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2.
Ann Oncol ; 25(7): 1346-1355, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24718886

RESUMO

BACKGROUND: The Panitumumab Randomized trial In combination with chemotherapy for Metastatic colorectal cancer to determine Efficacy (PRIME) demonstrated that panitumumab-FOLFOX4 significantly improved progression-free survival (PFS) versus FOLFOX4 as first-line treatment of wild-type (WT) KRAS metastatic colorectal cancer (mCRC), the primary end point of the study. PATIENTS AND METHODS: Patients were randomized 1:1 to panitumumab 6.0 mg/kg every 2 weeks + FOLFOX4 (arm 1) or FOLFOX4 (arm 2). This prespecified final descriptive analysis of efficacy and safety was planned for 30 months after the last patient was enrolled. RESULTS: A total of 1183 patients were randomized. Median PFS for WT KRAS mCRC was 10.0 months [95% confidence interval (CI) 9.3-11.4 months] for arm 1 and 8.6 months (95% CI 7.5-9.5 months) for arm 2; hazard ratio (HR) = 0.80; 95% CI 0.67-0.95; P = 0.01. Median overall survival (OS) for WT KRAS mCRC was 23.9 months (95% CI 20.3-27.7 months) for arm 1 and 19.7 months (95% CI 17.6-22.7 months) for arm 2; HR = 0.88; 95% CI 0.73-1.06; P = 0.17 (68% OS events). An exploratory analysis of updated survival (>80% OS events) was carried out which demonstrated improvement in OS; HR = 0.83; 95% CI 0.70-0.98; P = 0.03 for WT KRAS mCRC. The adverse event profile was consistent with the primary analysis. CONCLUSIONS: In WT KRAS mCRC, PFS was improved, objective response was higher, and there was a trend toward improved OS with panitumumab-FOLFOX4, with significant improvement in OS observed in an updated analysis of survival in patients with WT KRAS mCRC treated with panitumumab + FOLFOX4 versus FOLFOX4 alone (P = 0.03). These data support a positive benefit-risk profile for panitumumab-FOLFOX4 for patients with previously untreated WT KRAS mCRC. KRAS testing is critical to select appropriate patients for treatment with panitumumab.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Genes ras , Humanos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Panitumumabe , Qualidade de Vida
3.
Ann Oncol ; 23(1): 72-77, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21464154

RESUMO

BACKGROUND: This open-label phase III study assessed the addition of Toll-like receptor 9-activating oligodeoxynucleotide PF-3512676 to gemcitabine/cisplatin chemotherapy in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Chemotherapy-naive patients with stage IIIB or IV NSCLC were randomized (1:1) to receive six or fewer 3-week cycles of i.v. gemcitabine (1250 mg/m2 on days 1 and 8) and cisplatin alone (75 mg/m2 on day 1, control arm) or combined with s.c. PF-3512676 0.2 mg/kg on days 8 and 15 of each chemotherapy cycle and weekly thereafter until progression or unacceptable toxicity (experimental arm). No crossover was planned. The primary end point was overall survival (OS). RESULTS: A total of 839 patients were randomized. Baseline demographics were well balanced. Median OS (11.0 versus 10.7 months; P=0.98) and median progression-free survival (PFS) (both 5.1 months) were similar between groups. Grade≥3 hematologic adverse events (AEs), injection-site reactions, and influenza-like symptoms were more frequently reported among patients receiving PF-3512676. At the first-interim analysis, the Data Safety Monitoring Committee recommended study discontinuation. Administration of PF-3512676 was halted based on efficacy futility and increased grade≥3 AEs (experimental arm). CONCLUSIONS: Addition of PF-3512676 to gemcitabine/cisplatin chemotherapy did not improve OS or PFS but did increase toxicity.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Oligodesoxirribonucleotídeos/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Oligodesoxirribonucleotídeos/efeitos adversos , Modelos de Riscos Proporcionais , Gencitabina
4.
Cancer Chemother Pharmacol ; 60(3): 365-73, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17569044

