VIP (etoposide, ifosfamide and cisplatinum) as a salvage intensification program in relapsed or refractory Hodgkin’s disease

Abstract

Summary:Forty-two patients with refractory (15 patients) or relapsed (27 patients) Hodgkin's disease (HD) were included in a prospective single center study evaluating the efficacy of a regimen VIP combining etoposide 75 mg/m 2 /day days 1-5, ifosfamide 1.2 g/m 2 /day days 1-5 and cisplatinum 20 mg/m 2 /day days 1-5, one course every 4 weeks as salvage therapy in patients with refractory or relapsed Hodgkin's disease, potentially eligible for high-dose chemotherapy with reinjection of hematopoietic stem cells (HSC). If patients were considered chemosensitive after two courses of VIP, high-dose chemotherapy followed by the reinjection of HSC was planned. After two courses of VIP, 67% achieved an objective response including 38% complete responses. Overall, 28 patients went on to high-dose therapy with reinjection of HSC, and 46% of grafted patients are in a sustained complete remission. When the overall patient population is considered, 33% are in complete remission (CR) with a median follow-up of 37 months. A CR of less than 12 months and refractory disease were associated with a poor survival. These results showed that the VIP regimen is effective in relapsed or refractory HD and allows high-dose therapy to be given in the case of most responding patients. However, results in patients with refractory disease or a first complete remission of less than 12 months need to be further improved. Keywords: Hodgkin's disease; salvage therapy; VIP; etoposide; ifosfamide; cisplatinumThe prognosis for patients with Hodgkin's disease (HD) has dramatically improved with the use of modern extended-field radiotherapy and/or chemotherapy. With first-line chemotherapy, up to 80% of patients with advanced Hodgkin's disease achieve a complete remission (CR). 1-5 Despite optimal initial treatment, 20-50% of patients fail to enter remission or will relapse after achieving a complete response. [1][2][3][4][5][6][7] It has long been stated that patients who relapse after a first remission can be divided into two groups according to the length of their first remission. When patients relapse more than 1 year after the end of their first-line therapy, as many as 85% of them achieve a second complete remission when the same drug combination is used. 8-10 However, recent reports have shown that long-term disease-free survival at 15 years is achieved in only 20% of these favorable relapses. 8 Conversely, when patients relapse less than 12 months after their first CR or when they do not achieve a first CR, the results of conventional salvage therapy are worse and few long-term survivors are expected. 7,8,[11][12][13][14] High-dose chemotherapy followed by autologous hematopoietic rescue was considered a viable option because of good results achieved in a series of phase II trials. In refractory patients pooled with complete responders (Ͻ12 months), high-dose chemotherapy with reinfusion of HSC yielded CR rates of 40-80% with approximately 40% of patients free of disease at 3 years. [15][16][17][18][19][20][21][22][23][24][25] High-dose chemo...

Similar response rates and superior early progression‐free survival with gemcitabine, dexamethasone, and cisplatin salvage therapy compared with carmustine, etoposide, cytarabine, and melphalan salvage therapy prior to autologous stem cell transplantation for recurrent or refractory Hodgkin lymphoma

“…Although multiagent regimens like mini‐BEAM can produce high response rates and formed the induction chemotherapy and standard dose arms of the randomized trials reported by Linch et al4 and Schmitz et al,5 these and other regimens have significant shortcomings. Those shortcomings include myelosuppression with occasional fatal infection during neutropenia, requirement for hospitalization for drug administration, impairment of PBSC collection, and risk of secondary or late myeloid leukemia 6, 7, 9, 10, 12, 38, 39…”

“…There are many salvage regimens that have been reported for recurrent or refractory Hodgkin lymphoma,6–12 and several are platinum‐based 9–12. An ideal salvage regimen should produce a high response rate with acceptable hematologic and nonhematologic toxicity, and it should not impair the ability to mobilize peripheral blood stem cells (PBSCs) for autologous transplantation.…”

Standard therapy of advanced Hodgkin lymphoma

“…Although there was no difference in OS, FFTF was significantly improved in the ASCT group (55% versus 34%, P = .02). 22 Although there have been many published phase II studies reporting results of salvage regimens for relapsed or refractory Hodgkin lymphoma, [23][24][25][26][27][28][29][30][31][32][33] there are no RCTs and no consensus on the most effective second-line chemotherapy regimen. If the ultimate goal of salvage chemotherapy is to enable patients to proceed to ASCT, an ideal salvage regimen should produce a high response rate with acceptable hematologic and non-hematologic toxicity, and not impair the ability to mobilize peripheral blood stem cells for autotransplant.…”

Intermediate dose gemcitabine–cisplatin combination chemotherapy without treatment delay for cytopenia followed by autografting—a new standard of care in relapsed or refractory Hodgkin lymphoma?

“…Many regimens have been reported, often containing a platinum-based agent, but no single regimen has emerged as the accepted standard. Table 2 provides a summary of commonly used salvage regimens [3,[13][14][15][16][17][18]. All of these have inferior or comparable response rates to those reported here and where data is given the haematological toxicity is generally comparable or higher.…”