Phase II study of low-dose fixed-rate infusion of gemcitabine combined with cisplatin and dexamethasone in resistant non-Hodgkin lymphoma and correlation with Bcl-2 and MDR expression

This study aims to assess the efficacy of low-dose fixed-rate infusion of gemcitabine, cisplatin and dexamethasone in resistant non-Hodgkin lymphoma (NHL) patients in addition to evaluating the prognostic value of B cell lymphoma 2 (Bcl-2) and multidrug resistant (MDR) expression in this cohort of patients. Patients with relapsed/refractory NHL following at least two chemotherapy regimens were enrolled. They received gemcitabine 800 mg/m 2 in fixed infusion rate of 10 mg/m 2 /min, cisplatin 35 mg/m 2 in days 1, 15 and dexamethasone 20 mg days 1–4, 15–18 every 28 day. Response to treatment, time to disease progression (TTP) and 1-year progression-free survival (PFS) were assessed together with their association with Bcl-2, MDR expression and other prognostic variables. Overall response to treatment was 32 % (14 % complete response). Median TTP and 1-year PFS were 2 months and 31.3 %, respectively. Predictors of response to treatment were early stage [odd ratio (OR) = 4.6, 95 % CI 1.3–16.4], low/low intermediate International Prognostic Index (IPI) (OR = 6.2, 95 % CI 1.2–31.7), negative/low Bcl-2 expression (OR = 6.2, 95 % CI 1.2–31.7) and negative/low MDR expression (OR = 18, 95 % CI 1.4–28.9). However, IPI status lost its value in multivariate analysis. TTP and 1-year PFS were significantly associated with Bcl-2 expression ( p = 0.04), tumor status before enrollment (relapse vs. refractory, p < 0.0001) and tumor stage ( p < 0.000). In multivariate analysis, clinical stage was the only predictor of TTP and 1-year PFS. Fixed-rate gemcitabine infusion with cisplatin and dexamethasone had reasonable activity in resistant NHL. Clinical stage, Bcl-2 and MDR expressions were predictors of response to treatment, while only clinical stage was associated with TTP and 1-year PFS.