RESUMO

PURPOSE: The aim of this study was to investigate the combination of vinorelbine (VRL) alternating intravenous (i.v.) and oral in combination with docetaxel (DCT) as first-line chemotherapy of patients with metastatic breast cancer. PATIENTS AND METHODS: Tested doses were 60 or 70 mg m(-2) given on day 1 for DCT, 20 to 25 mg m(-2) for i.v. VRL on day 1, 60 mg m(-2) on day 8 or day 15 for oral VRL. Day 1 was administered every 3 weeks. Three to six patients were treated per dose level. RESULTS: The median age of the 30 treated patients was 60 years. Four patients were non evaluable for the maximum tolerated dose (MTD) and were replaced. Reported dose-limiting toxicities were 11 omissions of oral VRL for neutropenia, two cases of febrile neutropenia and two grade 4 neutropenia >or=7 days. Dose levels using DCT doses >60 mg m(-2) and/or i.v. VRL doses >20 mg m(-2) met the criteria for MTD. Most frequent toxicities were febrile neutropenia in seven patients and neutropenic infection in four patients (one fatal). Therefore, the recommended schedule was established at i.v. VRL 20 mg m(-2) with DCT 60 mg m(-2) on day 1 and oral VRL 60 mg m(-2) given on day 15 every 3 weeks. At this recommended schedule, only one of six patients experienced febrile neutropenia. Among 22 patients evaluable for tumour response, 2 complete and 10 partial responses were reported. Pharmacokinetics of combined VRL and DCT demonstrated the absence of mutual interaction. CONCLUSIONS: This phase I study established the recommended doses and schedules of the combination alternating i.v. and oral VRL with DCT, this recommended regimen being further explored in a phase II study.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Neoplasias da Mama/patologia , Adulto , Idoso , Neoplasias da Mama/tratamento farmacológico , Progressão da Doença , Docetaxel , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , França , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Polônia , Taxoides/administração & dosagem , Taxoides/toxicidade , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados , Vimblastina/toxicidade , Vinorelbina
5.
Eur J Gynaecol Oncol ; 25(2): 245-6, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15032294

RESUMO

Uncommon pathologic changes of the uterine cervix are rare but not impossible. Described cases of cervical lymphoma indicate the necessity of great attention and careful diagnosis. A watchful examination, imaging procedures and detailed histopathologic findings are of crucial importance in treatment planning. Each of our three patients underwent different types of treatment. A proper choice of therapeutical methods is based on individual disease and patient performance status features. In our patients, chemotherapy, radiotherapy (brachy- and teletherapy) were considered and applied as the sole method or in combination.


Assuntos
Linfoma/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Braquiterapia , Terapia Combinada , Ciclofosfamida/administração & dosagem , Diagnóstico Diferencial , Doxorrubicina/administração & dosagem , Feminino , Humanos , Linfoma/complicações , Linfoma/patologia , Linfoma/terapia , Prednisona/administração & dosagem , Neoplasias do Colo do Útero/complicações , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/terapia , Hemorragia Uterina/etiologia , Vincristina/administração & dosagem
6.
Blood ; 96(8): 2723-9, 2000 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-11023504

RESUMO

The efficacy and toxicity of cladribine (2-CdA) + prednisone (P) versus chlorambucil (Chl) + P were compared in previously untreated patients with progressive or symptomatic chronic lymphocytic leukemia (CLL) in a randomized, multicenter prospective trial. Eligible patients were assigned to either 2-CdA 0.12 mg/kg per day in 2-hour infusions and P 30 mg/m(2) per day for 5 consecutive days or Chl 12 mg/m(2) per day and P 30 mg/m(2) per day for 7 consecutive days. Three courses were administered at 28-day intervals or longer if myelosuppression developed. The therapy was finished if complete response (CR) was achieved. Of 229 available patients 126 received 2-CdA+P and 103 received Chl+P as a first-line treatment. CR and overall response rates were significantly higher in the patients treated with 2-CdA+P (47% and 87%, respectively) than in the patients treated with Chl+P (12% and 57%, respectively) (P = .001). Progression-free survival was significantly longer in the 2-CdA-treated group (P = .01), but event-free survival was not statistically different. Thirteen percent of patients were refractory to 2-CdA+P and 43% to Chl+P (P = .001). Drug-induced neutropenia was more frequently observed during 2-CdA+P (23%) than Chl+P therapy (11%) (P = .02), but thrombocytopenia occurred with similar frequency in both groups (36% and 27%, respectively). Infections were seen more frequently in the 2-CdA+P-treated group (56%) than in the Chl+P-treated group (40%; P = .02). Death rates have so far been similar in patients treated with 2-CdA (20%) and with Chl (17%). The probability of overall survival calculated from Kaplan-Meier curves at 24 months was also similar for both groups (78% and 82%, respectively). (Blood. 2000;96:2723-2729)


