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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.

Twenty patients received 28 courses of 5FUDR (floxuridine) admixed with Cisplatin (CDDP) and administered as a continuous infusion for 24 hours for 14 consecutive days. Pharmaceutical studies of the admixture of 5FU with CDDP and 5FUDR with CDDP demonstrated that only 5FUDR was compatible with CDDP and that the admixture was stable for 7 days. This Phase I study established the optimal dose rate for the individual components of the admixture and demonstrated that CDDP decreases the maximum tolerated dose rate for 5FUDR. The optimal dose rate for 5FUDR is 0.075 mg/Kg/d, and for CDDP the optimal dose rate is 7.5 mg/M2/d. Dose rate limiting toxicity is an enteritis which is radiographically similar to regional enteritis and is related to the 5FUDR. An ancillary finding was a significant decrease in serum magnesium levels in 11 of 13 monitored courses presumably related to the platinum.

Two consecutive Phase I trials of continuous infusion 5-fluorouracil (5-FU) or floxuridine (5-FUdR) admixed with leucovorin (LCV) were performed and involved 19 and 24 patients, respectively. The studies were carried out to identify the optimal dose rate of delivery for the two admixtures (5-FU + LCV and 5-FUdR + LCV) administered for 14 days, and to determine if biochemical modulation could be identified. The optimal dose rates for 5-FU plus LCV were 200 mg/m2/d and 5 mg/m2/d, respectively. The optimal dose rates for 5-FUdR plus LCV were 0.075 mg/kg/d and 5 mg/m2/d, respectively. The dose rate limiting toxicity for 5-FU plus LCV was stomatitis and for 5-FUdR plus LCV it was diarrhea. LCV administered as an admixture with either 5-FU or 5-FUdR on an infusion schedule decreases the optimally tolerated dose rates for these two agents to 83% and 60%, respectively. This is achieved with low-dose LCV infusions.

The presence of cold-reactive proteins may pose special hazards to the patient about to undergo hypothermic cardiopulmonary bypass, topical myocardial cooling, and cold potassium cardioplegic arrest. The detection and characterization of such proteins, their potential adverse effects, and a proposed management protocol are discussed.

5-Fluorouracil (5-FU) and floxuridine (FUdR) were admixed in a single solution and administered via a central venous catheter on a continuous infusion schedule for 14 days. The Phase I trial design developed for admixture combinations was employed with starting doses for 5-FU at 250 mg/m2/day and for FUdR at 0.075 mg/kg/day. Twenty patients and 28 courses were studied. Dose rate limiting toxicity was pseudoregional enteritis with or without stomatitis experienced by five of ten of the courses administered at the highest dose rates of the admixture components. The simultaneous delivery of the two agents results in a modest compromise of the cumulative dose delivered for FUdR. Previous Phase I studies of single agent 5-FU and FUdR had demonstrated that the optimal dose rates for the individual agents in a 14-day continuous 24-hour infusion schedule is 350 mg/m2/d and 0.125 mg/Kg/day, respectively. The maximum dose rate of 5-FU at 350 mg/m2/day for 14 days is not restricted even with the addition of FUdR at up to 0.1 mg/kg/day. The optimal dose rates for Phase II trails should be as follows: 5-FU, 350 mg/m2/day; and FUdR, 0.1 mg/kg/day.

To evaluate the usefulness of plasma calcitonin as an index of tumor burden and disease activity, we undertook a prospective study of serial calcitonin measurements in a group of patients with small cell carcinoma of the lung from diagnosis throughout a period of intensive therapy. Plasma calcitonin was significantly elevated in 84% of patients with extensive small cell carcinoma of the lung and was not elevated in patients with limited disease at the time of diagnosis. The elevated values fell significantly in response to chemotherapy and radiation therapy, and reflected regression of followable disease and improvement in clinical status. A significant correlation existed between plasma calcitonin and extent of disease. Relapse was generally associated with an increase in elevated plasma calcitonin levels, and calcitonin appeared to reflect tumor burden. The serial measurement of plasma calcitonin is useful in the management of the patient with small cell carcinoma of the lung.

PLATELETS have long been implicated as a cause of acute myocardial ischemia,1 2 3 but absolute proof is lacking. Attempts to quantitate in vivo platelet activation during myocardial ischemia have led to the development of a number of indexes of platelet involvement, including the measurement of platelet aggregates4 and of platelet-specific proteins such as β-thromboglobulin and platelet factor 4. However, results have been inconsistent5 , 6 and controversial, and platelets may not be involved in acute myocardial ischemia. Recently, Green and his coworkers presented evidence that patients with coronary-artery disease who are undergoing exercise-stress testing have elevations in platelet factor 4,7 a heparin-neutralizing protein . . .