Phase I study of fludarabine plus cyclophosphamide in patients with previously untreated low-grade lymphoma: results and and long-term follow-up--a report from the Eastern Cooperative Oncology Group.

PURPOSE: To determine the toxicity and recommended phase II doses of the combination of fludarabine plus cyclophosphamide in chemotherapy-naive patients with low-grade lymphoma. PATIENTS AND METHODS: Previously untreated patients with low-grade lymphoma were entered onto dosing cohorts of four patients each. The cyclophosphamide dose, given on day 1, was increased from 600 to 1, 000 mg/m(2). Fludarabine 20 mg/m(2) was administered on days 1 through 5. The first eight patients were treated every 21 days; later patients were treated every 28 days. Prophylactic antibiotics were required. RESULTS: Prolonged cytopenia and pulmonary toxicity each occurred in three of eight patients treated every 3 weeks. The 19 patients treated every 28 days, who were given granulocyte colony-stimulating factor as indicated, did not have undue nonhematologic toxicity. Dose-limiting toxicity was hematologic. At the recommended phase II/III dose (cyclophosphamide 1,000 mg/m(2)), grade 4 neutropenia was observed in 17% of all cycles and 31% of first cycles. Grade 3 or 4 thrombocytopenia was seen in only 1% of all cycles. The median number of cycles per patient was six (range, two to 11) for all patients enrolled. The response rate was 100% of 27 patients entered; 89% achieved a complete and 11% a partial response. Nineteen of 22 patients with bone marrow involvement had clearing of the marrow. Median duration of follow-up was more than 5 years; median overall and disease-free survival times have not been reached. Kaplan-Meier estimated 5-year overall survival and disease-free survival rates were 66% and 53%, respectively. CONCLUSION: The recommended dosing for this combination in patients with previously untreated low-grade lymphoma is cyclophosphamide 1, 000 mg/m(2) day 1 and fludarabine 20 mg/m(2) days 1 through 5. The regimen has a high level of activity, with prolonged complete remissions providing 5-year overall and disease-free survival rates as high as those reported for other therapeutic approaches in untreated patients.

Acquired immunodeficiency syndrome-associated non-Hodgkin's lymphoma.

The clinical picture is of aggressive high and intermediate grade lymphoma with extranodal presentation either as the first manifestation or during the course of HIV infection. The dramatic growth of tumors, leukopenia, opportunistic infections, and pre-existing AIDS-related problems of KS and chronic infections have made treatment extremely difficult. New regimens using short courses of chemotherapy, GM-CSF, and antiviral therapy have raised hopes that these measures will lead to improved survival.

Disseminated intravascular coagulation during surgery for scoliosis.

Disseminated intravascular coagulation (DIC) was recently observed intraoperatively in two patients who required correction and stabilization of scoliosis with Harrington instrumentation and spinal fusion. Despite negative bleeding history and normal preoperative coagulation parameters, each patient developed sudden massive bleeding soon after decortication of spinous processes and facet joints. Coagulation profile revealed decreased platelets, plasma coagulation factors, and fibrinogen in association with elevated fibrin split products. Cessation of all bleeding occurred within a few hours. There was rapid correction of the coagulation parameters with blood component replacement therapy, indicating that the defibrination was short-lived and had ceased by the end of surgery. A review of the literature revealed six similar cases of DIC occurring during elective orthopedic surgery, four of which involved spinal arthrodesis and/or bone grafts. We suggest that injury secondary to decortication or chipping at bone can serve as a trigger for defibrination. This type of DIC is self-limited, and ends with completion of the operation. The treatment is blood component replacement. Heparin should be avoided.

Phase II evaluation of vindesine in patients with non-small cell carcinoma of the lung.

Fifty-two patients with non-small cell carcinoma of the lung were treated iv with doses of vindesine at 3--4 mg/m2/week iv. Partial responses occurred in all histologic types in ten of 46 adequately treated patients, for an overall response rate of 22%. Patients not previously treated with chemotherapy had a higher response rate than those who had received prior chemotherapy (33% versus 12%). Reversible peripheral neuropathy occurred in all patients, and was generally of a mild to moderate degree. Mild leukopenia was seen frequently, with a median wbc nadir of 2900/mm3. As reported with the older vinca alkaloids, platelet-sparing with occasional episodes of thrombocytosis occurred with vindesine. It is concluded that vindesine is an active agent in non-small cell carcinoma of the lung and that further studies in previously untreated patients are indicated.