CEBOPP/VIML Followed by Radiotherapy for Intermediate- and Advanced-Stage Hodgkin’s Disease: A Long-Term Analysis.
Authors: Nowrousian M.R. , Ernst S. , Beling C. , Wiefelspuetz U. , Schuett P. , Poser M. , Mueller S. , Ebeling P. , Welt A. , Flasshove M. , Moritz T. , Metz K.A. , Stuschke M. , Seeber S. 
Published: April 2020

Introduction. To improve treatment results and minimize acute and late toxicity in patients (pts) with intermediate- or advanced-stage Hodgkins disease, a combined modality treatment consisting of a response-adapted chemotherapy (CTX) and radiotherapy (RTX) was used. G-CSF was added in pts who developed severe or prolonged neutropenia or infection during CTX. Patients and treatment. From 10/90 to 2/04, 189 consecutive pts (53% males, 47% females) with a median age of 33 yrs (range 16–78) without prior treatment were included. Inclusion criteria were intermediate stage (I–II with risk factor or IIIA without risk factor) or advanced stage (IIB or IIIA with risk factor or IIIB or IV). Pt characteristics: 2% stage I, 54% stage II, 26% stage III, 18% stage IV disease. 48% B-symptoms, 87% bulky tumors (=/&gt;5cm), 20% extranodal involvement, 14% spleen involvement, 65% high ESR, 31% abnormal LDH (&gt;240 U/L). CTX started with cyclophosphamide (400 mg/m2 d3,4), epirubicin (40 mg/m2 d1,2), bleomycin (30 mg d1,10, 3 cycles in all pts and 2 cycles in pts who were going to receive mediastinal irradiation), vincristine (2 mg d1,10), prednisone (100 mg/m2 d1-10), and procarbazine (60 mg/m2 d1-10) (CEBOPP) repeated every 3 wks. In pts with no residual tumor after 4 cycles, CEBOPP was continued for further 2 cycles. In pts with progressive disease during treatment with CEBOPP or partial remission (PR) after 4 cycles, therapy was switched to VP-16 (130 mg/m2 d1,3,5), ifosfamide (1300 mg/m2+mesna d1-5), methotrexate (70 mg/m2+leucovorin rescue d1,5) (VIML) repeated every 3 wks for 2–4 cycles. CTX was followed by RTX (30 Gy, 40 Gy in case of bulky disease or residual tumor) predominantly given to IF in stage I-II and stage III disease with &lt;3 involved regions.

Results. Median duration of CTX was 4 months. The most frequent treatment toxicities were alopecia, leukocytopenia, and peripheral neuropathy. 42% of pts needed G-CSF during CTX. Toxic deaths occurred in 2 pts (1%). 82% of pts received additional RTX. An overall response rate of 99%, including 70% complete remissions (no residual tumor or residual tumor&lt;/=2cm) and 29% partial remissions (residual tumor&gt;2cm) was achieved. With a median follow-up of 6 yrs, the probability of event-free survival (EFS) and overall survival (OS) for the entire group of pts is 82% and 87% at 10 yrs, respectively. The probability of EFS and OS for pts with intermediate stage (n=83) is 86% and 88% and for pts with advanced stage (n=106) 79% and 86%, respectively. Myelodysplasia occurred in 1 pt (0.5%) and secondary neoplasia possibly related to treatment as solid tumor in 6 (3%) and as non-Hodgkin lymphoma in 2 (1%) pts.

Conclusion. Based on these results, CEBOPP/VIML followed by RTX appears to be highly effective in achieving long-term EFS and OS in pts with intermediate- or advanced-stage Hodgkins disease. These data compare favourably with the results of recent studies reported for these groups of pts.