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Clorambucila/administração & dosagem , Clorambucila/efeitos adversos , Cladribina/administração & dosagem , Cladribina/efeitos adversos , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Humanos , Incidência , Infecções/epidemiologia , Infecções/etiologia , Leucemia Linfocítica Crônica de Células B/mortalidade , Tábuas de Vida , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Neutropenia/epidemiologia , Polônia/epidemiologia , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Estudos Prospectivos , Indução de Remissão , Taxa de Sobrevida , Trombocitopenia/induzido quimicamente , Trombocitopenia/epidemiologia , Resultado do Tratamento
7.
Clin Cancer Res ; 6(3): 1150-60, 2000 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10741746

RESUMO

On the basis of a retrospective study of 327 patients with Hodgkin's disease (HD), the prognostic significance of several factors, accepted previously and recently proposed, has been analyzed with regard to response to treatment and the survival time. Multivariate regression analysis strongly decreased the number of potentially prognostic parameters. The only independent, pretreatment factors negatively influenced by either time of survival or response to treatment were the following: age at diagnosis of more than 45 years, advanced (IIIB/IV) clinical stage, poor clinical status according to Karnofsky's scale (score less than 70), presence of systemic symptoms, mixed cellularity/lymphocyte depletion histological type, multisite peripheral nodal localization of the disease, abdominal lymphadenopathy, and large primary tumor mass (bulky disease). Short time to achieve complete remission (during the first four courses of chemotherapy) has proven to be significantly positive predictive factor. Cumulative dose of cytostatics lower than programmed was a significantly negative prognostic factor that correlated with a shorter time of survival. Lack of or a too-low dose of radiotherapy had the same predictive value. High activity of serum lactate dehydrogenase correlated moderately with poor response to the first-line treatment but did not influence the survival time. Other clinical, morphological, and biochemical parameters influenced neither the prognosis nor the response to treatment. Additionally, immunohistochemical examinations for proliferating cell nuclear antigen and the protein products of the p53 and bcl-2 genes were performed on the lymph nodes obtained from the patients with HD. High expression of proliferating cell nuclear antigen, p53, and BCL-2 correlated with poor response to the treatment and/or short time of survival. Statistical analysis has led us to the conclusion that the pretreatment expression of these oncoproteins can be taken into consideration as a new prognostic factor in HD.


Assuntos
Doença de Hodgkin/patologia , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Feminino , Seguimentos , Doença de Hodgkin/metabolismo , Doença de Hodgkin/terapia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Prognóstico , Antígeno Nuclear de Célula em Proliferação/análise , Proteínas Proto-Oncogênicas c-bcl-2/análise , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Proteína Supressora de Tumor p53/análise
8.
Leuk Lymphoma ; 34(1-2): 151-7, 1999 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10350343

RESUMO

The aim of our study was to determine the efficacy and toxicity of 2-chlorodeoxyadenosine (2-CdA) in 2-hour infusions in the treatment of elderly patients with B-cell chronic lymphocytic leukemia (B-CLL). Forty three patients aged 70 years and older received 1 to 6 courses of 2-CdA (median 3) in a dose of 0.12 mg/kg daily for 5 consecutive days. Thirty three of them were untreated and 10 had relapsed or refractory to disease after prior therapy with chlorambucil, COP and CHOP. Complete response (CR) was achieved in 13 (30.2%) and partial response (PR) in 17 (39.6%) patients, giving an overall response rate of 69.8%. The difference in overall response rate between both groups were not statistically significant (69.8% and 50%, respectively). The most frequent side effects of 2-CdA treatment were thrombocytopenia observed in 18 (41.9%) and infections in 7 (16.3%) patients. Drug related neutropenia was observed in 6 (13.9%) and allergic dermatitis in 2 patients. Six (13.9%) patients died, one because of drug related thrombocytopenia resulting in a central nervous system hemorrhage, two because of pneumonia and two of cardiovascular complications. In conclusion, our results suggest that 2-CdA is also effective treatment for elderly patients with CLL. The drug toxicity is acceptable and seems to be similar for that observed in younger patients.


