RESUMO
Based on centroblast frequency, follicular lymphoma (FL) is subdivided into grades 1-2, 3A, and 3B. Grade FL3A frequently coexists with FL1-2 (FL1-2-3A). Based on clinical trials, FL1-2 is treated with rituximab (R) or obinutuzumab plus bendamustine (B) or CHOP, while FL3B is treated with R-CHOP. In contrast, there are little data guiding therapy in FL3A. We present a retrospective, multicenter analysis of 95 FL3A or FL1-2-3A and 203 FL1-2 patients treated with R-CHOP or R-B first-line. R-CHOP facilitated a higher response rate (95% versus 76%) and longer overall survival (OS) (3-year OS 89% versus 73%, P = 0.008) in FL3A or FL1-2-3A, whereas the difference in progression-free survival (PFS) did not reach statistical significance. While transformation rates into aggressive lymphoma were similar between both groups, there were more additional malignancies after R-B compared with R-CHOP (6 versus 2 cases). In FL1-2, R-B achieved a higher 3-year PFS (79% versus 47%, P < 0.01), while there was no significant difference regarding OS or transformation. With the limitations of a retrospective analysis, these results suggest a benefit for R-CHOP over R-B in FL3A or FL1-2-3A. Confirmatory data from prospective clinical trials are needed.
Assuntos
Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Cloridrato de Bendamustina/administração & dosagem , Linfoma Folicular/tratamento farmacológico , Rituximab/administração & dosagem , Idoso , Estudos de Coortes , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Seguimentos , Humanos , Linfoma Folicular/diagnóstico , Linfoma Folicular/mortalidade , Masculino , Pessoa de Meia-Idade , Gradação de Tumores/métodos , Prednisona/administração & dosagem , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Resultado do Tratamento , Vincristina/administração & dosagemRESUMO
BACKGROUND: Induction chemotherapy (ICT) with docetaxel, cisplatin and fluorouracil (TPF) followed by radiotherapy is an effective treatment option for locally advanced head and neck cancer. This phase II study investigated the effectivity of a split-dose TPF ICT before surgery for locally advanced resectable (stage III/IVA) oral and oropharyngeal cancer. PATIENTS AND METHODS: Patients received TPF split on two dosages on days 1 and 8 per cycle (30 mg/m2 docetaxel, 40 mg/m2 cisplatin, 2000 mg/m2 fluorouracil per week). Responders (reduction tumor volume ≥30% after first cycle) received three 3-week cycles and non-responders only one cycle before surgery and postoperative radio(chemo)therapy (RCT). The primary endpoint was progression-free survival rate after 24 months. Secondary endpoints were amongst others overall survival, histopathological response to ICT, toxicity, quality of life and swallowing function. RESULTS: Fifty-four patients (91% stage IVA, 87% male, 72% oropharyngeal cancer, 70% responders) were eligible for a per-protocol analysis. The progression-free survival rate after 24 months was 88.5% for responders and 60.6% for non-responders (P = 0.005). The overall survival rate after 24 months was 97.3% for responders and 73.7% for non-responders (P = 0.032). The rate of histopathological complete remission of the primary tumor was higher in responders (P = 0.015). High-risk classification for postoperative RCT was lower in responders (P < 0.0001). The most common grade 3+ adverse event was neutropenia in 26% of patients during ICT and mucositis in 13% during postoperative RCT. During treatment and follow-up quality of life and swallowing function was not different between responders and non-responders. CONCLUSION: Patients with oral and oropharyngeal cancer responding to split-dose TPF before surgery and postoperative RCT show good oncological results. The tri-modal treatment regime was well tolerated. ICT using tumor response as criterion for duration of ICT before surgery of oral and oropharyngeal cancer merits additional investigation in a phase III study. CLINICAL TRIAL NUMBER: NCT01108042.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/terapia , Neoplasias Bucais/terapia , Neoplasias Orofaríngeas/terapia , Idoso , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirurgia , Cisplatino/administração & dosagem , Terapia Combinada , Deglutição , Docetaxel , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/cirurgia , Neoplasias Orofaríngeas/tratamento farmacológico , Neoplasias Orofaríngeas/radioterapia , Neoplasias Orofaríngeas/cirurgia , Cuidados Pós-Operatórios , Qualidade de Vida , Análise de Sobrevida , Taxoides/administração & dosagemRESUMO
