advanced stages

First-Line Therapy for Patients with Advanced Hodgkin’s Lymphoma: Efficacy and Toxicity of Intensive ЕАСОРР-14 Program (NN Blokhin National Medical Cancer Research Center Data)

LYMPHOID TUMORS , ,

EA Demina1, AA Leont’eva1, GS Tumyan1, YuE Ryabukhina1, OP Trofimova1, NV Volkova1, YuI Pryamikova1, VM Sotnikov2, VB Larionova1, EG Medvedovskaya1, EV Paramonova1, LV Manzyuk1, NA Probatova1, NV Kokosadze1, EA Osmanov1

1NN Blokhin National Medical Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

2Russian Scientific Center of Radiology and Nuclear Medicine, 86 Profsoyuznaya str., Moscow, Russian Federation, 117997

For correspondence: Prof. Elena Andreevna Demina, MD, PhD, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel.: +7(499)324-90-89; e-mail: drdemina@yandex.ru

For citation: Demina EA, Leont’eva AA, Tumyan GS, et al. First-Line Therapy for Patients with Advanced Hodgkin’s Lymphoma: Efficacy and Toxicity of Intensive ЕАСОРР-14 Program (NN Blokhin National Medical Cancer Research Center Data). Clinical oncohematology. 2017;10(4):443–52 (In Russ).

DOI: 10.21320/2500-2139-2017-10-4-443-452

ABSTRACT

Aim. To assess the efficacy and toxicity of intensive 6 courses EACOPP-14 treatment with or without radiotherapy (RT) for advanced stages of Hodgkin’s lymphoma (HL).

Materials & Methods. From November 2009 to February 2015, 95 patients with advanced stages of HL (IIX–IIE, III–IV) aged between 17 and 50 years (median 29 years) were selected for the participation in the protocol ЛХМосква1-3. The study population consisted of 46.3 % men and 53.7 % women. The results of the treatment were assessed in 91 patients who have received more than 2 courses of EACOPP-14. The follow up period was at least 3 months after the receiving the therapy. Consolidation RT with a total dose of 30 Gy for residual tumor lesions and/or initially large tumors was performed after the chemotherapy.

Results. Complete remission was achieved in 82 (90.1 %) patients, partial remission in 2 (2.2 %), and the progression was observed in 7 (7.7 %) patients. The overall 4-year survival rate was 90.8 %, the progression-free survival was 88.2 %. The toxicity of the ЕАСОРР-14 program was slightly lower than that of 8 courses of ВЕАСОРРesc, and was comparable to the toxicity of other modifications of intensified ВЕАСОРР scheme. Hematological toxicity grade 3 and 4 was most commonly observed: leukopenia was observed after 64.9 % of courses, anemia — after 24 % of courses, thrombocytopenia — after 3.8 % of courses. The rate of infections did not singificantly differ and accounted for 24 %. The most frequent non-infectious complications were mucositis (21.1 %) and polyneuropathy (11.7 %). Complications resulted in the change of treatment in only 3 (3.01 %) of patients. The exclusion of bleomycine from the ЕАСОРР-14 program reduced the frequency of RT complications. Grade 3 pulmonitis developed in 4.5 % of cases, while radiation-induce pulmonary fibrosis verified by CT developed in 15.2 % of cases. The ЕАСОРР-14 6 courses program showed its high efficacy both with and without RT, high tolerance and the possibility of full administration for the majority of patients with the various stages of HL.

Conclusion. Current research showed the efficacy of treatment without RT for patients with advanced stages of HL with negative PET results and small (< 2.5 cm) residual tumors after intensive ЕАСОРР-14 program. This approach allowed to avoid a number of late treatment complications.

Keywords: Hodgkin’s lymphoma, advanced stages, intensive first-line chemotherapy.

Received: March 10, 2017

Accepted: June 23, 2017

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Treatment of Advanced Stage Hodgkin’s Lymphoma: Literature Review

REVIEWS , , , ,

AA Leont’eva, EA Demina

N.N. Blokhin Russian Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

For correspondence: Anna Aleksandrovna Leont’eva, graduate student, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel.: +7(499)324-90-89; e-mail: aurevoir-nut@yandex.ru

For citation: Leont’eva AA, Demina EA. Treatment of Advanced Stage Hodgkin’s Lymphoma: Literature Review. Clinical oncohematology. 2015;8(3):255–66 (In Russ).