Assuntos
Antineoplásicos/uso terapêutico , Cladribina/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Cladribina/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Masculino , Estudos Retrospectivos
9.
Leukemia ; 13(4): 518-23, 1999 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10214856

RESUMO

The aim of the study was to determine the effectiveness of 2-chlorodeoxyadenosine (2-CdA) administered in 2-h i.v. infusions in the treatment of B cell chronic lymphocytic leukemia (B-CLL) in patients 55 years old and younger. One hundred and thirteen patients received three to 10 courses of 2-CdA administered at a dose of 0.12 mg/kg daily for 5 consecutive days. Sixty-seven patients were previously treated with chlorambucil and prednisone, COP and some of them also with CHOP, and 46 were untreated. Complete remission (CR) was achieved in 21 (18.6%) (19 in untreated and two in previously treated) patients and partial response (PR) in 38 (33.6%) (23 and 15, respectively) giving an overall response rate in 52.2%. The differences in CR and overall response rate between previously treated and untreated patients were statistically significant (P = 0.001). Surface immunophenotyping by flow cytometry using dual-color staining on the peripheral blood and/or bone marrow was performed in 38 patients who responded to 2-CdA therapy. Residual disease had been demonstrated in five out of 17 (29.4%) patients who were in CR and in all 21 investigated PR patients. 2-CdA-induced thrombocytopenia occurred in 24 (35.8%) of previously treated and in 13 (28.3%) previously untreated patients (P = NS). Neutropenia was observed in eight (11.9%) and in five (10.9%) patients, respectively (P = NS). Severe infections, including pneumonia and sepsis, occurred more often in previously treated (44.8%) than untreated patients (26.1%) (P < 0.05). Twenty-seven (23.9%) patients died, 11 because of infections, five because of drug-related thrombocytopenia and hemorrhage, one because of second malignancy and eight because of disease progression. In conclusion, our results indicate that 2-CdA is an effective agent in younger patients with B-CLL, especially used as a first line therapy.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Cladribina/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Adulto , Alopecia/induzido quimicamente , Antimetabólitos Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Cladribina/efeitos adversos , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Toxidermias/etiologia , Resistencia a Medicamentos Antineoplásicos , Feminino , Febre/etiologia , Doenças Hematológicas/induzido quimicamente , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Recidiva , Indução de Remissão , Terapia de Salvação , Resultado do Tratamento , Vincristina/administração & dosagem
10.
Eur J Haematol ; 62(1): 49-56, 1999 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9918312

RESUMO

Between January 1991 and December 1997, 103 patients, 97 with typical hairy cell leukemia (HCL) and 6 with HCL-variant (HCL-V) were treated with 2-chlorodeoxyadenosine (2-CdA) given as 2-h infusion for 5 consecutive d at a daily dose 0.12 mg/kg. To our knowledge this is the largest cohort of HCL patients treated with this type of regimen. Median follow-up amounted to 36 months. Fifty-six of 97 patients with typical HCL were newly diagnosed and 41 were relapsed after previous treatment. Splenectomy as a first-line therapy was performed in 23 patients and 18 remaining patients received prednisone, chlorambucil or interferon-alpha (IFN-alpha) alone or in combinations. Seventy-five (77.3%) patients entered CR and 18 (18.6%) achieved PR, giving an overall response rate of 95.9%. The mean time of first CR duration amounting to 32 months (range 3-72) did not correlate to the number of 2-CdA cycles. 2-CdA was equally effective in treatment of newly diagnosed patients and patients who relapsed after previous therapeutic procedures. Relapse of the disease occurred in 20 of 75 patients who achieved CR after 2-CdA and was usually manifested by very discrete changes in peripheral blood counts (neutropenia and/or relative lymphocytosis). The mean progression-free survival (PFS) time in this group was 37.4 (range 10-66) months. Ten of 20 relapsed patients were retreated with 2-CdA given an identical course to the first one. Seven patients entered second CR lasting 19+ (range 8-47) months and 3 experienced PR. This confirms the previous observations that 2-CdA gives no resistance to leukemic clone. Ten remaining patients have not required retreatment so far and remain in a good clinical and hematological state. The results of HCL-V treatment with 2-CdA were poor. Only 2 patients achieved PR and 4 patients did not respond to this drug. Seven patients (5 with typical HCL and 2 with HCL-V) died, 3 of causes unrelated to the disease. Second neoplasms were noted in 5 patients. 2-CdA-related side effects resulted mainly from myelosuppression and infectious complications. In conclusion we confirm the effectiveness of 2-CdA in inducing CR in patients with typical HCL, but this drug is unable to completely eradicate the leukemic clone which results in the relapse of the disease. The real incidence of the relapse rate may be underestimated unless bone marrow biopsy is performed. The results of our study indicate that a 2-h infusion of 2-CdA in HCL patients is at least as effective as a 24-h infusion but more convenient to the patients, and may be given on an outpatient basis.


