RESUMEN
BACKGROUND: Capecitabine plus oxaliplatin (XELOX) has shown modest activity and tolerable toxicity in a phase II trial for biliary tract cancers (BTCs). Meanwhile, gemcitabine plus oxaliplatin (GEMOX) has been the reference arm in recent phase II and III trials for BTCs. We aimed to investigate the efficacy of XELOX versus GEMOX as first-line therapy for advanced BCTs. PATIENTS AND METHODS: In this open-label, randomized, phase III, noninferiority trial, we randomly selected patients with metastatic BCTs to receive GEMOX (gemcitabine 1000 mg/m2 on days 1 and 8, and oxaliplatin 100 mg/m2 on day 1) or XELOX (capecitabine 1000 mg/m2, twice daily, on days 1-14 and oxaliplatin 130 mg/m2 on day 1) as first-line treatment, given every 3 weeks, totaling eight cycles. The primary end point was to prove the noninferiority of XELOX to GEMOX in terms of 6-month progression-free survival (PFS) rate. RESULTS: In total, 114 patients randomly received GEMOX and 108 randomly received XELOX. The median PFS was 5.3 months for the GEMOX group and 5.8 months for the XELOX group. The 6-month PFS rate was 44.5% for the GEMOX group and 46.7% for the XELOX group. The 95% confidence interval of the 6-month PFS rate difference between both groups was -12% to 16%, meeting the criteria for noninferiority of XELOX to GEMOX. There was no difference in objective response (P=0.171) and median overall survival (P=0.131) between both groups. The most common grade three to four adverse events were neutropenia and thrombocytopenia. No patient died of treatment-related causes. The XELOX group had significantly lower frequencies of hospital visits than the GEMOX group (P<0.001). CONCLUSION: XELOX showed significant noninferiority to GEMOX in terms of 6-month PFS rate. Thus, XELOX could be an alternative first-line treatment of BCTs. TRIAL REGISTRATION: This study was registered in ClinicalTrials.gov (number NCT01470443).
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Sistema Biliar/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias del Sistema Biliar/patología , Capecitabina/administración & dosificación , Capecitabina/efectos adversos , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/análogos & derivados , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Oxaliplatino/administración & dosificación , Oxaliplatino/efectos adversos , Supervivencia sin Progresión , Tasa de Supervivencia , GemcitabinaRESUMEN
The aim of this study was to investigate the efficacy of antibiotic prophylaxis in patients undergoing autologous stem cell transplantation (ASCT) for multiple myeloma and non-Hodgkin lymphoma. Among 232 ASCT cases performed at the Asan Medical Center, 114 cases underwent treatment with ciprofloxacin, fluconazole, and acyclovir (between January 2001 and August 2005), while 118 cases were performed without antimicrobial prophylaxis (between February 2004 and June 2008). The two-rate χ2 test was applied to accommodate the differences in neutropenia duration. The incidence of febrile episodes was 9.8 cases per 100 person-days in the prophylactic group, while it was 16.2 cases in the no-prophylactic group (p<0.001). The rate of unexplained fever was 8.0 cases per 100 person-days in the prophylactic group, while it was 13.8 cases in the no-prophylactic group (p<0.001). The rate of clinically and microbiologically documented infection was 1.7 cases per 100 person-days in the prophylactic group, while it was 2.3 cases in the no-prophylactic group (p=0.404). There were fewer cases of methicillin-susceptible Staphylococcus aureus infection and a greater number of quinolone-resistant Escherichia coli in the prophylactic group compared with the no-prophylactic group (p=0.056 and p=0.040, respectively). The prophylactic antimicrobials reduced the incidence rate of febrile episodes, especially unexplained fever, despite there being no difference in the incidence of documented infection. Resistant microbe infection occurred more frequently in the prophylactic group.
