High-dose etoposide and cyclophosphamide without bone marrow transplantation for resistant hematologic malignancy

Area of Science:

• Hematology
• Oncology
• Pharmacology

Background:

• Resistant hematologic malignancies pose a significant treatment challenge.
• Identifying effective salvage chemotherapy regimens is crucial for improving patient outcomes.

Purpose of the Study:

• To explore the activity of high-dose cyclophosphamide and etoposide in patients with resistant acute leukemia or lymphoma.
• To determine the maximum tolerated doses of this combination without the need for bone marrow transplantation.

Main Methods:

• Seventy-five patients with resistant hematologic malignancies received escalating doses of cyclophosphamide and etoposide.
• Etoposide was administered via continuous infusion (1.8–4.8 g/m²), and cyclophosphamide (150–200 mg/kg) over 3–4 days.
• Dose-limiting toxicity was assessed, with mucosal toxicity identified at the highest dose level.

Main Results:

• Severe but reversible myelosuppression occurred at all dose levels.
• The maximum tolerated dose combined etoposide 4.2 g/m² with cyclophosphamide 200 mg/kg.
• Overall response rates included 35% complete responses (CR) and 16% partial responses (PR).
• Seventeen of 40 (42%) patients with acute myelogenous leukemia (AML) achieved CR, including 30% with prior high-dose cytosine arabinoside resistance.

Conclusions:

• High-dose cyclophosphamide and etoposide is an active regimen in resistant hematologic neoplasms.
• Bone marrow transplantation is not necessary following treatment with the maximum tolerated doses of this combination.
• The observed responses in patients with high-dose cytosine arabinoside-resistant AML suggest a lack of complete cross-resistance.