Assuntos
Antineoplásicos/uso terapêutico , Cladribina/uso terapêutico , Leucemia de Células Pilosas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/toxicidade , Cladribina/administração & dosagem , Cladribina/toxicidade , Estudos de Coortes , Feminino , Humanos , Leucemia de Células Pilosas/mortalidade , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/secundário , Neutropenia/etiologia , Polônia , Taxa de Sobrevida , Trombocitopenia/etiologia , Fatores de Tempo , Resultado do Tratamento
11.
Mediators Inflamm ; 8(6): 277-86, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10815616

RESUMO

We have investigated the serum concentrations of interleukin-6 (IL-6) and two IL-6 family cytokines-oncostatin M (OSM) and leukemia inhibitory factor (LIF)-in 63 patients with B-cell chronic lymphocytic leukemia (B-CLL) and 17 healthy controls using the enzyme-linked immunosorbent assay (ELISA) method. Simultaneously, we measured the serum levels of the soluble forms of two subunits of the IL-6 receptor complex-ligand binding glycoprotein 80 (sIL-6R) and glycoprotein 130 (sgp130). The cytokines and receptors were evaluated in 25 untreated patients and 38 patients treated with cladribine (2-CdA), as well as in 17 healthy controls. We have correlated the serum levels of these proteins with Rai's clinical stage of the disease, the response to 2-CdA treatment and some hematological parameters. We have also evaluated the correlation of the IL-6 serum level with the concentration of OSM and IL-6 soluble receptors. IL-6 was measurable in 62/63 (98.4%), OSM in 20/25 (80%) of untreated and 14/38 (37.8%) of the treated patients. sIL-6R and sgp130 were detectable in all 63 patients and LIF in none of the CLL patients. IL-6 serum level in untreated patients was not significantly different as compared to its concentration in the control group (P>0.05). However, in the patients treated with 2-CdA the IL-6 level was significantly lower (P<0.02), and the lowest concentration was found in the patients with complete remission (CR; median 1.4pg/ml; P<0.02). The concentration of sIL-6R was significantly higher in untreated (median 61.8 ng/ml) and treated (median 50.1 ng/ml) CLL patients when compared to normal persons (median 41.2 ng/ml; P=0.04; P<0.001, respectively). There was no difference between the sIL-6R levels in the patients with CR and the healthy controls. In non-responders sIL-6R concentration was the highest and similar to its level in the untreated patients. OSM level was higher in the untreated patients (median 1.8pg/ml) than in the normal controls (median 0.0pg/ml; P<0.001) and in the CR patients (median 0.0pg/ml; P<0.03). The serum concentration of sgp130 was similar in the untreated (median 480 pg/ml) and treated (median 470 pg/ml) patients, as well as in the healthy persons (median 420 pg/ml; P>0.05). We have found significant positive correlation between the levels of sIL-6R and the lymphocytes count in CLL patients (p=0.423; P<0.001). In addition, sIL-6R and OSM serum concentrations correlated also with CLL Rai stage. In conclusion, the serum level of IL-6, OSM and sIL-6R, but not LIF and sgp130, are useful indicators of CLL activity.


