Treatment of Aggressive Non-Hodgkin’s Lymphoma With Dose-Intensified Epirubicin in Combination of Cyclophosphamide, Vincristine, and Prednisone (CEOP-100)

Abstract

Epirubicin is an agent with a lower incidence of cardiotoxicity and myelotoxicity compared with doxorubicin; and it is active in patients with non-Hodgkin's lymphoma (NHL). Our aim was to define the therapeutic efficacy and toxicity of dose-intensified epirubicin in combination with cyclophosphamide, vincristine, and prednisone (CEOP) in patients with diffuse large-cell NHL. Previously untreated patients aged between 15 and 75 years, with at least one measurable lesion, adequate liver, renal, cardiac functions, and no central nervous system involvement were included in the study. The planned chemotherapy regimen CEOP consisted of cyclophosphamide 750 mg/m2, epirubicin 100 mg/m2, and vincristine 1.4 mg/m2 intravenously on day 1 and 100 mg prednisone taken orally on days 1 to 5. Courses were repeated every 21 days. Patients with stage I and II received four cycles of chemotherapy followed by involved-field radiotherapy, and patients with stage III and IV received six cycles of chemotherapy followed by radiotherapy to bulky lymph node sites. Seventy-five patients were enrolled in the study. The complete response rate was 83.8%, and 72 patients were assessable for toxicity. The most common toxicity was myelosuppression; 13.9% of the patients had grade III-IV neutropenia. Severe mucositis, diarrhea, and emesis were uncommon (<10%). At a median follow-up period of 41 months, the 5-year progression-free survival and overall survival rates were 63.5% and 65.3%, respectively. Increasing the dose intensity of epirubicin can yield a similar complete response rate compared with the regimens used in NHL without significantly increasing the toxicity rate associated with chemotherapy. The role of dose-intensive epirubicin should be investigated further in future randomized trials.

Phase II Study of Cyclophosphamide, Epirubicin, Vincristine, Prednisone, and Etoposide (CEOP-E) for Aggressive Non-Hodgkin's Lymphoma

“…As such, less cardiotoxic, yet equally efficacious, anthracycline agent is preferred as a frontline drug for NHL. Epirubicin in combination with other chemotherapeutic agents exhibited 58.3-90% of CR rates and 61.8-63.5% of 5-yr DFS rate in the previous studies (20-22), which were similar therapeutic activity to doxorubicin in combination with other agents. However, epirubicin has a more favorable adverse effect profile with lower hematologic toxicity, mucositis, and cardiac toxicity (23).…”

Long‐term follow‐up of patients with intermediate or high‐grade non‐Hodgkin lymphoma treated with a combination of cyclophosphamide, epirubicin, vincristine, and prednisone

“…Consequently, the use of EPI may be particularly suitable for more aggressive treatments, based on its dose intensity and dose density, without the need for autologous stem cell transplantation or the support of growth factors 7. However, it has not yet been proved that the routine use of these more intensive regimens improves the outcome of patients with NHL, and it is likely that they would be beneficial only in certain limited patient populations 9–13…”

“…Therefore, cumulative high doses of EPI also can cause chronic irreversible cardiomyopathy, ultimately leading to congestive heart failure (CHF) that is qualitatively identical to CHF observed after high cumulative doses of DOX 7. However, EPI toxicity occurs at cumulative doses > 1000 mg/m 2 , considerably higher than the cumulative dose associated with DOX toxicity.…”

Prospective Randomized Study Comparing MEMID with a Chop-Like Regimen in Elderly Patients with Aggressive Non-Hodgkin’s Lymphoma

“…Other CHOP-like regimens with anthracycline analogues, such as epirubicin, were also tested. The CEOP 100 regimen has a satisfactory therapeutic activity and an acceptable hematological and extra-hematological toxicity profile [15, 16]. …”