Substituting etoposide for doxorubicin in CHOP – pro

In general, RCHOP is standard of care for intermediate lymphoma, which grade 3 follicular lymphoma is. The CHOP combination CT, administered every 21 days, is the  standard for the treatment of advanced DLBCL for many years, with long-term disease-free survival in approximately 35% of patients. One of the newer developments is the addition of rituximab, a humanized anti-CD20 monoclonal antibody. The role of rituximab was first evaluated in elderly (>65 years) patients with DLBCL and the addition of rituximab to conventional CHOP (administered every 21 days, at standard doses) leads to a significant improvement in outcome. Eight cycles of rituximab-CHOP (R-CHOP) produced a complete response in 75% of patients versus 63% of CHOP alone (p = 0.005), with a significant 5-year survival benefit in terms of event-free (47 vs 29%), progression-free (54 vs 30%) and overall survival (58 vs 45%). The addition of rituximab did not substantially increase the toxicity of CHOP, even though a trend towards an increased risk of infections was observed after R-CHOP compared with CHOP. A cooperative American study in elderly patients comparing up-front CHOP with or without rituximab and with or without rituximab maintenance confirmed the GELA results, with a significant advantage for patients receiving rituximab, either as part of induction or maintenance therapy.

In regard to substituting etopposide:

Etoposide has mostly been explored as a component of salvage regimes for lymphoma. In such regimens it usually accompanies doxorubicin rather than substitutes for it, such as in EPOCH, BEACP. WHen there is concern for cardiotoxocity, epirubicin or mitozantrone is usually substituted for doxorubicin, not etopopside. Whether epirubicin can be substituted is under study in: CHOP Versus CEOP-Induced Cardiotoxicity in Patients With Aggressive B-Cell Lymphoma, NCT00854568. The use of liposome-encapsulated doxorubicin could be considered to be a more promising approach.There are phase II studies suggesting that the use of other non-doxorubicin regimens can be helpful.

Literature supporting Etoposide is limited. The R-EPOCT (rituximab with etoposide, vincristine, pirarubicine, cyclophosphamide, and prednisone) regimen, in which less cardiotoxic pirarubicine is used instead of doxorubicin, with granulocyte colony-stimulating factor (G-CSF) was administered to 20 patients with relapsed or refractory follicular lymphoma.The regimen was not cardiotoxic and was well tolerated.

Coiffier B, Lepage E, Brière J et al.: CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N. Engl. J. Med. 346, 235-242 (2002).
Feugier P, van Hoof A, Sebban C et al.: Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: A study by the Groupe d’Etude des Lymphomes de l’Adulte. J. Clin. Oncol. 23, 4117-4126 (2005).
Habermann TM, Weller EA, Morrison VA et al.: Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J. Clin. Oncol. 24, 3121-3127 (2006).
Batist G, Ramakrishnan G, Sekhar Rao C et al. Reduced cardiotoxicity and preserved antitumor efficacy of liposome-encapsulated doxorubicin and cyclophosphamide compared with conventional doxorubicin and cyclophosphamide in a randomized multicenter trial of metastatic breast cancer. J Clin Oncol 2001; 19: 1444–1454.
Gaynor ER, Ultmann JE, Golomb HM, et al. Treatment of diffuse histiocytic lymphoma (DHL) with COMLA (cyclophosphamide, oncovin, methotrexate, leucovorin, cytosine arabinoside): a 10-year experience in a single institution. J Clin Oncol. 1985;3:1596-1604.
Chao NJ, Rosenberg SA, Horning SJ. CEPP(B): an effective and well-tolerated regimen in poor-risk, aggressive non-Hodgkin’s lymphoma. Blood. 1990;76:1293-1298.
Niitsu N, Khori M, Hayama M, Kajiwara K, Higashihara M, Tamaru J.
Phase I/II study of the rituximab-EPOCT regimen in combination with granulocyte colony-stimulating factor in patients with relapsed or refractory follicular lymphoma including evaluation of its cardiotoxicity using B-type natriuretic peptide and troponin T levels.Clin Cancer Res. 2005 Jan 15;11(2 Pt 1):697-702.

Participate in our Forums

To ask questions or participate in a discussion, please visit our Forums. You must LOGIN to participate.

Help Us Help Others

You can become a Site Sponsor. Or you may wish to support our work with a Donation.

Focused Articles For You

Lay Portal