BACKGROUND: The aim of this exploratory subgroup analysis of the fluorouracil, oxaliplatin, docetaxel (FLOT)65+ trial was to determine tolerability and feasibility of perioperative chemotherapy in elderly, potentially operable esophagogastric cancer patients. METHODS: Patients aged ≥65 with locally advanced esophagogastric adenocarcinoma were randomized to perioperative chemotherapy consisting of four pre- and four postoperative cycles of infusional 5-FU, leucovorin, and oxaliplatin (FLO) without or with docetaxel 50 mg m(-)(2) (FLOT), every 2 weeks. RESULTS: Forty-four patients with a median age of 70 years were randomized and 43 patients started preoperative chemotherapy (FLO, 22; FLOT, 21). Thirty-eight (86.4%) patients completed four cycles of preoperative chemotherapy and 32 (74.4%) proceeded to surgery, with 67.4% R0 resections on intent-to-treat analysis (90.1% of the 32 patients who underwent resection). Median overall survival was not reached and median progression-free survival (PFS) was 17.3 months. Compared with the FLO group, the FLOT group showed a trend towards an improved median PFS (21.1 vs 12.0 months; P=0.09), however, associated with increased chemotherapy related toxicity. No perioperative mortality was observed. Postoperative morbidity was observed in 46.9% of patients (FLO, 35.3%; FLOT, 60%). CONCLUSION: Neoadjuvant FLO or FLOT may offer a reasonable chance of curative surgery in elderly patients with locally advanced resectable gastroesophageal cancer. However, the increase in side effects with the FLOT regimen and postoperative morbidity should be carefully considered when an intensive chemotherapy regimen is planned.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Docetaxel , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Estudos de Viabilidade , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Leucovorina/administração & dosagem , Masculino , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Assistência Perioperatória , Prognóstico , Estudos Prospectivos , Qualidade de Vida , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Taxoides/administração & dosagemRESUMO
BACKGROUND: The prognostic role of matrix metalloproteinase-9 (MMP-9) in metastatic gastric cancer has not been validated. PATIENTS AND METHODS: We carried out a molecular analysis in 222 metastatic gastric cancer patients obtained from clinical trials. We assessed the messenger RNA (mRNA) expression of MMP-9, vascular endothelial growth factor receptor-A, and epidermal growth factor receptor in a training cohort of 130 patients and conducted an independent validation in 92 patients. Automated RNA extraction from paraffin and RT-quantitative PCR was used. Immunohistochemistry for MMP-9 and diverse immune cell infiltrates was conducted. RESULTS: In the training cohort, only MMP-9 significantly correlated with patient's survival. At the cut-off with the highest predictive value, 19% of patients had MMP-9 expression above this cut-off and these showed a median survival of 3.6 months compared with 10.5 months (P=1.7e(-6)) in patients with lower expression. Corresponding 1- and 2-year survivals were 9% and 44% and 0 and 21%, respectively. The application of this cut-off to the validation cohort revealed similar distributions of overall survival according to MMP-9 expression on uni- (P<0.001) and multivariate analyses (P<0.001). No differences in survival according to MMP-9 below best cut-off were found. MMP-9 protein assessed by immunohistochemistry was not prognostic. CONCLUSION: MMP-9 mRNA expression above a certain cut-off level is associated with dismal survival.
