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/m2 in fixed infusion rate of 10 mg/m2/min, cisplatin 35 mg/m2 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.
Oncology Center, Mansoura University, Mansoura, Egypt, samanyshereef@yahoo.com.
Shereef
S
Elsamany
Mian U
MU
Farooq
Mostafa
M
Elsirafy
Sameh
S
Shamaa
Mona
M
Sakr
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D015331:Cohort Studies; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D003907:Dexamethasone / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D007262:Infusions, Intravenous; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D012074:Remission Induction; D016879:Salvage Therapy; D015996:Survival Rate; D055815:Young Adult; D000093542:Gemcitabine
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D019253:Proto-Oncogene Proteins c-bcl-2; D003841:Deoxycytidine; D003907:Dexamethasone; D002945:Cisplatin; D000093542:Gemcitabine