Assuntos
Cladribina/uso terapêutico , Interleucina-6/sangue , Leucemia Linfocítica Crônica de Células B/sangue , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Receptores de Interleucina-6/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/sangue , Receptor gp130 de Citocina , Feminino , Inibidores do Crescimento/sangue , Humanos , Fator Inibidor de Leucemia , Linfocinas/sangue , Masculino , Glicoproteínas de Membrana/sangue , Pessoa de Meia-Idade , Oncostatina M , Peptídeos/sangue , Indução de Remissão , Solubilidade
12.
Immunol Lett ; 60(2-3): 143-8, 1998 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9557956

RESUMO

In order to examine which cytokine could be used as a marker of the biological effect of thyroid hormones or anti-thyroid antibodies in Graves' disease (GD) patients, we simultaneously evaluated the concentrations of TSH, free thyroid hormones (fT3 and fT4), anti-thyroid antibodies (anti-TPO and anti-TG) and a group of cytokines: interleukin-2 (IL-2), tumour necrosis factor alpha (TNFalpha), interleukin-6 (IL-6) and their soluble receptors (sIL-2R, sTNFalphaR, sIL-6R) as well as interleukin-10 (IL-10) in eight GD females and nine normal controls. We found that serum sIL-2R concentrations of GD patients had only the tendency to be higher versus controls, but strong positive correlations between fT3 and fT4 and sIL-2R in peripheral blood of GD subjects were revealed. We showed that sIL-2R was the best cytokine marker, showing very good correlation with the endocrine status of GD patients.


Assuntos
Citocinas/sangue , Doença de Graves/sangue , Glândula Tireoide/fisiopatologia , Adulto , Idoso , Biomarcadores , Feminino , Doença de Graves/fisiopatologia , Humanos , Interleucina-10/sangue , Interleucina-2/sangue , Interleucina-6/sangue , Pessoa de Meia-Idade , Receptores de Interleucina-2/sangue , Receptores de Interleucina-6/sangue , Fator de Necrose Tumoral alfa/análise
13.
Eur J Haematol ; 59(4): 216-20, 1997 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9338619

RESUMO

Eosinophilia and allergic skin reactions are uncommon events after 2-chlorodoxyadenosine (2-CdA, cladribine) administration. A multicentre retrospective analysis of eosinophilia in 360 patients treated with 2-CdA for lymphoid malignancies has been made. B-cell chronic lymphocytic leukaemia (B-CLL) was diagnosed in 153, hairy cell leukaemia (HCL) in 68, low-grade non-Hodgkin's lymphoma (LGNHL) in 119, high-grade NHL in 2 and Waldenstrom's macroglobulinaemia (WM) in 18 patients. 2-CdA was administered at a dose 0.12 mg/kg/d in 2-h intravenous infusion for 5 consecutive d. The courses were repeated monthly. Patients with HCL received 1 cycle of 2-CdA, with NHL 2-6 (mean 3.5) cycles and with B-CLL 3-6 (mean 5) cycles. Twenty patients (5.5%), including 5 with HCL, 6 with LGNHL, 7 with B-CLL and 2 with WM, developed peripheral blood eosinophilia. The mean values of absolute eosinophil count were 0.78x10(9)/l (0.58-1.06x10(9)/l), 0.71x10(9)/l (0.52-1.3x10(9)/l), 85 (0.56-1.82x10(9)/l) and 0.75 (0.74-0.76x10(9)/l), respectively. Eosinophilia occurred in 13 patients after 1 course, in 4 after 2 courses, and in 5 after > or =3 courses of the therapy. In 17 cases it resolved spontaneously. Allergic skin lesions with pruritus were noticed in 3 patients simultaneously with an increase in eosinophil count. All of them required antihistaminic drugs and/or corticosteroids. One patient with B-CLL experienced repeated episodes of eosinophilia. The highest incidence of 2-CdA-induced eosinophilia was noticed in patients with MW (11.1%) and HCL (7.4%) who received only 1 cycle of this drug and entered a complete remission. This side effect was less frequently observed in LGNHL and B-CLL, i.e. in 5.0% and 4.6% of cases, respectively. The mechanism of 2-CdA-induced eosinophilia is not clear. It has been postulated that massive tumour cell lysis may trigger a release of IL-5 and probably other cytokines. The allergic mechanism of 2-CdA-induced eosinophilia is also possible, especially in patients with simultaneous skin reactions.


