DEVEC metronomic schedule for aggressive B and T-cell lymphomas.
Abstract:
Background: Metronomic chemotherapy (MC) is an emerging approach in solid tumours. Since MC has been poorly investigated in aggressive lymphomas in 2011, we formulated a new oral MC regimen termed DEVEC (Deltacortene, Etoposide, Navelbine, Cyclophosphamide).
Methods: The DEVEC foresees an induction and a deescalated maintenance phase both consisting in 6 cycles. Rituximab is administered in CD20+ cases. Patients with aggressive B and T cell lymphomas, unsuitable for standard-chemotherapies, were enrolled in 6 Italian institutions. HIV+ and CNS involvement were excluded. Data were retrieved as of 31th January 2018 (EC approval n° 4640).
Results: 58 patients started DEVEC between October 2011 and October 2017: the median follow-up time is 23 months. Median age was 79 years (26–93): 22 (37.9%) were refractory and 20 (34.5%) relapsed after previous treatments; 16 (27.62%) were treatment-naïve. Histology: DLBCL = 41(70.7%); PTCL = 15 (25.9%) and MCL = 2 (3.4%). By comprehensive geriatric assessment, patients scored as FIT = 7 (12%), UNFIT = 16 (27.6%), FRAIL = 23 (39.6%); Super-Frail (SF) = 10 (17.2%). In 53 evaluable cases the overall hematologic toxicity was mild and manageable with growth factors. Extra-hematologic toxicity of grade ≥3 was reported in 12/53 patients (22.6%) and were all classified as SAE: 6/12 cases occurred in SF. 5/12 patients discontinued DEVEC and died respectively 0, 1, 4, 4 and 5 months after treatment stop. In 50/53 patients, evaluable for outcome, the ORR was 68% and CR rate 44%. In the Naïve subset (n = 14) ORR = 92.8% and CR+CRu = 64%; in the Relapsed subset (n = 16): ORR = 93.7%; CR = 62.5%; in the Refractory subset (n = 20) ORR = 30%; CR = 10%. The estimated median OS and PFS were 15 (95%CI = 9.17-20.83) and 13 (CI 95% = 2.07-23.93) months, respectively. No significant differences in OS and PFS were observed in DLBCL vs PTCL. The direct cost of drugs of the oral DEVEC schedule was estimated 930 and 817 Euro (year 2016) for a single induction and maintenance cycle, respectively.
Conclusions: To our knowledge this is the largest series of aggressive lymphoma treated with MC. DEVEC induced sustained CR in a substantial proportion of patients with very poor outlook and deserves further studies in aggressive lymphomas.
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