Assuntos
Adenocarcinoma/enzimologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Expressão Gênica , Metaloproteinase 9 da Matriz/genética , Neoplasias Gástricas/enzimologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/mortalidade , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Cisplatino/administração & dosagem , Ensaios Clínicos Fase III como Assunto , Docetaxel , Receptores ErbB/genética , Receptores ErbB/metabolismo , Feminino , Fluoruracila/administração & dosagem , Humanos , Estimativa de Kaplan-Meier , Leucovorina/administração & dosagem , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Pessoa de Meia-Idade , Análise Multivariada , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Taxoides/administração & dosagem , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
BACKGROUND: Gemcitabine, oxaliplatin and 5-fluorouracil (5-FU) are active in biliary tract cancer and have a potentially synergistic mode of action and non-overlapping toxicity. The objective of these trials was to determine response, survival and toxicity separately in patients with bile duct cancer (BDC) and gallbladder cancer (GBC) treated with gemcitabine/oxaliplatin/5-FU chemotherapy. METHODS: Eligible patients with histologically proven, advanced or metastatic BDC (n=37) or GBC (n=35) were treated with gemcitabine (900 mg m(-2) over 30 min), oxaliplatin (65 mg m(-2)) and 5-FU (1500 mg m(-2) over 24 h) on days 1 and 8 of a 21-day cycle. Tumour response was the primary outcome measure. RESULTS: Response rates were 19% (95% CI: 6-32%) and 23% (95% CI: 9-37%) for BDC and GBC, respectively. Median survivals were 10.0 months (95% CI: 8.6-12.4) and 9.9 months (95% CI: 7.5-12.2) for BDC and GBC, respectively, and 1- and 2-year survival rates were 40 and 23% in BDC and 34 and 6% in GBC (intention-to-treat analysis). Major grade III and IV adverse events were neutropenia, thrombocytopenia, elevated bilirubin and anorexia. CONCLUSION: Triple-drug chemotherapy achieves comparable results for response and survival to previously reported regimens, but with more toxicity.
Assuntos
Adenocarcinoma/tratamento farmacológico , Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias da Vesícula Biliar/tratamento farmacológico , Adenocarcinoma/patologia , Adolescente , Adulto , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Neoplasias dos Ductos Biliares/patologia , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Neoplasias da Vesícula Biliar/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem , GencitabinaRESUMO
5-Fluorouracil (5FU) and capecitabine are two of the most frequently prescribed chemotherapeutic drugs for the treatment of patients with cancer. Administration of test doses of 5FU to eight patients heterozygous for the IVS14+1G > A mutation and five control patients showed that the AUC and clearance were weak parameters with respect to the identification of patients with a DPD deficiency. However, highly significant differences were observed for the terminal half life of 5FU between DPD patients and controls. Thus, a DPD deficiency could be predicted from 5FU blood concentrations measured after the administration of a test dose of 5FU.
Assuntos
Antineoplásicos/farmacocinética , Deficiência da Di-Hidropirimidina Desidrogenase , Di-Hidrouracila Desidrogenase (NADP)/genética , Fluoruracila/farmacocinética , Heterozigoto , Mutação/genética , Antineoplásicos/sangue , Antineoplásicos/uso terapêutico , Área Sob a Curva , Fluoruracila/sangue , Fluoruracila/uso terapêutico , Humanos , Taxa de Depuração Metabólica , Neoplasias/sangue , Neoplasias/tratamento farmacológico , Neoplasias/enzimologiaRESUMO
BACKGROUND: Combinations of gemcitabine-oxaliplatin, gemcitabine-5-fluorouracil (5-FU) and 5-FU-oxaliplatin have synergistic activity and nonoverlapping adverse effect profiles. This trial assessed efficacy and safety of the triple combination gemcitabine-oxaliplatin and infusional 5-FU in patients with locally advanced (n=11) or metastatic (n=32) pancreatic adenocarcinoma. PATIENTS AND METHODS: A total of 43 eligible patients were treated with intravenous infusions of gemcitabine (900 mg/m2 over 30 min), followed by oxaliplatin (65 mg/m2 over 2 h) and 5-FU (1500 mg/m2 over 24 h) on days 1 and 8 of a 21-day cycle. RESULTS: Among all 43 patients, the tumor response rate was 19% [95% confidence interval 7% to 30%]. Nine patients were nonassessable for response because they did not complete the first two cycles of chemotherapy due to rapid disease progression, early death or treatment refusal. One patient was lost to follow-up. Median time to progression and overall survival were 5.7 and 7.5 months. Principal grade III/IV toxic effects were leucopenia in 11 (2%), thrombocytopenia in 13 (2%), nausea in 13 (0%), anorexia 16 (7%) and sensory neuropathy in 18 (0%) of patients. Unexpected cardiotoxicity was observed in this trial. CONCLUSION: Response rates and survival of the three-drug combination compare favorably with single-agent gemcitabine, but do not exceed results for doublets.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Adenocarcinoma/secundário , Idoso , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Progressão da Doença , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Neoplasias Pancreáticas/patologia , Qualidade de Vida , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , GencitabinaRESUMO
Adult cutaneous Langerhans cell histiocytosis (LCH) is a rare disease. We report two cases illustrating the variability of the clinical presentation and the response to treatment. In both cases a remission was achieved: in one case a partial remission with psoralen plus UVA irradiation (PUVA) and methotrexate plus topical corticosteroid ointment; in the other case by treatment with thalidomide. Despite a therapeutic response, both patients later developed haematological malignancies: a chronic myelo-monocytic leukaemia and an acute lymphatic leukaemia. In conclusion, patients with adult cutaneous LCH should be monitored carefully so that a secondary malignancy is not overlooked.
