Dalteparin for prevention of catheter-related complications in cancer patients with central venous catheters: final results of a double-blind, placebo-controlled phase III trial.

BACKGROUND: Cancer patients receiving chemotherapy experience thromboembolic complications associated with the use of long-term indwelling central venous catheters (CVCs). This prospective, double-blind, placebo-controlled, multicenter study evaluated whether prophylactic treatment with a low molecular weight heparin could prevent clinically relevant catheter-related thrombosis. PATIENTS AND METHODS: Patients with cancer undergoing chemotherapy for at least 12 weeks (n=439) were randomly assigned, in a 2:1 ratio, to receive either dalteparin (5000 IU) or placebo, by subcutaneous injection, once daily for 16 weeks. Patients underwent upper extremity evaluation with either venography or ultrasound at the time of a suspected catheter-related complication (CRC) or upon completion of study medication. The primary end point, as determined by a blinded adjudication committee, was the occurrence of a CRC, defined as the first occurrence of any one of the following: clinically relevant catheter-related thrombosis that was symptomatic or that required anticoagulant or fibrinolytic therapy; catheter-related clinically relevant pulmonary embolism; or catheter obstruction requiring catheter removal. RESULTS: There was no significant difference in the frequency of CRCs between the dalteparin arm (3.7%) and the placebo arm (3.4%; P=0.88), corresponding to a relative risk of 1.0883 (95% confidence interval 0.37-3.19). No difference in the time to CRC was observed between the two arms (P=0.83). There was no significant difference between the dalteparin and placebo groups in terms of major bleeding (1 versus 0) or overall safety. CONCLUSIONS: Dalteparin prophylaxis did not reduce the frequency of thromboembolic complications after CVC implantation in cancer patients. Dalteparin was demonstrated to be safe over 16 weeks of treatment in these patients.

Accuracy of endoscopic ultrasonography in upper gastrointestinal submucosal lesions: a prospective multicenter study.

BACKGROUND: Endoscopic ultrasonography (EUS) is commonly agreed to be the best imaging method for diagnosing and differentiating between submucosal lesions in the gastrointestinal tract. However, most of the current evidence for this derives from retrospective multicenter studies. A prospective multicenter analysis of the performance of EUS in diagnosing submucosal lesions in everyday practice was therefore conducted. METHODS: Over a 2-year period, this study included 150 patients (52% men, mean age 59.8 years) from 23 centers who had a presumptive diagnosis of a submucosal lesion on upper gastrointestinal endoscopy. The patients' symptoms and EUS results were recorded. Endoscopic and endosonographic findings regarding lesion size, layer of origin, and the presumptive diagnosis (benign or malignant) were recorded. The reference methods used were surgery, biopsy, other imaging tests, and a follow-up period of 6 months. RESULTS: Of the 150 patients, 102 had an intramural lesion (84 tumors, 18 other lesions such as cysts, aberrant pancreas, etc.), and 48 had an extraluminal compression--in most cases (n = 35) by normal organs or structures. For differentiating between a submucosal and an extraluminal compression, the sensitivity and specificity of endoscopy were 87% and 29%, whereas those of EUS were 92% and 100%. However, the sensitivity and specificity of EUS for differentiating between malignant and benign submucosal tumors were only 64% and 80%, respectively. CONCLUSIONS: The accuracy of EUS in differentiating between submucosal tumors and extraluminal compressions is substantially superior to that of endoscopy, but EUS is still inadequate for differential diagnosis between benign and malignant submucosal tumors. However, EUS is still the best method of visualizing submucosal lesions precisely. The influence of EUS on the further management in these patients remains to be examined in subsequent studies.

Phase II study of weekly paclitaxel plus 24-h continuous infusion 5-fluorouracil, folinic acid and 3-weekly cisplatin for the treatment of patients with advanced gastric cancer.