Asunto(s)
Aciclovir/administración & dosificación , Antibacterianos/administración & dosificación , Quimioprevención/métodos , Ciprofloxacina/administración & dosificación , Fiebre de Origen Desconocido/prevención & control , Fluconazol/administración & dosificación , Trasplante de Células Madre/efectos adversos , Adolescente , Adulto , Anciano , Antifúngicos/administración & dosificación , Antivirales/administración & dosificación , Escherichia coli/aislamiento & purificación , Femenino , Fiebre de Origen Desconocido/epidemiología , Humanos , Huésped Inmunocomprometido , Incidencia , Masculino , Persona de Mediana Edad , Staphylococcus aureus/aislamiento & purificación , Resultado del Tratamiento , Adulto JovenRESUMEN
We investigated the feasibility of i.v. BU, CY and etoposide (BUCYE), followed by auto-SCT (ASCT) in patients with newly diagnosed primary central nervous system lymphoma (PCNSL). The planned treatment consisted of induction chemotherapy with five cycles of high-dose MTX and two cycles of high-dose cytarabine followed by conditioning with BUCYE (BU 3.2 mg/m², day -7 to day -5; CY 50 mg/kg, day -3 to day -2 and etoposide 200 mg/m², twice a day, days -5 and -4) and then ASCT. Between May 2005 and November 2008, 11 consecutive PCNSL patients were treated. All patients completed the treatment as planned, with no cases of treatment-related death or veno-occlusive disease. After BUCYE and ASCT, 10 patients achieved complete response (CR) or unconfirmed CR (CRu). Two patients, one partial response and one CRu, received further whole-brain radiotherapy, with all achieving CR. At a median follow-up of 25.0 months (8.8-50.7 months), six patients had relapsed, with a median event-free interval of 15.0 months (95% confidence interval, 4.5-25.6 months). Median survival time was not reached yet with a 2-year survival rate of 88.9%. The current treatment was feasible with a favorable tolerance profile. However, further regimen optimization is necessary because of high relapse rate.
Asunto(s)
Antineoplásicos/uso terapéutico , Busulfano/uso terapéutico , Neoplasias del Sistema Nervioso Central/terapia , Ciclofosfamida/uso terapéutico , Etopósido/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Linfoma/terapia , Adulto , Anciano , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Busulfano/administración & dosificación , Busulfano/efectos adversos , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Neoplasias del Sistema Nervioso Central/radioterapia , Terapia Combinada/efectos adversos , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Etopósido/administración & dosificación , Etopósido/efectos adversos , Estudios de Factibilidad , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Linfoma/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Recurrencia , Inducción de Remisión , Análisis de Supervivencia , Acondicionamiento Pretrasplante/efectos adversos , Acondicionamiento Pretrasplante/métodos , Trasplante AutólogoRESUMEN
Although patients with T-cell phenotype lymphomas are generally accepted to have worse prognosis than B-cell phenotype lymphomas, the studies comparing outcomes after autologous stem cell transplantation (ASCT) between peripheral T-cell lymphomas (PTCLs) and with diffuse large B-cell lymphoma (DLBCL) are few. In this study, we compared outcomes after ASCT between 23 patients with PTCLs and 54 patients with DLBCL. Univariate analysis showed that the timing of ASCT, complete response (CR) at ASCT, favorable lactate dehydrogenase/performance/stage, low/low-intermediate (L-LI) International Prognostic Index (IPI) and L-LI age-adjusted IPI (aaIPI) at ASCT were significant predictors of both OS and EFS. Multivariate analysis showed that CR and L-LI aaIPI at ASCT were favorable for both OS (hazard ratio (HR), 0.34; 95% CI, 0.14-0.81; P=0.016 and HR, 0.27; 95% CI, 0.12-0.57; P=0.001) and EFS (HR, 0.38; 95% CI, 0.17-0.85; P=0.020 and HR, 0.36; 95% CI, 0.17-0.77; P=0.008). B-cell or T-cell phenotype, however, had no impact on OS (HR, 0.56; 95% CI, 0.27-1.18; P=0.126) or EFS (HR, 0.62; 95% CI, 0.30-1.30; P=0.206). In conclusion, when compared to patients with DLBCL, patients with PTCLs did not have inferior outcomes after ASCT. T-cell phenotype itself may not have an effect on outcomes of PTCL patients who underwent ASCT.