ABSTRACT

Over the past decade, major research centers with large databases in Europe and the USA have conducted a comprehensive analysis of the effectiveness of treatment programs, delayed treatment-related complications and long-term survival of patients with advanced stage Hodgkin’s lymphoma. This analysis allowed us to develop new, more effective programs and introduce them into practical medicine, as well as to start searching for less toxic treatment options. However, in Russian scientific literature, this complex analysis has not been presented. Available publications and scientific investigations cover only some aspects of diagnosis and treatment of Hodgkin’s lymphoma or selectively discuss the problem of complications. The proposed literature review allows the reader to see the changes in the approach to management of advanced-stage Hodgkin’s lymphoma over the last 75 years: from absolutely pessimistic prognosis for the disease to modern high achievements with further improvement of treatment options for this disease.

Keywords: Hodgkin’s lymphoma, advanced stages, treatment, effectiveness of treatment, toxicity.

Received: February 20, 2015

Accepted: May 28, 2015

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International prognostic score in advanced Hodgkin’s lymphoma

LYMPHOID TUMORS , , , ,

K.D. Kaplanov1, A.L. Shipaeva1, V.A. Vasil’yeva1, E.G. Gemdjian2, I.V. Matveeva1, L.S. Tregubova1, T.U. Klitochenko1, K.V. Demidenko1, O.B. Kalashnikova1, G.U. Vyskub1, O.E. Golubeva1, O.V. Levina1, V.A. Orlov1, and E.A. Demina3

1 Volgograd Regional Oncology Clinic #1, Volgograd, Russian Federation

2 Hematology Research Center, RF Ministry of Health, Moscow, Russian Federation

3 N.N. Blokhin Russian Cancer Research Center, RAMS, Moscow, Russian Federation

ABSTRACT

Since chemotherapy of Hodkgin’s lymphoma was introduced in early 60s, it has undergone fundamental changes that were associated with dramatic improvement in the disease prognosis. Currently, the various intensive modifications of original BEACOPP, such as BEACOPP-14 and escalate BEACOPP, are among the most widely used for treatment of advanced Hodkgin’s lymphoma.

Initially, the International Prognostic Score (IPS) was developed for patients treated with MOPP and MOPP-ABVD protocols. We suggest that due to the well-known changing value of the various prognostic signs with protocols of different intensity, the significance of IPS for BEACOPP-based therapy should be reconsidered.

One hundred seventy two patients with advanced Hodgkin’s lymphoma were included in our trial. All these patients were treated at the Hematology department of Volgograd Regional Oncology Clinic #1. Treatment options were as follows: 64 (37%), 84 (49%), and 24 (14%) patients received intensive BEACOPP-based, standard BEACOPP, or ABVD therapy, respectively. The final data presented are related to the period up to June 30, 2012.

We retrospectively evaluated the treatment outcomes for each IPS group. To distinguish the most significant prognostic signs from all six IPS factors, we studied the impact of each factor on treatment efficacy.

The greatest difference in overall 3- and 4-year survival was observed between the groups of patients with IPS 0–1 and ³ 2; for IPS 0–1, 3- and 4-year overall survival rate was 93%; for IPS ³ 2, 3- and 4-year overall survival rate was 81% and 75%, respectively (p = 0.05). 3-year overall survival was significantly negatively affected by such factors as age over 45 (70% versus 87%, relative risk (RR) = 3.95% CI: 1.7–7, p = 0.01) and albumin level < 40 g/L (79% versus 88%, RR= 2.8, 95% CI: 1.2–6.8, p = 0.02). Overall 3-year survival rate in males (n = 91) and females (n = 81) was 80% and 88%, respectively (p = 0.09). We found no effect on overall and freedom-from-treatment-failure survival (FFTF) of such factors as hemoglobin levels, lymphocyte count, leukocytes count, and IV stage disease. With respect to overall survival, multivariate analysis showed the greatest significance of age (relative risk, RR =3.6, 95% CI: 1.8–7, p = 0.001) and albumin level (OR = 2.6, 95% CI: 1.1–6, p = 0.036).

Keywords: Hodgkin’s lymphoma, international prognostic score (IPS), advanced stages, overall survival (OS), freedom-from-treatment-failure survival (FFTFS), BEACOPP, ABVD

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