Salvage regimens for non- Hodgkin’s lymphoma – pro

Lay Summary: I discuss salvage regimens for agressive of intermediate relapsed or refractory lymphoma.

Aggressive non-Hodgkin’s lymphoma is difficult to handle once it relapses or becomes refractory to chemotherapy. Various second or third line chemotherapies, which are called salvage chemotherapy, were developed without promising results. Improvement in efficacy by adding relatively new agent, rituximab, to chemotherapy is now widely accepted in non-Hodgkin’s lymphoma.

The consensus is that people with relapsed disease should be treated with salvage chemotherapy. The first systematic review identified 22 phase II studies (1210 people overall; individual trials from 20–208 people) using 15 different combinations of cytotoxic drugs for conventional dose second line (salvage) chemotherapy. The most common included drugs were etoposide (20 studies), ifosfamide (14 studies), and methotrexate (11 studies). Other drugs included cisplatin (6 studies), cytarabine (4 studies), mitoxantrone (3 studies), bleomycin (3 studies), and mitoguazone (3 studies). All 22 studies revealed similar results, with second line combination chemotherapy frequently inducing remission in people with relapsed or refractory aggressive non-Hodgkin’s lymphoma. The second review also reported the use of rituximab in non-controlled trials (number of trials not reported). The reviews found that overall 60–70% of people with relapsed disease showed objective tumour responses. Complete remission was seen in 20–40% of people. However, these remissions were frequently short lived, with a maximum of 10% of responders remaining disease free after 3–5 years. The authors of the reviews were unable to conclude that any particular salvage chemotherapy regimen was superior to any of the others from the literature reviewed.

There are no randomized controlled trials comparing different conventional dose salvage chemotherapy regimens (PACEBOM, ESHAP, RICE, IVAC) in people with relapsed aggressive non-Hodgkin’s lymphoma. The consensus is that people with relapsed disease should be treated with salvage chemotherapy. One systematic review identified 22 phase II trials of various conventional dose salvage chemotherapy regimens. All regimens reported similar response rates and no single superior regimen can be identified. There are likewise no studies confirming or disproving the additive effect of Rituximab but it is a well reported regimen and no clinical trials are currently investigatong RICE vs ICE chemotherapy.However, it is not proven. A clinical trial (NCT00367497) of R-ESHAP is currently recruiting patients.

MEHMET AKIF ÖZTÜRK et al, Modified ESHAP as salvage chemotherapy for recurrent or refractory non-Hodgkin’s lymphoma: Results of a single-center study of 32 patients Chemotherapy (Chemotherapy) 2002, vol. 48, no5, pp. 252-258

BMJ – Clinical Evidence –

Kimby E, Brandt L, Nygren P, et al. A systematic review of chemotherapy effects in aggressive non-Hodgkin’s lymphoma. Acta Oncol 2001;40:198–212.

Barosi G, Carella A, Lazzarino M, et al. Management of nodal diffuse large B-cell lymphomas: practice guidelines from the Italian Society of Haematology, the Italian Society of Experimental Haematology and the Italian Group for Bone Marrow Transplantation. Haematologica 2006;91:96–103.

Jerkeman M, Leppä S, Kvaløy S, Holte H.ICE (ifosfamide, carboplatin, etoposide) as second-line chemotherapy in relapsed or primary progressive aggressive lymphoma–the Nordic Lymphoma Group experience.Eur J Haematol. 2004 Sep;73(3):179-82.

DifH. Tilly, M. Dreyling, and On behalf of the ESMO Guidelines Working Group Diffuse large B-cell non-Hodgkin’s lymphoma: ESMO Clinical Recommendations for diagnosis, treatment and follow-up Ann Oncol (2010) 21 (suppl 5): v172-v174.

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