Long-term Results of a Multicenter Randomized, Comparative Trial of Modified CHOP versus THP-COP versus THP-COPE Regimens in Elderly Patients with Non-Hodgkin's Lymphoma

Abstract

In treating elderly non-Hodgkin's lymphoma (NHL) patients, it is particularly important to use drugs that have a low incidence of adverse events and high efficacy. In this multicenter study, THP (pirarubicin)-COP (cyclophosphamide, vincristine, and prednisolone) was compared to two thirds dosage of full CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) regimen with regard to both adverse events and efficacy. For a third group, etoposide (E) was added to the THP-COP regimen (THP-COPE) in order to achieve high dose-intensity. Subjects were 486 previously untreated patients, aged 65 or older (range, 65-92 years; median, 74 years), with NHL. Subjects were randomly assigned to receive THP-COP, two thirds CHOP, or THP-COPE. Four hundred and forty-three patients were assessed for response and followed for 8 years after the last subject registered. The complete remission rates for the THP-COP, CHOP, and THP-COPE groups were 42.5%, 41.4%, and 48.0%, respectively. There was no difference in overall survival or progression-free survival among these 3 groups. In aggressive lymphoma, there was also no difference in complete response (CR) rate (45.3% in THP-COP, 44.9% in CHOP, 48.0% in THP-COPE), overall survival, and progression-free survival among these groups. The 5- and 8-year survival rates for all patients were 29.4% and 18.7%, respectively. The 5- and 8-year survival rates for patients with aggressive lymphoma were 27.4% and 17.4%, respectively. Although long-term survival for patients with aggressive lymphoma on our regimens was not worse compared to previous reports, the CR rate was lower. Because severe adverse events were not observed, higher dose chemotherapy may be directed to achieve better CR rates. In patients with T-cell-type lymphoma, the CR rate was greater after treatment with THP-COP (51.4%) or THP-COPE (57.7%) compared to treatment with CHOP (19.4%). Pirarubicin may be more useful for T-cell lymphoma than doxorubicin. Because adverse cardiac events were reported only in CHOP, adverse cardiac events might be low in the THP group.

Diffuse Large B-cell Lymphoma in the Elderly: A Review of Potential Difficulties

“…In these 2 studies, no difference in outcomes was observed between the different regimens with less cardiac toxicity observed with pirarubicin. However, the CR rates were lower than in other studies conducted worldwide with R-CHOP (48,62).…”

“…Other approaches to attenuate doses based on the CGA score have been developed but the benefits of this adaptation are difficult to evaluate as the studies failed to improve survival and have often generated inferior results (53,54). Pirarubicin (THP), an analog of doxorubicin, was used in 2 Japanese studies, a phase III study comparing CHOP, THP-COP, and THP-COPE (with etoposide) in the elderly and a retrospective analysis of 467 patients with aggressive NHL comparing THP-COP and CHOP (62). In these 2 studies, no difference in outcomes was observed between the different regimens with less cardiac toxicity observed with pirarubicin.…”

Complete remission of primary bilateral adrenal lymphoma achieved by Rituximab-CHOP chemotherapy

“…In a third group, etoposide (E) was added to the THP-COP regimen (THP-COPE) to achieve high dose intensity. In aggressive lymphoma, there were no differences in complete response (CR) rates (45.3% in THP-COP, 44.9% in CHOP, 48.0% in THP-COPE), overall survival, and progression-free survival among these groups [10].…”

Efficacy and Adverse Effects of Rituximab Combined with a TCOP Regimen in Patients with Untreated Diffuse Large B-cell Lymphoma and Follicular Lymphoma

“…A regimen of THP, cyclophosphamide CPA , vincristine VCR , and prednisolone PSL THP-COP or TCOP has been used to treat Non-Hodgkin lymphoma NHL in elderly patients [3][4][5] ; the Japanese Clinical Study Group of THP Lymphomas in the Elderly JGTLE reported the ef cacy of the same regimen in a large-scale, multicenter trial 5 . In addition, a recent phase II study of TCOP therapy in elderly patients aged 70 years or older with diffuse large B-cell lymphoma DLBCL showed a few side effects and good treatment ef cacy, particularly in patients with favorable prognostic factors 6 .…”