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

• Published in: Medical oncology (Northwood, London, England) Vol. 31; no. 3; p. 872
• Main Authors: Elsamany, Shereef, Farooq, Mian U., Elsirafy, Mostafa, Shamaa, Sameh, Sakr, Mona
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.03.2014; Springer Nature B.V
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; ATP Binding Cassette Transporter, Sub-Family B; ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism; Cisplatin - administration & dosage; Cohort Studies; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Dexamethasone - administration & dosage; Drug Resistance, Neoplasm - drug effects; Female; Follow-Up Studies; Hematology; Humans; Immunoenzyme Techniques; Infusions, Intravenous; Internal Medicine; Lymphoma, Non-Hodgkin - drug therapy; Lymphoma, Non-Hodgkin - metabolism; Lymphoma, Non-Hodgkin - mortality; Lymphoma, Non-Hodgkin - pathology; Male; Medicine; Medicine & Public Health; Middle Aged; Neoplasm Staging; Oncology; Original Paper; Pathology; Prognosis; Proto-Oncogene Proteins c-bcl-2 - metabolism; Remission Induction; Salvage Therapy; Survival Rate; Young Adult; Bcl-2; Refractory; Relapse; MDR; Gemcitabine; Lymphoma
• ISSN: 1357-0560; 1559-131X
• DOI: 10.1007/s12032-014-0872-0

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.