Dice (Dexamethasone, Ifosfamide, Cisplatin, Etoposide) as Salvage Therapy in Non-Hodgkin's Lymphomas

Abstract

Between April 1988 and April 1992 we conducted a study of DICE (dexamethasone 10 mg q6h, ifosfamide 1 g/m², cisplatin 25 mg/m², etoposide 100 mg/m², and mesna uroprotection daily x 4 given every 28 days) in thirty six patients with intermediate or high-grade non-Hodgkin's lymphomas (NHL's). All patients had disease refractory to anthracycline-based chemotherapy and were ineligible for our dose intensive salvage chemotherapy program including autologous bone marrow transplant (ABMT). Twenty six men and 10 women aged 21–79 years (median 61) were given 100 courses of treatment in hospital. Twenty three patients had stage IV, 7 stage III and 6 stage II disease. Fourteen patients had bone marrow involvement and 11 had B symptoms. Thirty two patients had received only 1 previous chemotherapy regimen.

After a follow-up of 1–70 months (median 7), 8 of the 34 (23%) patients evaluable for response had complete remission (CR) of their disease for 8–70+ months (med 24) and 15/34 (44%) partial remission (PR) for 2–55+ months (med 13), giving an overall response rate of 67% (23/34). Eight of the 36 patients are alive 34–70 months (median 48) after being enrolled on study, 6 of whom relapsed and responded to subsequent treatment. The estimated survival rates for all patients at 1 and 2 years are 50% and 36% respectively (Kaplan Meier). Response to prior chemotherapy was the only baseline characteristic statistically predictive (p = 0.04) of response to DICE by logistic regression analysis. Myelosuppression was the dose limiting toxicity. Two patients (5.5%) died from treatment induced sepsis. Fifteen (42%) patients developed a granulocyte nadir of < 0.5 × 10⁹/L and 15 (42%) patients developed a platelet nadir of < 50 × 10⁹/L. Nine patients required RBC transfusions and 8, platelet transfusions. Non-hematologic toxicity, in particular GI toxicity, was extremely mild, with 13/36 patients experiencing no toxicity and only 2/36 having grade III toxicity. No episodes of gross hematuria occurred and one patient developed an episode of transient blurred vision and delirium that resolved spontaneously.

In summary, DICE is an active regimen in refractory NHL's. It is a particularly well tolerated alternative for patients failing to meet the criteria for autologous bone marrow transplant (ABMT) by virtue of age or other adverse prognostic factors. Myelosuppression is dose limiting and higher doses with hematopoietic growth factors merit testing either alone or in combination with ABMT. Incorporation of DICE into front-line regimens for high risk patients should be considered.

Key Words:

• Non-Hodgkin's lymphoma
• refractory
• salvage therapy