Rituximab, gemcitabine, cisplatin, and dexamethasone in patients with refractory or relapsed aggressive B-cell lymphoma.
ABSTRACT This study was conducted to evaluate the efficacy and safety of Rituximab, Gemcitabine, Cisplatin, and Dexamethasone (R-GDP) in relapsed or refractory aggressive B-Cell Non-Hodgkin's Lymphoma (NHL). Treatments consisted of rituximab 375 mg/m(2), i.v. on day 1; gemcitabine 1,000 mg/m(2), i.v. on days 1 and 8, dexamethasone 40 mg i.v. on days 1-4, and cisplatin 25 mg/m(2) i.v. on days 1-3, every 21 days. The primary end-points were the overall survival (OS) and progression-free survival (PFS). Secondary endpoints included response rate (ORR; CR) and toxicities. Eligible patients could then proceed to high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) or receive up to six treatment cycles. From January 2005 to December 2010, 50 successive patients at Tianjin cancer hospital lymphoma department were enrolled in this study. All patients were recurrent or refractory aggressive B-cell NHL, including diffuse large B-cell lymphoma (n = 30) and follicular lymphoma grade 3b (n = 20). The median follow-up time was 42 months (range, 12-70). After two cycles, the overall response rate was 72.0 %, with a CR/CRu rate of 56 %. The 2-year OS and PFS of all patients were 70.0 and 48.0 %, respectively. Grade III-IV neutropenia and thrombocytopenia occurred in 34 and 40 % of patients, respectively. Twenty-one patients (42 %) proceeded to ASCT. Higher International Prognostic Index and refractory disease were independently associated with worse survival and progression-free survival. R-GDP chemotherapy in patients with refractory or relapsed aggressive B-Cell NHL was effective as a salvage therapy and helpful for HDC/ASCT.
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ABSTRACT: Salvage therapy for patients with refractory/relapsed B-cell non-Hodgkin lymphoma (NHL) is based on polychemotherapy, followed by high-dose therapy and autologous stem cell transplantation in eligible patients (HDT/ASCT). R-DHAP combines rituximab with cisplatin, cytarabine, and dexamethasone. We substituted cisplatin with oxaliplatin to avoid nephrotoxicity and retrospectively analyzed a large series of 91 patients with refractory/relapsed B-cell NHL to evaluate toxicities, response rates (RRs), and survival. Median age at R-DHAX (rituximab/dexamethasone/cytarabine/oxaliplatin) treatment was 60 years (range, 28-82 years). Renal insufficiency was present in 18 patients. The most frequent histologic subtypes were diffuse large B-cell lymphoma (n = 42) and follicular lymphoma (n = 30). Seventeen patients (19%) were naive to rituximab at time of R-DHAX. Grade III/IV toxicities were mainly hematologic, including anemia (n = 9), neutropenia (n = 44), and thrombocytopenia (n = 47). Grade I/II neurologic toxicities, sensitive or motor, were observed, and these were mainly transient except for 3 cases of motor neuropathy associated with previous exposure to vincristine. Neither renal toxicities nor degradation of previous renal insufficiency were observed. The overall RR was 75%, with a complete RR of 57%, with no statistical difference between patients previously treated with rituximab versus without rituximab. At a median follow-up of 23 months, 2-year probability rates of overall survival and progression-free survival were 75% and 43%, respectively, with a significant difference between patients treated with HDT/ASCT and patients not eligible for HDT/ASCT. R-DHAX is an efficient regimen in patients with relapsed/refractory B-cell NHL even in elderly patients if hematologic toxicities are closely managed.Clinical lymphoma, myeloma & leukemia 08/2010; 10(4):262-9.
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ABSTRACT: We performed a pilot study to evaluate the effect of the high-dose gemcitabine-cisplatin combination in a brief weekly regimen in the treatment of primary refractory diffuse large cell lymphoma with high or high-intermediate clinical risk. Thirty patients refractory to first-line anthracycline-based chemotherapy were treated with a combination of gemcitabine (1.5 g/m(2) i.v.) and cisplatin (50 mg/m(2) i.v.) on days 1, 8, 22, 29, 42 and 49. No further treatment was administered. Complete response rate was 53%; and only two relapses have been observed at the last follow-up. Thus actuarial disease-free survival at the 3-year follow-up was: 87% (95% confidence interval, CI: 70-93%) and overall survival 53% (95% CI: 44-63%). Toxicity was mild, and treatment was well tolerated. No treatment-related death was observed. The gemcitabine-cisplatin combination appears to be promising in the treatment of refractory lymphoma patients, with a low toxicity. However, a longer follow-up is needed to confirm the results. In our opinion, prolonged chemotherapy (6-8 cycles) did not improve outcome. At present, we are testing if the use of monoclonal antibodies (anti-CD20) employed as maintenance therapy may improve disease-free survival and overall survival.Oncology 02/2004; 66(3):197-200. · 2.17 Impact Factor
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ABSTRACT: 2',2'-Difluorodeoxycytidine (dFdC; gemcitabine) is a new antineoplastic agent that is active against ovarian carcinoma, non-small-cell lung carcinoma, and head and neck squamous cell carcinoma. cis-diamminedichloroplatinum (CDDP; cisplatin) is used commonly for the treatment of these tumors. Because the two drugs have mechanisms of action that might be complementary, we investigated a possible synergism between dFdC and CDDP on growth inhibition. The combination was tested in the human ovarian carcinoma cell line A2780, its CDDP-resistant variant ADDP and its dFdC-resistant variant AG6000, the human head and neck squamous cell carcinoma cell line UMSCC-22B, and the murine colon carcinoma cell line C26-10. The cells were exposed to dFdC and CDDP as single agents and to combinations in a molar ratio of 1:500 for 1, 4, 24, and 72 h with a total culture time of 72 h. Synergy was evaluated using the multiple drug effect analysis. In A2780 and ADDP cells, simultaneous exposure to the drugs for 24 and 72 h resulted in synergism, but shorter exposure times were antagonistic. No synergism was found in the UMSCC-22B and C26-10 cell lines at prolonged simultaneous exposure. However, a preincubation with CDDP for 4 h followed by a dFdC incubation for 1, 4, 24, and 72 h was synergistic in all cell lines except C26-10 cells. A 4-h preincubation with dFdC followed by an incubation with the combination for 20 and 68 h was synergistic in all cell lines. Initial studies of the mechanism of interaction concentrated on the effect of CDDP on dFdCTP accumulation and DNA strand break formation. In all cell lines, CDDP failed to increase dFdCTP accumulation at 4- or 24-h exposure to dFdC; in two cell lines, CDDP even tended to decrease dFdCTP accumulation. Neither dFdC nor CDDP caused more than 25% double strand break formation, whereas in the combination, CDDP even tended to decrease this type of DNA damage. The synergistic interaction between the two drugs is possibly the result of dFdC incorporation into DNA and/or CDDP-DNA adduct formation, which may be affected by each other.Clinical Cancer Research 04/1996; 2(3):521-30. · 7.84 Impact Factor