Assuntos
Neoplasias Hematológicas/complicações , Histiocitose de Células de Langerhans/complicações , Adulto , Idoso , Humanos , MasculinoRESUMO
BACKGROUND: There is evidence that intensified variants of the classical 3-weekly CHOP-21 chemotherapy [cyclophosphamide (C), doxorubicin (H), vincristine (O), prednisone (P)] may improve treatment outcome in aggressive lymphoma. Three variants using either an addition of etoposide (CHOEP-21: 100 mg/m(2) on days 1-3), the shortening to 2-week intervals using recombinant human granulocyte colony-stimulating factor (rhG-CSF; CHOP-14) or both (CHOEP-14) are currently compared with CHOP-21 in the NHL-B trial of the German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL). To enable more extensive testing of these schemes we here characterise their practicability regarding schedule adherence, acute haematotoxicity and need for supportive treatment. PATIENTS AND METHODS: The trial included patients with normal lactate dehydrogenase (LDH) aged =60 years (NHL-B1) and patients aged 61-75 years (NHL-B2). The data are taken from an interim analysis. Data from 959 patients (CHOP-21: 232; CHOP-14: 238; CHOEP-21: 244; CHOEP-14: 245) from 162 institutions with a total of 5331 therapy cycles were evaluated. RESULTS: The dose adherence in the NHL-B1 trial was excellent. The median relative dose (RD; i.e. actually given compared to planned dose) exceeds 98% for the myelosuppressive drugs in all four regimens. Only =5% of patients received a relative dose <80% (RD <80). The median treatment duration could be shortened as scheduled for both CHOP-14 by 36 days and CHOEP-14 by 35 days. The dose adherence in the NHL-B2 trial was excellent for CHOP-21 and CHOP-14 for the myelosuppressive drugs (median RD >/=98%, RD <80 =15%). Addition of etoposide, however, was accompanied by more dose erosion (median RD >/=97%, RD <80 =17% for CHOEP-21 and =27% for CHOEP-14). The median treatment duration could be shortened by 34 days with CHOP-14 compared with CHOP-21. Less treatment shortening was feasible for CHOEP-14 compared with CHOP-21 (median of 29 days). CHOP-14 and CHOP-21 were similar regarding toxicity profile, rate of infection, use of antibiotics, rate of transfusions and hospitalisation. CHOEP schemes were associated with a higher rate of infections, more transfusion requirements, more antibiotic use and longer hospitalisation than the CHOP schemes, particularly in patients aged >60 years. Haematopoietic recovery was age- and treatment-related. CONCLUSIONS: CHOP-14 with the addition of rhG-CSF is safe and practicable in a large multicentre setting in patients aged 18-75 years. Despite shorter treatment intervals it can be delivered at the same dose as the classical 3-weekly CHOP with a comparable toxicity profile. The addition of etoposide is feasible and safe for patients =60 years old in both the CHOEP-21 and CHOEP-14 schemes. For patients >60 years of age the addition of etoposide is associated with marked dose erosion due to increased toxicity. In this age group CHOEP should be used with caution.