Effective salvage therapy for lymphoma with cisplatin in combination with high-dose Ara-C and dexamethasone (DHAP)

Abstract

Ninety patients with progressive recurrent lymphoma were treated with a combination of cisplatin 100 mg/m2 intravenously (IV) by continuous infusion over 24 hours, followed by cytosine arabinoside in two pulses each at a dose of 2 g/m2 given 12 hours apart. Dexamethasone, 40 mg orally or IV, was given on days 1 through 4. Vigorous hydration was reinforced by routine use of mannitol. Treatments were repeated at 3- to 4-week intervals for six to ten courses. Most patients had not achieved complete remission (CR) with prior therapies, which included Adriamycin (all patients) and methotrexate and VP-16 (58 patients). Median patient age was 55 years. Intermediate-grade lymphoma was the most frequent pathologic diagnosis. Seven patients died within two weeks of therapy; of the remaining 83 patients, 28 (34%) or 31% if all patients are considered, achieved CR, and 22 (26.5%) achieved partial remission (PR). Response was evident after the first two cycles of chemotherapy and appeared to be independent of the histopathologic type of lymphoma. To date, only eight of the complete responders have relapsed at a median follow-up of 11 months. The overall 2-year survival in 25%. Further analysis showed that patients with low tumor burden and normal lactic acid dehydrogenase (LDH) had a high CR response rate (67%) and a survival rate of 61% at 2 years. In contrast, patients with both high tumor burden and elevated serum LDH levels had a negligible CR rate, and only 5% are surviving at 1 year. Patients with either high tumor burden with normal LDH or low tumor burden with elevated LDH had an intermediate survival. Myelosuppression-related infection was the most frequent serious complication of this regimen (31%) and the cause of death of ten patients. Acute lysis syndrome was also observed in five patients with high tumor burden and was the cause of death in three of these patients. DHAP has proven to be an effective non-crossresistant regimen for patients with relapsing or refractory lymphoma, particularly for patients who have favorable prognostic characteristics.

Ifosphamide, etoposide and epirubicin is an effective combined salvage and peripheral blood stem cell mobilisation regimen for transplant‐eligible patients with non‐Hodgkin lymphoma and Hodgkin disease

“…Myelosuppression was the major toxicity noted in this study, although renal impairment also occurred in a significant number of patients, as two out of 39 patients had severe renal failure. In relapsed HD similar response rates of 47% have been described following DHAP therapy (Velasquez et al , 1988; Rapoport et al , 1993). The second‐generation cisplatin‐containing regimens ESHAP (etoposide, Solu‐Medrol, cytarabine, cisplatin) (Velasquez et al , 1994; Watts et al , 2000) and ASHAP (adriamycin, Solu‐Medrol, high‐dose cytarabine, cisplatin) (Velasquez et al , 1995; Rodriguez et al , 1999) showed major response rates, which were at least as good and exhibited less myelotoxicity.…”

Comparative toxicities of 3 platinum‐containing chemotherapy regimens in relapsed/refractory lymphoma patients

“…The dexamethasone‐High dose aracytine (cis)platin (DHAP) regimen combining dexamethasone, cisplatin, and cytarabine is one of the most widely used, showing an overall response rate of 50% to 70% and 60% to 85% for, respectively, non‐Hodgkin and Hodgkin lymphoma. Rituximab is usually added to the DHAP regimen leading to higher response rates for patients with CD20 B‐cell lymphoma, and this regimen might provide better results in patients with a given diffuse large B‐cell lymphoma subtype .…”

“…However severe toxicities are often reported, requiring discontinuation and adjustment of the treatment. Among them, renal toxicity constitutes a major concern, with various incidences depending on the studies . Renal insufficiency was reported in 20% of patients with relapse or refractory lymphoma and remained persistent in 6.6% of them .…”

“…Among them, renal toxicity constitutes a major concern, with various incidences depending on the studies . Renal insufficiency was reported in 20% of patients with relapse or refractory lymphoma and remained persistent in 6.6% of them . Gisselbrecht et al observed 6% of grade III to IV renal failure after rituximab‐DHAP (R‐DHAP) regimen in patients with relapsed large B‐cell lymphoma …”

“…The common toxicity of DHAP, DHAOX, and ICE regimens remains the myelosuppression with grade III to IV neutropenia or thrombopenia varying between 20% and 75% . Nevertheless, platinum salts used in salvage therapy (cisplatin, carboplatin, and oxaliplatin) have different toxicity profiles.…”