Dose Dense and Dose Intense ABVD (dd-di ABVD) in Advanced and Intermediate-Stage Hodgkin’s Lymphoma (HL).

ABVD is still considered the standard therapy for HL being a good balance of efficacy and tolerability. Here we report the 3-yr results of a phase 2 study which explore the possibility to ameliorate the performance of this (g)old schedule. Modifications of the standard ABVD and strategy concepts :

1. Each patient received a total of 6 cycles

2. For advanced stage, Adriamycin (ADM) was escalated from 50 to 70 mg/m2 in the cycles 1,2,3,4.

3. Intermediate stage patients (pts) were treated without the dose escalation of ADM.

4. The cumulative doses of ADM were 380 (advanced-) and 300 mg/m2 (intermediate-stage).

5. The inter-cycle period was shortened from 28 to 21 days for all 6 cycles; the 4 drugs were delivered at d 1 and 11 of each cycle.

6. Primary G-CSF was given from d4 to d8, and from d14 to d18 of each cycle.

7. The therapy program was driven by interim-FDG-PET. Normalisation of PET at the end of 2nd cycles was indicator of early complete response (CR), while the persistence of PET+ lesion(s) at the end of the 4th cycle was indicator of failure and consequently the treatment was shift to a salvage therapy

8. Consolidation Radiotherapy was reserved only for bone lesions.

From June 2004 to May 2006 fifty-eight pts were enrolled (Tab 1). On 20th August 2007 all patients have performed the interim-PET and 54/58 pts completed the treatment. Administered RDIs ranged between 1.10 to 1.44 (median 1.34) for DD-DI ABVD, and 1.18 to 1.34 (median 1.24) for DD ABVD. Hematologic toxicity was moderate and self-limiting with grade 3 or 4 neutropenia and anemia occuring in less than 20% of courses. Non-hematologic toxicity was generally mild to moderate. A limited number of G3-G4 reversible events determined the need for intervention (RBC’s trasfusions) or hospitalisation (pulmonary infections, GI and respiratory tracts, and neurological effects).The majority of pts presented a mild to moderate palmar-plantar erythrodysesthesia. Early cardiac toxicity was very mild. 55/ 58 obtained the early CR (95%) and 54/ 54 the CR (100%); a 60-yr old man died of pneumonia a month after the end of the last cycle still being in CR while one-site relapse occurred in a 27-yr old girl at ten month from the end of therapy. All the other pts are alive and disease-free. (tab 2 and fig 1). DD-DI ABVD and DD ABVD are feasible, well tolerated and highly active in advanced and intermediate HL: at 3 years from the beginning of the study these schedules confirm to be a promising strategy for optimal long-term results.

tab 1

Presentation features

.	N .	% .	GHSG .	.	NCI .	.
total	58	100%	N	%	N	%
advanced			36	62%	51	88%
intermediate			22	38%	7	12%
male	21	36%
age>45-yr	6	10%
bulky	21	36%
stage IV	17	29%
B symptoms	37	64%
extranodal	20	35%
ESR >50 mm	30	52%
LDH ratio>1	25	43%
IPS>3	20	35%
N sites>3	42	72%

.	N .	% .	GHSG .	.	NCI .	.
total	58	100%	N	%	N	%
advanced			36	62%	51	88%
intermediate			22	38%	7	12%
male	21	36%
age>45-yr	6	10%
bulky	21	36%
stage IV	17	29%
B symptoms	37	64%
extranodal	20	35%
ESR >50 mm	30	52%
LDH ratio>1	25	43%
IPS>3	20	35%
N sites>3	42	72%

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Tab 2

Response and Survival Data

.	N .	early CR .	CR .	TRM .	Relapse .	3-yr EFS .	3-yr OS .
median f-up 17 mos
	58 (100%)	55 (95%)	54/54 (100%)	1 (2%)	1 (2%)	98%	98%
GHSG
advanced	36	35 (97%)	33/33 (100%)			100%	97%
intermediate	22	20 (91%)	21/21 (100%)			95%	100%
NCI
advanced	51	49 (96%)	48/48 (100%)			98%	98%
intermediate	7	6 (86%)	6/6 (100%)			100%	100%

.	N .	early CR .	CR .	TRM .	Relapse .	3-yr EFS .	3-yr OS .
median f-up 17 mos
	58 (100%)	55 (95%)	54/54 (100%)	1 (2%)	1 (2%)	98%	98%
GHSG
advanced	36	35 (97%)	33/33 (100%)			100%	97%
intermediate	22	20 (91%)	21/21 (100%)			95%	100%
NCI
advanced	51	49 (96%)	48/48 (100%)			98%	98%
intermediate	7	6 (86%)	6/6 (100%)			100%	100%

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Fig. 1

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Fig. 1

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