A phase II study of gemcitabine in patients with relapsed or refractory low-grade non-Hodgkin lymphoma.

PURPOSE: The purpose of this study was to determine the tolerability, clinical response rate, and time to disease progression of gemcitabine treatment in patients with low-grade non-Hodgkin lymphoma. (NHL) PATIENTS AND METHODS: Twenty patients with low-grade NHL and progression of disease after at least 1 prior treatment regimen were prospectively enrolled. The treatment regimen consisted of 1200 mg/m2 gemcitabine intravenously administered weekly for 7 weeks followed by a 1-week rest. Subsequent treatment was given weekly for 3 weeks followed by a 1-week rest and repeated for a maximal treatment of 6 cycles until disease progression or unacceptable toxicity. RESULTS: The predominant histologic subtypes among our patients were small lymphocytic (8 of 20) and follicular (7 of 20). Grade III/IV hematologic toxicity was observed in 15 of 20 patients and dose reductions or treatment delays occurred in 19 of 20 patients. Fatigue and asthenia were treatment-limiting in many patients. There were no complete or partial responses observed and only 2 patients had stable disease after 12 weeks of treatment. The average time to progression or off-study status was 2.3 months (95% confidence interval, 1.7-2.9) with 8 patients showing progression of disease. Twelve patients were taken off the study as a result of unacceptable toxicity before observed progression of disease. No patient completed the planned course of therapy. With a median follow up of 10.2 months, 10 of 20 patients remained alive. CONCLUSION: Gemcitabine as a single agent, in this dosage and schedule, has minimal clinical activity in relapsed or refractory low-grade lymphomas and was associated with considerable toxicity. Therefore, further study of gemcitabine in this setting is not justified.

A feasibility study of continuing dose-reduced warfarin for invasive procedures in patients with high thromboembolic risk.

BACKGROUND: The management of perioperative anticoagulation therapy for patients having a high risk of thromboembolism who are receiving long-term oral anticoagulant therapy is uncertain. The prevalent approach is to discontinue oral anticoagulation therapy and initiate heparin therapy. Another potential strategy is to continue oral anticoagulation therapy with a temporary adjustment of warfarin intensity to a preoperative international normalized ratio (INR) of 1.5 to 2.0. Such moderate-dose anticoagulation therapy with warfarin has been shown to be hemostatically safe yet effective in the prevention of thromboembolism after hip or knee replacement. METHODS: Over an 11-year period (ie, 1993 to 2003), our hemostatic consultative service prospectively identified 100 consecutive patients for whom we continued warfarin therapy at adjusted doses during the perioperative period, targeting a goal for the INR of 1.5 to 2.0. Patients were assigned a score for venous thromboembolic risk as well as overall surgical risk using published instruments. Score assignment was based on what was deemed to be extremely high risk for thromboembolism in patients who were receiving long-term warfarin therapy. Although the patients were accrued prospectively, the final retrospective analysis was made after all patients were treated. RESULTS: The most common indication (62%) for high-risk assignment was a thromboembolic event within the past 6 months. The second most prevalent reason was prior postoperative venous thromboembolism (VTE) [11%]. Indications for long-term anticoagulation therapy were recent VTE (62%), inherited thrombophilia (7%), antiphospholipid syndrome (13%), mechanical heart valves (18%), and prior cerebrovascular accident (4%). The prevalence of inherited thrombophilia probably has been grossly underestimated, as neither factor V Leiden mutation nor prothrombin 20210 mutation had been described during the bulk of the accrual time. Most surgical procedures (58%) were significantly invasive (Johns Hopkins category 3 to 5). The mean INR values were 2.1 on the day prior to surgery (SD, 0.9594; range, 1.2 to 6.5; n = 65), 1.8 on the day of surgery (SD, 0.4899; range, 1.2 to 4.9; n = 75), and 1.8 on the first postoperative day (SD, 0.4436; range, 1.1 to 3.3; n = 70). Two patients had major bleeding, and four patients had minor bleeding. One patient developed deep venous thrombosis. Several weeks after surgery, one patient with a prosthetic heart valve died from an embolic stroke, which was associated with a failure to increase his anticoagulation to therapeutic levels. CONCLUSIONS: Moderate-intensity anticoagulant therapy with warfarin, targeting a goal INR of 1.5 to 2.0, appears to be a safe and feasible method for preventing thromboembolic complications in high-risk surgical patients who are receiving long-term oral anticoagulant therapy. This may be considered a reasonable method to afford thromboprophylaxis in highly selected patients who are occasionally seen in clinical practice. This observational study does not prove equality, let alone superiority, to other proposed methods of anticoagulation therapy.