RESUMO
BACKGROUND: There is limited information regarding the efficacy and long term safety of intrathecal injection of liposomal cytarabine in leukemic or lymphomatous meningitis. DESIGN AND METHODS: We studied 20 consecutive HIV-negative patients with leukemic or lymphomatous meningitis who were treated with intrathecal liposomal cytarabine between 2004 and 2007. We focused on efficacy and on any late effects of the drug. RESULTS: Twenty patients who received intrathecal liposomal cytarabine injection as part of their treatment; of these, 9 were alive and in complete remission at the end of the study. Median survival from the time of the first injection was 22.7 months (range, 0.5 to 64 months). Short-term toxicity related to intrathecal of liposomal cytarabine was observed in 2 cases; headache in 1 case and regressive facial palsy and diplopy in 1 case. Long-term toxicity was seen in 2 cases; clinical symptoms were urinary and fecal dysfunction with confusion in 1 case, and urinary dysfunction in 1 case. Both patients had been heavily pre-treated with neurotoxic drugs and neuraxis irradiation. CONCLUSION: In our experience, intrathecal liposomal cytarabine injections were convenient in the management of leukemic and lymphomatous meningitis, and can lead to long-term survival. Although neurotoxicity was rare, clinicians should exercise caution when retreatment is required in relapsing patients.
Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/uso terapêutico , Citarabina/efeitos adversos , Citarabina/uso terapêutico , Leucemia/tratamento farmacológico , Linfoma/tratamento farmacológico , Neoplasias Meníngeas/tratamento farmacológico , Adulto , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Citarabina/administração & dosagem , Feminino , Humanos , Injeções Espinhais , Lipossomos/química , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: We explored the potential overall survival (OS) benefit of bleomycin, etoposide, doxorubicin (Adriamycin), cyclophosphamide, vincristine (Oncovin), procarbazine, and prednisone (BEACOPP) over doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine (ABVD) in a pooled analysis of four randomized trials. PATIENTS AND METHODS: Primary objective was to evaluate the OS impact of BEACOPP using individual patient data. Secondary objectives were progression-free survival (PFS), secondary cancers, and use of autologous stem cell transplantation (ASCT). RESULTS: About 1227 patients were included. The 7-year OS was 84.3% (95% CI 80.8-87.2) for ABVD vs 87.7% (95% CI 84.5-90.2) for BEACOPP. Two follow-up periods were identified based on survival curves and hazard ratio (HR) over time. For the first 18 months, there was no difference. For the second period of ≥18 months, ABVD patients had a higher death risk (HRABVD vs BEACOPP = 1.59; 95% CI 1.09-2.33). A Cox model stratified by trial and evaluating the effect of treatment and International Prognostic Index (IPI) score as fixed effects showed that both were statistically significant (treatment, P = .0185; IPI score, P = .0107). The 7-year PFS was 71.1% (95% CI 67.1-74.6) for ABVD vs 81.1% (95% CI 77.5-84.2) for BEACOPP (P < .001). After ABVD, 25 secondary cancers (4.0%) were reported with no myelodysplasia (MDS)/acute myeloid leukemia (AML) compared to 36 (6.5%) after BEACOPP, which included 13 patients with MDS/AML. Following ABVD, 86 patients (13.8%) received ASCT vs 39 (6.4%) for BEACOPP. CONCLUSIONS: This analysis showed a slight improvement in OS for BEACOPP and confirmed a PFS benefit. Frontline use of BEACOPP instead of ABVD increased secondary leukemia incidence but halved the requirement for ASCT.