THE EORTC-GELA TREATMENT STRATEGY IN CLINICAL STAGES I-II HL Results of the H9-F and H9-U trials (#20982)

Transcription

1 EORTC Lymphoma Group THE EORTC-GELA TREATMENT STRATEGY IN CLINICAL STAGES I-II HL Results of the H9-F and H9-U trials (#20982) J. Thomas, C. Fermé, E.M. Noordijk, H. Eghbali and M. Henry-Amar 7th International Symposium on Hodgkin Lymphoma, Cologne, Germany, November

2 EORTC trials on Hodgkin s lymphoma supradiaphragmatic CS I and II H1 H2 H5 H6 H7 H8 H

3 Prognostic factors EORTC Lymphoma Group H9 Favorable Unfavorable 1. Age < 50 years 50 years 2. B-symptoms A+ESR < 50 mm A+ESR 50 mm & elevated ESR B+ESR < 30 mm B+ESR 30 mm 3. Number of involved 1, 2 or 3 4 or 5 areas 4. Mediastinal-thoracic < (MT) ratio

4 H9-trials Hodgkin s lymphoma CS I/II LP nodular excluded S T R A T I F I C A T I O N F U EBVP if CR(u) x 6 36 Gy 20 Gy no RT 6 ABVD + IF- RT 4 ABVD + IF- RT 4 BEACOPP + IF- RT

5 H9-F&U trials patients enrolled N =

6 Results of the H9-F trial 783 patients enrolled from September 1997 to May 2004 median FU 60 months (7 to 105)

7 EBVP scheme Epirubicin 70 mg / m 2 i.v. day 1 Bleomycin 10 mg / m 2 i.v./i.m. day 1 Vinblastine 6 mg / m 2 i.v. day 1 Prednisone 40 mg / m 2 p.o. day cycle / 21 days

8 Response to treatment Status at the end of EBVP (# 761) CR / CR u 78 % (51% / 27%) PR 19 % No change - Progression 3 % Early death -

9 H9-F trial: stopping rules Cumulative number of failures Null hypothesis H9-F: No RT (92) Patients at risk Stopping rules > 20% of one of the followings: PR or Progression after EBVP, relapse after CR/CRu, early death, severe treatment-related toxicity or RX protocol violation

10 Progressions & relapses 36 Gy 20 Gy no RT Nodal involved Nodal uninvolved Extra nodal Unspecified Total

11 Proportion Failure-Free EORTC-GELA H9-F trial treatment failure-free survival October EBVP-IF RX 36Gy (239) 89% 6 EBVP-IF RX 20Gy (209) 85% 6 EBVP-no RX (130) 69% yr rate 36 Gy vs 20 Gy vs no RX: P < Gy vs 20 Gy: P = 0.19 Time since 1st CTx course, mo

12 Deaths 36 Gy 20 Gy no RT Prog. disease Treat.-related complication Second cancer AML Intercurrent 1 - -

13 1.0 EORTC-GELA H9-F trial overall survival 5-yr rate Proportion Surviving October EBVP-IF RX 20Gy (209) 100% 6 EBVP-IF RX 36Gy (239) 98% 6 EBVP-no RX (130) 97% P value = Time since 1st CTx course, mo

14 Results of the H9-U trial 808 patients enrolled from October 1998 to September 2002 median FU 67 months (4 to 105)

15 ABVD scheme Adriamycin 25 mg/m 2 i.v. day 1 & 15 Bleomycin 10 mg/m 2 i.v. day 1 & 15 Vinblastine 6 mg/m 2 i.v. day 1 & 15 Dacarbazine 375 mg/m 2 i.v. day 1 & 15 1 cycle / 28 days

16 BEACOPP-baseline scheme Bleomycin 10 mg/m 2 i.v. day 8 Etoposide 100 mg/m 2 i.v. day 1-3 Adriamycin 25 mg/m 2 i.v. day 1 Cyclophosphamide 650 mg/m 2 i.v. day 1 Oncovin (vincristine) 1.4 mg/m 2 i.v. day 8 Procarbazine 100 mg/m 2 p.o. day 1-7 Prednisone 40 mg/m 2 p.o. day cycle / 21 days

17 Chemotherapy-related toxicity Patients given ABVD ABVD BEACOPP x 6 x 4 x 4 Antibiotics 6% 5% 13% Transfusions 2% 2% 9% Growth factors 29% 25% 14% Hospitalization 11% 12% 22% S.A.E. 9% 10% 19%

18 Response to treatment (1) Status at the end of chemotherapy (# 713) ABVD ABVD BEACOPP x 6 x 4 x 4 CR / CRu 74% 71% 59% PR 23% 28% 39% No change 1% 1% 1% Progression 2% < 1% - Early death - - < 1%

19 Response to treatment (2) Status at the end of radiotherapy (# 727) ABVD ABVD BEACOPP x 6 x 4 x 4 CR / CRu 87% 87% 84% PR 8% 12% 13% No change 1% < 1% 1% Progression 3% 1% 2% Early death < 1% - < 1%

20 Progressions & relapses ABVD ABVD BEACOPP x 6 x 4 x 4 Nodal involved Nodal uninvolved Extra nodal Unspecified Total

21 Proportion Failure-Free EORTC-GELA H9-U trial treatment failure-free survival October yr rate 6 ABVD-IF RX (276) 91% 4 BEACOPP-IF RX (255) 89% 4 ABVD-IF RX (277) 85% P value = 0.27 Time since Randomisation, mo

22 Deaths (1) Progressive disease 22 Treatment-related complication 14 pneumopathy (2), septicemia (3), bleeding (1) severe pulmonary fibrosis (6), unsp. (2) Intercurrent disease 3 septicemia (1), pulmonary embolism (1) suicide (1) Second cancer AML, NHL 2 Unspecified 4 Total 45

23 Deaths (2) ABVD ABVD BEACOPP x 6 x 4 x 4 Prog. Disease Treat.-related complication Intercurrent 1-2 Second cancer NHL - AML Unspecified Total

24 1.0 EORTC-GELA H9-U trial overall survival 5-yr rate Proportion Surviving October ABVD-IF RX (276) 94% 4 ABVD-IF RX (277) 94% 4 BEACOPP-IF RX (255) 93% P value = Time since Randomisation, mo

25 Conclusions H9-F In favourable patients achieving a complete remission after 6 cycles of EBVP omission of involved field radiotherapy leads to an unacceptable failure rate with involved field radiotherapy, a dose of 20 Gy leads to similar results as a dose of 36 Gy

26 Conclusions H9-U In unfavourable patients reduction of the number of ABVD cycles from 6 to 4 leads to similar EFS and OS rates 4 cycles of BEACOPP-baseline are not more efficient than ABVD, but are more toxic