R-CHOP therapy alone in limited stage diffuse large B-cell lymphoma.

Feb 2013

Tomita N, Takasaki H, Miyashita K, Fujisawa S, Ogusa E, Matsuura S, Kishimoto K, Numata A, Fujita A, Ohshima R,Kuwabara H, Hagihara M, Hashimoto C, Takemura S, Koharazawa H, Yamazaki E, Fujimaki K, Taguchi J, Sakai R,Ishigatsubo Y.

Source

Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Abstract

Long-term observation has identified a pattern of continuing relapse in limited stage diffuse large B-cell lymphoma (DLBCL) treated by three cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) plus involved-field irradiation. We retrospectively analysed 190 untreated patients with limited stage DLBCL treated by R-CHOP alone. All the patients were scheduled to undergo primary therapy with six cycles of full-dose R-CHOP. Cases with a dose reduction of more than 20% were excluded from the study. Additional local irradiation was allowed in patients with partial response (PR). Five patients received additional local irradiation after PR at the end of the R-CHOP therapy. The median observation period was 52 months. Median age at diagnosis was 63 years. The responses to therapy were 180 complete responses, eight PR, and two progression of disease (PD). The 5-year progression-free survival and 5-year overall survival rates were 84% and 90%, respectively, both in plateau. During the observation period, 29 patients experienced PD. The progression sites were the primary sites in 15 patients, outside the primary sites in 10, and undetermined in four patients. These results suggest that the 'standard' strategy of three cycles of R-CHOP followed by involved-field radiotherapy for limited stage DLBCL could be effectively replaced by six cycles of R-CHOP alone.

PubMed

Treatment of diffuse large B cell lymphoma.

Dec 2012

Kwak JY.

Source

Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Korea.

Abstract

Diffuse large B cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma in all countries and all age groups. DLBCL is potentially curable, and the outcome of patients with DLBCL has completely changed with the introduction of therapy involving the monoclonal antibody rituximab in combination with chemotherapy. Nonetheless, relapse is detected after treatment with rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisolone in approximately 30% of patients. It has recently become clear that DLBCL represents a heterogeneous admixture of quite different entities. Gene expression profiling has uncovered DLBCL subtypes that have distinct clinical behaviors and prognoses; however, incorporation of this information into treatment algorithms awaits further investigation. Future approaches to DLBCL treatment will use this new genetic information to identify potential biomarkers for prognosis and targets for treatment.

Full text article:

KJIM

Aurora A inhibitor (MLN8237) plus Vincristine synergizes with Rituximab as a potential curative therapy in aggressive B-cell non-Hodgkin lymphoma.

Feb 2012

Mahadevan D, Stejskal A, Cooke LS, Manziello A, Morales C, Persky DO, Fisher RI, Miller TP, Qi W.

Source

Hematology/Oncology, The University of Arizona Cancer Center.

Abstract

PURPOSE:

Aurora A and B are oncogenic serine/threonine kinases that regulate mitosis. Over-expression of Auroras promotes resistance to microtubule targeted agents. We investigated mechanistic synergy by inhibiting the mitotic spindle apparatus in the presence of MLN8237 [M], an Aurora A inhibitor with either vincristine [MV] or docetaxel [MD] in aggressive B-NHL. The addition of rituximab [R] to MV or MD was evaluated for synthetic lethality.

EXPERIMENTAL DESIGN:

Aggressive B-NHL cell subtypes were evaluated in vitro and in vivo for target modulation and anti-NHL activity with single agents, doublets and triplets by analyzing cell proliferation, apoptosis, tumor growth, survival and mechanisms of response/relapse by gene expression profiling with protein validation.

RESULTS:

MV is synergistic while MD is additive for cell proliferation inhibition in B-NHL cell culture models. Addition of R to MV is superior to MD but both significantly induce apoptosis compared to doublet therapy. Mouse xenograft models of mantle cell lymphoma showed modest single agent activity for M, R, D and V with tumor growth inhibition (TGI) of ~10-15%. Of the doublets, MV caused tumor regression, while TGI was observed with MD (~55-60%) and MR (~25-50%) respectively. Although MV caused tumor regression, mice relapsed 20 days after stopping therapy. In contrast, MVR was curative, while MDR led to TGI of ~85%. PCNA, Aurora B, cyclin B1, cyclin D1 and Bcl-2 proteins of harvested tumors confirmed response and resistance to therapy.

Clinical Cancer Research