Less Intensive Hodgkin’s Chemo Works Better

The modified-intensity groups came out noninferior for the primary endpoint of 5-year freedom from treatment failure compared with the usual eight-cycle escalated BEACOPP regimen.

Results were similar for progression-free survival.

But a post-hoc analysis of time to progression suggested the 2-week cycle regimen wasn’t as effective as the six-cycle regimen, with a 5-year time to progression of 87.7% versus 92.6% with eight cycles (P=0.016).

The shorter cycles also didn’t improve overall survival.

The lower mortality rate with the six-cycle group - at 4.6% versus 5.2% with the shorter eight-cycle regimen and 7.5% with the longer eight-cycle regimen - appeared to be mainly due to fewer treatment-related events and secondary cancers.

Anemia rates were similar between groups, but the group given eight cycles every two weeks had somewhat less leukopenia (70% versus about 90% in both other groups) and 2 to 3 times less thrombocytopenia.

On the other hand, neurotoxic effects and pulmonary toxic effects occurred more frequently with the accelerated-dosing group.

Overall, “the therapy-related death rate reported with six cycles of escalated BEACOPP compared favourably with ABVD at less than 1%,” the commentary pointed out.

Secondary malignancies occurred at a rate of 3.4% overall, similar to the roughly 3% rate previously reported for ABVD, the researchers noted.

The secondary cancer rate was higher, though, in the eight-cycle group on a 3-week schedule compared with the six-cycle group (P=0.02).

The number of secondary acute myeloid leukemias or myelodysplastic syndromes was lowest - at two - with the six-cycle group, eight with the eight-cycle regimen every 2 weeks, and 19 for the other eight-cycle group (P=0.0001 versus six cycles).

Fewer patients receiving additional radiotherapy due to PET scan guidance - just 11% compared with over 70% in a prior trial with escalated BEACOPP - would also be expected to result in fewer second solid tumors, the researchers noted.

The negative predictive value for PET at 12 months was 94.1%, supporting it as a prognostic tool in determining therapy, the group added.

Casasnovas and Coiffier suggested that a PET scan after the first two cycles of therapy could be useful or identifying candidates for de-escalation to ABVD, although further research will be needed to figure out which patients need less than six cycles of escalated BEACOPP.

The study was funded by Deutsche Krebshilfe and the Swiss Federal Government.

The researchers and commentators reported having no conflicts of interest to disclose.

Primary source: The Lancet
Source reference: Engert A, et al “Reduced-intensity chemotherapy and PET-guided radiotherapy in patients with advanced stage Hodgkin’s lymphoma (HD15 trial): a randomised, open-label, phase 3 non-inferiority trial” Lancet 2012; DOI: 10.1016/S0140-6736(11)61940-5.

Additional source: The Lancet
Source reference: Casasnovas O, Coiffier B “Escalated BEACOPP in advanced Hodgkin’s lymphoma” Lancet 2012; DOI: 10.1016/S0140-6736(12)60153-6.

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