The aim of this study was to evaluate the toxicity and efficacy of combination chemotherapy with weekly 24-h continuous infusion of 5-fluorouracil (5-FU)/folinic acid, weekly paclitaxel and 3-weekly cisplatin in patients with unresectable, locally advanced or metastatic gastric adenocarcinoma. Between November 1999 and November 2001, 29 chemotherapy-naive patients (13 male and 16 female) with a median age of 56 years (range 22-72) were consecutively enrolled at three centers. 5-FU 2 g/m2 was given weekly over 24 h i.v. preceded by folinic acid 500 mg/m2 as a 2-h infusion. Paclitaxel 80 mg/m2 was administered as a 1-h infusion weekly and cisplatin 50 mg/m2 as 1-h infusion on days 8 and 29. Six weeks of therapy (days 1, 8, 15, 22, 29 and 36) followed by 1 week of rest was considered one cycle. A median of 3 cycles (range 1-5) was administered to 29 patients with a total of 73 cycles applied. All patients were assessable for toxicity and survival, 28 patients were assessable for response (one patient received less than one complete cycle and could not be evaluated for response). Four patients (14%) obtained a complete response and 10 patients (34%) a partial response (overall response rate 48%, 95% CI 29-68%). Seven patients (24%) had stable disease. Seven patients (24%) had progressive disease during or within 4 weeks after treatment. The median progression-free and overall survival times were 8 months (range 1-23) and 11 months (range 1-23), respectively. Overall toxicity was acceptable. Hematological toxicity was favorable with only one patient (3%) experiencing WHO grade 3/4 leukocytopenia and one patient (3%) WHO grade 3/4 anemia. Non-hematologic WHO grade 3/4 toxicities included alopecia in 19 (66%), nausea/vomiting in six (21%), diarrhea in six (21%), neurotoxicity grade 3 in three (10%) and infection in three (10%) patients. A total of 42 applications (10%) (range 0-5) had to be postponed and dose reductions of at least one drug was necessary in 37% of applications. In three patients (10%) treatment was stopped because of toxicity. All patients were treated on an outpatient basis. Thus, the combination of weekly paclitaxel, cisplatin and continuously infused 5-FU/folinic acid appears to be a highly active regimen for the treatment of patients with advanced gastric cancer. Compared with our previous experience with the same combination of drugs but using paclitaxel at 175 mg/m2 given every 3 weeks, the protocol with weekly application of paclitaxel 80 mg/m2 shows a reduced incidence of hematologic toxicity, particularly leukopenia. Other organ toxicities apart from a slightly higher incidence of peripheral neuropathy were comparable between the two treatment protocols. Efficacy with a response rate of 50% was well preserved by this weekly regimen.

A phase II study of paclitaxel, weekly, 24-hour continous infusion 5-fluorouracil, folinic acid and cisplatin in patients with advanced gastric cancer.

To evaluate the toxicity and efficacy of combination chemotherapy with paclitaxel, cisplatin and 24 h continuous infusion of 5-FU/folinic acid in patients (pts) with unresectable, locally advanced or metastatic gastric adenocarcinoma. Forty-five chemotherapy-naive pts (28 male and 17 female) with a median age of 60 years (range 35-74) were enrolled. 5-FU 2 g/m2 was given weekly over 24 h i.v. preceded by folinic acid 500 mg/m2 as a 2 h infusion. Paclitaxel 175 mg/m2 was administered as a 3 h-infusion on days 1 and 22 and cisplatin 50 mg/m2 as 1 h infusion on days 8 and 29. Six weeks of therapy (days 1, 8, 15, 22, 29, 36) followed by 2 weeks rest were considered one cycle. A median of 3 cycles (range 1-4) were administered to 45 pts assessable for response, survival and toxicity. Five pts (11%) obtained a CR and 18 pts (40%) a PR (ORR 51%; 95% CI: 35.8-66.3%). Responses were achieved in the liver, lymph nodes, lungs and at the site of the primary tumour. Nine pts (20%) had stable disease. Thirteen pts (29%) were considered to have failed treatment, 8 pts (18%) due to progressive disease and 5 pts (11%) who did not receive one complete cycle of therapy due to acute non-haematologic toxicity. The median progression-free and overall survival times were 9 months (range 1-36+) and 14 months (range 2-36+), respectively. Neutropenia WHO III(o)/IV(o) occurred in 7 pts (15%) with only 1 pt having grade IV. Additional non-haematologic WHO III(o)/IV(o) toxicities included nausea/vomiting in 5 (11%), alopecia in 22 (49%), and diarrhoea in 1 patient each (2%). Dose reductions or treatment delays were necessary in 8 pts (17%), mainly due to neutropenia. All pts were treated on an outpatient basis. The combination of paclitaxel, cisplatin and continuously infused 5-FU/folinic acid appears to be a highly active regimen for the treatment of pts with advanced gastric cancer. While the overall acceptable toxicity allows its use in the palliative setting, it may also be an attractive option to be tested for neoadjuvant or adjuvant treatment.

[Variation in nocturnal blood pressure behavior in stage III (WHO) hypertension--a case report]. / Abweichungen des nächtlichen Blutdruckverhaltens bei Hypertonie vom Schweregrad III (WHO)-eine kasuistische Betrachtung.

In some cases of hypertensive men the authors obtained 24-hour blood pressure profiles by easy non-invasive technique (Mercury manometer) and under the usual atmosphere and activities of a hospital. The control Group, 32 normotensive men, showed a normal circadian blood pressure variability with systolic acrophases at 10.00 h and 16.00 h and a bathyphase around 3.00 h. The diastolic blood pressure had a smaller variability. One patient with essential hypertension stage II (WHO), case 1, kept the normal day-night rhythm. By case 2, a man with essential hypertension stage III (WHO), the authors refer to the possibility of considerable differences of blood pressure behaviour during the night in cases of severe hypertension in contrary to normal blood pressure variability. After a supplementary fourth medication this patient showed a significant decrease of blood pressure during the night. Nevertheless he kept his acrophase at night. The recording of day-night profiles of blood pressure seems to be useful in relation to the judgement of classification of severity, of the mode of anti-hypertensive medication and of the success in therapy.