Assuntos
2-Cloroadenosina/análogos & derivados , Antimetabólitos Antineoplásicos/efeitos adversos , Desoxiadenosinas/efeitos adversos , Eosinofilia/induzido quimicamente , Transtornos Linfoproliferativos/tratamento farmacológico , 2-Cloroadenosina/administração & dosagem , 2-Cloroadenosina/efeitos adversos , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Desoxiadenosinas/administração & dosagem , Eosinofilia/sangue , Eosinofilia/fisiopatologia , Feminino , Humanos , Infusões Intravenosas , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
14.
Leuk Lymphoma ; 25(3-4): 381-5, 1997 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-9168448

RESUMO

Three patients with B-prolymphocytic variant of HCL (HCL-V) were treated with a chlorinated purine analogue, 2-chlorodeoxyadenosine, at a daily dosage of 0.12 mg/kg in 2-hour intravenous infusion for 5 consecutive days. Partial remission was achieved in only 1 patient, who relapsed after 6 months. Two other patients did not respond to the treatment. HCL-V is a distinct clinicopathological entity which seems to be resistant to various therapeutic modalities. However, further observations are necessary in order to establish the efficacy of 2-CdA in the treatment of HCL-V.


Assuntos
Cladribina/uso terapêutico , Leucemia de Células Pilosas/tratamento farmacológico , Idoso , Antígenos de Superfície/metabolismo , Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Leucemia de Células Pilosas/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva , Indução de Remissão , Baço/patologia , Resultado do Tratamento
15.
Eur J Haematol ; 58(2): 109-13, 1997 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9111592

RESUMO

Autoimmune haemolytic anaemia (AIHA) is one of the major complications in chronic lymphocytic leukaemia (CLL). Treatment with alkylating agents and the adenosine analogue, fludarabine, might trigger the development of AIHA in CLL patients despite the reduction of leukaemic clone. The influence of 2-chlorodeoxyadenosine (2-CdA) on AIHA in patients with CLL is undefined so far. In a group of 114 patients treated at our clinics with this agent, AIHA with direct antiglobulin test (DAT) positively was observed in 25 (21.9%) patients. In 23 patients AIHA was noticed before the starting of 2-CdA and in 2 patients DAT became positive after 2-CdA treatment. In 6 patients the drug caused complete resolution of haemolysis and DAT became negative. Eight patients exhibited partial resolution of haemolysis with significant improvement in haemoglobin level but DAT test remained positive. In 11 patients there was no response to 2-CdA in relation to autoimmune haemolysis. Two patients with no previous history of haemolysis developed AIHA after 5 and 6 courses of 2-CdA therapy and their DAT became positive 1-2 months after the last course of the drug. One of them entered severe haemolytic crisis and severe thrombocytopenia and died because of haemorrhagy to the central nervous system. In the other patient AIHA was controlled by steroids and chlorambucil treatment. Our study indicates that 2-CdA may suppress autoimmunohaemolytic process in some patients with CLL and trigger the development of AIHA in others.


Assuntos
Anemia Hemolítica Autoimune/etiologia , Antineoplásicos/uso terapêutico , Cladribina/uso terapêutico , Leucemia Linfocítica Crônica de Células B/complicações , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Adulto , Idoso , Anemia Hemolítica Autoimune/sangue , Anemia Hemolítica Autoimune/epidemiologia , Antígenos CD/sangue , Linfócitos B/imunologia , Teste de Coombs , Feminino , Hemólise , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
16.
J Med ; 28(3-4): 199-209, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9355024

RESUMO

We present a 68-year old patient with B-cell chronic lymphocytic leukemia (CLL) treated with 2-chlorodeoxyadenosine (2-CdA). This is the first reported patient with B-CLL in whom skin lesions and eosinophilia were observed simultaneously. The most frequent side effect of this drug is myelosuppression with pancytopenia. So far, there have been few reports of cases where either skin reactions or eosinophilia, occurring separately, were observed as side effects from 2-CdA treatment.


