Combination of idarubicin, vinblastine, dacarbazine, and gemcitabine ( IVDG ) as therapy for elderly patients with H odgkin lymphoma with cardiac and pulmonary comorbidity

Abstract

Introduction: Elderly people comprise from 15% to 35% of all newly detected patients with Hodgkin's lymphoma (HL). The choice of treatment for patients over 60 years demands much more personalized approach than in younger ones. The ABVD regimen, though performing acceptable hematologic toxicity and efficiency, is associated with 24% risk of pulmonary toxicity induced by bleomycin and 18% mortality associated with treatment rate in patients ≥60 years of age. More intensive programs are associated with even higher mortality rate in this age group. This trial was aimed to compare efficacy and toxicity of the combination of idarubicin, vinblastine, dacarbazine, and gemcitabine (IVDG) and the ABVD regimen. Methods: Single‐center, prospective, controlled, randomized noninferiority study was started in 2009. All patients over 60 years with newly diagnosed HL were included, regardless of the number and severity of comorbidities. The median age was 67 in the ABVD group and 70 in the IVDG group. Both groups were balanced by stage, IPS, other prognostic factors of HL, the number of cases with chronic heart failure (NYHA 2‐3), and chronic obstructive pulmonary disease. Number of cases with coronary heart disease was higher in the IVDG group‐16 compared to 8 in the ABVD group (P = .04). Seventeen patients received ABVD therapy, 20 patients‐IVDG regimen: idarubicin 5 mg/m2 IV days 1, 15, vinblastine 5 mg/m2 IV days 1, 15, dacarbazine 375 mg/m2 IV days 1, 15, gemcitabine 800 mg/m2 IV days 1, 15. Cycles were repeated every 14 days. In cases of severe (grade ≥ 3) hematologic toxicity doses gemcitabine and dacarbazine were reduced by 30% and 20%, respectively. Radiotherapy 30 Gy was performed on residual tumor masses only in patients with partial remission: n = 5 (25%) in IVDG group and n = 8 (47%) in ABVD group (P = .26). Results: Frequency of complete (CR) and partial (PR) responses did not significantly differ between IVDG and ABVD groups: CR was diagnosed in 14 and 10 patients, respectively (P = .5); PR‐in 3 and 4 patients, respectively (P = .7). Five‐year overall survival rate was ‐49% in the IVDG group vs ‐22% in the ABVD group (P = .41). In both groups, no infectious or hemorrhagic complications were diagnosed. Grade 3 hematologic toxicity was observed in 4 (25%) patients in the IVDG group, and 3 patients received redused doses of gemcitabine and dacarbazine. Frequency of pulmonary fibrosis, detected by CT scans after the completion of therapy, was significantly lower in the IVDG group‐0 cases vs 4 (24%) in ABVD group ‐(P = .004). Conclusions: IVDG regimen can be offered as a first‐line therapy in elderly patients with HL, especially in those with concomitant cardiac or pulmonary diseases. The efficacy of the IVDG regimen appears comparable to ABVD, with more acceptable profile of pulmonary and cardiac toxicity.