Treatment of patients with advanced or bulky Hodgkin disease with a 12‐week doxorubicin, bleomycin, vinblastine, and dacarbazine‐like chemotherapy regimen followed by extended‐field, full‐dose radiotherapy

Abstract

BACKGROUND This Phase II study was performed in patients with advanced or bulky Hodgkin disease (HD) to evaluate the results of a 7‐drug chemotherapy (CT) regimen that was administered over 12 weeks according to 2 randomized modalities followed by high‐dose lymph node irradiation. METHODS From 1990 to 1996, 162 patients with HD at clinical stages (CS) I–III with bulky disease (mediastinal mass ratio ≥ 0.45 and/or unilateral or bilateral pelvic plus lumboaortic disease; 86 patients) or CS IV (76 patients) were randomized to receive the same cumulated dose of a CT regimen consisting of epirubicin (240 mg/m2), bleomycin (60 mg/m2), vinblastine (20 mg/m2), vincristine (4 mg/m2), cyclophosphamide (4000 mg/m2), etoposide (900 mg/m2), and methotrexate (180 mg/m2) plus methylprednisolone (1500 mg/m2) over 12 weeks either every 4 weeks (Arm Y, 79 patients) or every 3 weeks (Arm Z, 83 patients). Patients with disease in complete remission (CR) or partial remission after CT received extended‐field lymph node irradiation (involved areas, 40 grays [Gy]; noninvolved areas, 30 Gy). RESULTS Forty‐two percent of patients achieved a post‐CT CR, and 86% of patients achieved a CR after the completion of irradiation (there was no difference between Arm Y and Arm Z). Thirty‐five patients developed recurrent disease; most of those patients were in post‐CT partial remission. The 10‐year freedom from first progression rate was 63.9% (there was no difference between Arm Y and Arm Z). Thirty‐eight patients died: 24 patients from HD, 3 patients from CT‐related early sepsis, 1 patient from radiation‐induced pneumonitis, 6 patients from a second malignancy, and 4 patients from causes unrelated to treatment. The overall 10‐year survival rate was 76.7%. Survival was slightly higher among patients in Arm Y (83.3%) compared with patients in Arm Z (70.2%; P = 0.12). CONCLUSIONS No differences were found when the same amount of CT was delivered in three courses or in four courses. In 1997, because most recurrences of the H90‐A/B trial occurred in patients who achieved a post‐CT partial remission, the authors decided to reinforce the intensity of the initial CT and designed a new randomized study comparing two modalities of more intensive CT plus consolidative radiotherapy (H97‐LM trial). Cancer 2002;95:2169–79. © 2002 American Cancer Society. DOI 10.1002/cncr.10932

Comparison of initial characteristics and long-term outcome of patients with lymphocyte-predominant Hodgkin lymphoma and classical Hodgkin lymphoma at clinical stages IA and IIA prospectively treated by brief anthracycline-based chemotherapies plus extended high-dose irradiation

“…9,10,21 On the other hand, it was repeatedly demonstrated that the extent and the dose of RT play a major role in the genesis of solid tumors. [22][23][24] Finally, although the risk of cardiac complications associated with mediastinal RT did not reach statistical significance in the present study, it has now been shown that high-dose mediastinal RT has a significant negative impact on the development of cardiac events.…”

“…Patients were classified in CS IA to IVB according to the Ann Arbor criteria. [6][7][8][9][10] Of these 955 patients, 500 had CS IA and IIA.…”

“…The 219 patients with nonbulky CS IA or IIA received 3 cycles of either combination (ABVD, 113 patients; EBVM, 106 patients). 9,10 Finally, the 23 patients with bulky disease (characterized by an MMR Ն 0.45 or an infradiaphragmatic disease associating lumboaortic and pelvic nodes) were randomized to receive a multiagent CT including 7 drugs (plus methylprednisolone) delivered at the same cumulative dose over 3 months either in 3 courses (one every 4 weeks: arm Y, 14 patients) or in 4 courses (one every 3 weeks: arm Z, 9 patients). Radiation therapy given to CS IA and IIA Patients in both trials with complete remission (CR) or partial remission (PR) at completion of CT then underwent irradiation.…”

“…In these trials, patients were treated by a brief chemotherapy (CT) followed by an extended-field radiotherapy (RT) regimen. [6][7][8][9][10] Among the 955 patients with HL at clinical stage (CS) IA to IVB recruited in these trials, 74 patients were initially classified as having lymphocyte predominance according to the Rye classification. The pathologic material (lymph node biopsies) of these 74 patients was centrally reviewed and LPHL (according to the REAL/WHO definitions) was found in 44 patients.…”

Radiosensitising effect of electrochemotherapy with bleomycin in LPB sarcoma cells and tumors in mice

“…New understandings of mechanisms of its cytotoxicity have led to development of more potent and toxic therapeutic analogues [1]. Besides cytotoxic, BLM has also radiosensitising effect that was demonstrated in cells, experimental tumors as well as in the clinic [3-8]. …”