Prednimustine in refractory non-Hodgkin's lymphoma: a phase II study of the Northern California Oncology Group.

Fifty-six patients with advanced non-Hodgkin's lymphoma (NHL) were entered into a phase II study of prednimustine, an ester of chlorambucil and prednisolone. All patients were refractory to extensive prior combination chemotherapy. Therapy with prednimustine, 100 mg/m2/day orally, was given for three consecutive days every 2 weeks. The overall response rate in 43 evaluable patients was 30% (13/43), with 9% (4/43) achieving complete response (CR) and 21% (9/43) achieving partial response (PR). In the favorable histology subgroup (23 patients), the response rate was 39% (9/23), with 4% (1/23) achieving CR and 35% (8/23) achieving PR. In the unfavorable histology subgroup (20 patients), responses were seen in 20% (4/20) with 15% (3/20) achieving CR, all in heavily pretreated diffuse histiocytic lymphoma. Toxicity of this regimen was mild, with leukopenia below 3,000/mm3 in 22% and thrombocytopenia below 90,000/mm3 in 16% of patients. A positive correlation was observed between response and hematologic toxicity, indicating the potential for a dose-escalation schedule in future trials. These data confirm activity of prednimustine in NHL refractory to standard treatment. In view of its relatively mild toxicity, we conclude that prednimustine is an appropriate agent to test in combination chemotherapy regimens in this group of lymphomas.

High-dose cisplatin with diethyldithiocarbamate (DDTC) rescue therapy: preliminary pharmacologic observations.

Diethyldithiocarbamate (DDTC), a chelating agent that is a major metabolite of disulfuram, has been proposed as a potential rescue agent to reduce toxicity following high-dose cisplatin (HDCP) therapy. In the present study, we examined the pharmacologic interaction of HDCP and DDTC given as rescue therapy. Total plasma platinum and ultrafiltrate platinum pharmacokinetics and DDTC levels were determined in six patients with advanced malignancies who received a total of 11 cycles of HDCP with DDTC rescue. HDCP therapy (200 mg/m2 per cycle) consisted of 100 mg/m2 reconstituted in 250 cc 3% saline and infused over 3 h on days 1 and 8 of each 28-day cycle. DDTC rescue at a dose of 4 gm/m2 was given by an i.v. infusion (duration 1.5-3.5 h), beginning 45 min after the completion of cisplatin infusion. Peak total and ultrafiltrate levels and cisplatin pharmacokinetics in this study were indistinguishable from those of previous studies using the same HDCP regimen without DDTC rescue. Ultrafiltrate or unbound plasma platinum was less than 10% of total plasma platinum concentrations and demonstrated a biphasic pattern of elimination. Levels of DDTC predicted to be chemoprotective (greater than 400 microM) were achieved with the dose and schedule used in this study. These data demonstrate that DDTC can be targeted to protective plasma concentrations without significantly altering plasma cisplatin pharmacokinetics and support the potential usefulness of DDTC as a rescue agent following HDCP therapy.

Prolymphocytic leukemia. Serial responses to therapy.

Prolymphocytic leukemia is a rare lymphoproliferative disorder characterized by marked lymphocytosis, massive splenomegaly, minimal lymphadenopathy, and poor prognosis. Previous reports have noted very short survival, and poor response to single agent alkylator chemotherapy. A small number of reports have shown response to combination chemotherapy regimens including Adriamycin (doxorubicin). A case of prolymphocytic leukemia with serial responses to combination chemotherapy and splenectomy resulting in significant prolongation of survival is reported.