Bortezomib and CHOP in Patients With Advanced Stage Aggressive T Cell or Natural Killer (NK)/T Cell Lymphomas
Status:
Completed
Trial end date:
2009-10-01
Target enrollment:
Participant gender:
Summary
Peripheral T-cell lymphomas (PTCLs) are neoplasias from post-thymic T-cells at different
stages of differentiation and are a heterogeneous group of malignancies which present with
different morphological patterns, phenotypes, and clinical presentations.
These tumours have a striking epidemiological distribution with a lower incidence in Western
countries than in Asia. In Korea, PTCLs including T- or natural killer (NK)-cell lymphomas
constitute approximately 25 to 35% of all non-Hodgkin's lymphomas. This incidence is quite
similar to that of other Eastern Asian countries, including Japan, Hong Kong, and China.
Recent studies suggest that the T-cell phenotype is an independent significant prognostic
factor, with PTCLs having one of the lowest overall survival and failure-free survival rates.
Based on the investigator's experience, the overall complete remission rate was 61.2% (95%
confidence interval [CI]: 48.5-72.8%) and the 5-year probability of failure-free survival was
33.5%. Median survival of all patients was 45 months (range 0-64+ months) and the 5-year
probability of survival was 36.2%. Rassidakis et al. reported that expression of
pro-apoptotic proteins BAX and BCL-XS, may explain the poor response of many types of PTCL to
standard chemotherapy.
To overcome such poor outcome, the optimal therapy for PTCLs remains to be defined. However,
because of the rarity of the disease in Western countries, only a few trials have been
reported.
Bortezomib (Velcade) is a modified dipeptidyl boronic acid, and a reversible inhibitor of the
chymotrypsin-like activity of the 26S proteosome. Bortezomib may induce tumor cell apoptosis
or decreased bcl-2 associated drug resistance. Through phase II studies, single agent
bortezomib in patients with relapsed indolent and mantle cell lymphomas showed its activity.
And also preliminary data indicate that bortezomib can be safely administered in combination
with dose adjusted etoposide, prednisolone, vincristine, cyclophosphamide and doxorubicin
(EPOCH) chemotherapy. Therefore, it can be possible to improve the poor outcome of patients
with PTCLs by a combination of cyclophosphamide, doxorubicin, vincristine, prednisolone
(CHOP) with bortezomib as a first-line therapy.
Primary Hypothesis: Based on the clinical trials and experimental data, bortezomib can
overcome pro-apoptotic proteins BAX and BCL-XS induced drug resistance.