Assuntos
Antineoplásicos/efeitos adversos , Cladribina/efeitos adversos , Toxidermias/etiologia , Eosinofilia/induzido quimicamente , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Idoso , Humanos , Masculino
17.
Eur J Cancer ; 33(14): 2347-51, 1997 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9616280

RESUMO

2-Chlorodeoxyadenosine (2-CdA) is a new antimetabolite chemotherapeutic agent active in indolent lymphoid malignancies. In this retrospective study, 69 previously untreated patients with B-cell chronic lymphocytic leukaemia (B-CLL) were treated with 2-CdA administered at a dose of 0.12 mg/kg daily in 2-h intravenous infusion for 5 consecutive days. 45 patients also received prednisone 30 mg/m2 orally each day for 5 days starting with 2-CdA courses. Patients were given 2-6 courses (mean 4.6) of 2-CdA repeated usually at monthly intervals. If a complete response was achieved, no further 2-CdA courses were administered. Guidelines for response were those developed by the NCI Sponsored Working Group. Complete response (CR) was achieved in 26 (38%) and partial response (PR) in 27 (39%) cases, giving an overall response rate of 77%. 16 patients (23%) did not respond to 2-CdA. In the subgroup of 45 patients receiving 2-CdA with prednisone, CR was obtained in 15 (33%) and PR in 20 (44%) patients giving an overall response rate of 78%. CR was achieved in 11 (46%) out of 24 patients treated only with 2-CdA and in 7 cases (29%) PR was observed, giving an objective response rate of 75%. The differences between both subgroups were not statistically significant. However, we observed a relationship between the response and the number of courses of 2-CdA given in patients receiving and those not receiving prednisone. In the subgroup receiving 2-CdA with prednisone, an earlier response to 2-CdA was observed. In this group a response was achieved in 9 (20%) patients after two courses of 2-CdA and in 18 (40%) after four courses. In the subgroup receiving only 2-CdA, 17 (71%) responses were obtained after six cycles.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cladribina/administração & dosagem , Cladribina/efeitos adversos , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Estudos Retrospectivos , Análise de Sobrevida
18.
Leuk Lymphoma ; 22(1-2): 107-11, 1996 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8724536

RESUMO

Forty one patients with hairy cell leukemia (HCL) were treated with 2-chloro-deoxyadenosine (2-CdA) administered in various schedules. Complete remission (CR) was achieved in 31 (76%) patients and partial remission (PR) in 9 (22%). The mean duration of remission (CR + PR) was 25.2 months (range 9-45 months). One patient did not respond to therapy. Twelve out of 16 patients (75%) achieved CR after 5-day intravenous infusions of 2-CdA and 19 out of 25 patients (76%) after 7-day courses. In 19 out of 23 patients (82.6%) CR was achieved after intermittent 2-hour infusions and in 12 out of 18 (66.7%) after continuous 24-hour infusion. The differences were not statistically significant. Side effects of 2-CdA were similar in both groups except for infections, which were less frequently observed in the group treated for 5 days. The results of our study suggest that 2-CdA can be effectively administered to patients with HCL using 5-day courses and a 2-hour daily infusion.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Cladribina/administração & dosagem , Leucemia de Células Pilosas/tratamento farmacológico , Adulto , Idoso , Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/uso terapêutico , Cladribina/efeitos adversos , Cladribina/uso terapêutico , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Infecções/epidemiologia , Infusões Intravenosas , Interferon-alfa/uso terapêutico , Leucemia de Células Pilosas/cirurgia , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Esplenectomia , Resultado do Tratamento
19.
Arch Immunol Ther Exp (Warsz) ; 42(1): 25-9, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-7503629

RESUMO

Six patients with hairy cell leukemia have been treated with 2-chloro-2'-deoxyadenosine in a dose 0.05 mg/kg/daily in 2 h intravenous infusions during 7 consecutive days. Two patients underwent splenectomy with no clinical or hematologic improvement. Complete remission has been achieved in 4 patients and partial remission in one. 2-CdA was not effective in a patient with HCL-variant. The longest unmaintained CR lasted 11 months. The drug was well tolerated. Only slight side effects were observed. The drug exerted, however, myelosuppressive action resulting in cytopenias in the peripheral blood. Clinical consequences of this activity require further investigation. 2-CdA seems to be a drug of choice in the management of HCL.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Cladribina/uso terapêutico , Leucemia de Células Pilosas/tratamento farmacológico , Idoso , Antimetabólitos Antineoplásicos/efeitos adversos , Cladribina/efeitos adversos , Terapia Combinada , Esquema de Medicação , Feminino , Humanos , Infusões Intravenosas , Leucemia de Células Pilosas/cirurgia , Masculino , Pessoa de Meia-Idade , Esplenectomia
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