RESUMO
OBJECTIVE: To investigate the clinical characteristics and prognosis of patients with different subtypes of breast cancer: basaloid, HER-2 and luminal types, and try to find the evidence of individualized treatment for the patients. METHODS: 1280 histologically and immunohistochemically proven patients with resectable breast cancer were treated, and the clinical data including characteristics, relapse and survival of the patients with different subtypes of breast cancer were analyzed retrospectively. RESULTS: Of the 1280 breast cancer patients, basaloid, HER-2 and luminal types accounted for 20.9%, 23.2% and 55.9%, respectively. Basaloid type was more likely to be found in younger patients frequently with a family history of breast cancer. HER-2 type usually had a tumor of larger size with more advanced stage disease and more metastatic lymph nodes. Luminal type was likely to occur in aged patients with an earlier stage disease. The recurrence rates in basaloid, HER-2 and luminal types were 25.0%, 27.9% and 11.7%, respectively. Patients with basaloid or HER-2 type were found to have a significantly higher recurrence rate than the patients with luminal type breast cancer (P < 0.001), but no significant difference was observed between the basaloid and HER-2 types. However, patients with basaloid type breast cancer were more likely to develop lung metastasis than HER-2 type (13.4% vs. 7.1%, P = 0.017). Up to December 2006, the 5-year disease-free survival (DFS) rates for patients with basaloid, HER-2 and luminal types were 72.2%, 68.2% and 86.2% (P < 0.001), respectively. The overall 5-yr survival (OS) rates of the three groups were 88.6%, 83.8% and 95.8% (P < 0.001) , respectively. Of the patients with luminal type breast cancer, HER2-negative patients had a higher DFS (86.2% vs 57.0%, P < 0.001) and OS (95.8% vs 87.7%, P = 0.0001) compared with those with HER2-positive. The results of Multivariate Cox Regression showed that tumor size and lymph node state were the most important factors influencing the prognosis. CONCLUSION: Each subtype of breast cancer has somewhat its own specific clinical features in terms of recurrence pattern and prognosis, therefore, individualized treatment regimen may be required.
Assuntos
Neoplasias da Mama/classificação , Neoplasias da Mama/metabolismo , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Adulto , Idoso , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/secundário , Metástase Linfática , Mastectomia/métodos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Radioterapia Adjuvante , Estudos Retrospectivos , Taxa de Sobrevida , Adulto JovemRESUMO
OBJECTIVE: This study was designed to evaluate the efficacy and toxicity of modified BFM-90 regimen originated from Germany authors in the treatment of Chinese childhood and adolescent lymphoblastic lymphoma. METHODS: Thirty-six untreated lymphoblastic lymphoma patients aged from 3 to 18 years were included, with 1 patient in stage II , 9 in stage III and 26 in stage IV. Of these 36 patients, 28 (77.7%) were diagnosed as T cell phenotype, 26 (72. 2%) were found to have mediastinal mass, 21 (58. 3%) had bone marrow involvement. All patients received chemotherapy of modified BFM-90 regimen consisting of induction remission, central nerve system prophylaxis, re-induction remission and maintenance therapy. Total treatment duration was two years. The difference from standard BFM-90 is that we omitted cranial radiotherapy but gave regular high dose methotrexate (MTX) iv infusion and intrathecal MTX therapy during maintenance therapy period. Kaplan-Meier method was used to evaluate survival rate. RESULTS: Of 36 patients, 32 (88%) achieved complete remission (CR) , 1 (2. 7%) partial remission (PR) with an overall response rate of 90.7%. One patient had disease progression ( DP). Two patients received autologous stem cell transplantation at CR1, and two patients received radiotherapy to mediastinum. Totally, 5 patients relapsed, while 2 of them were still alive after salvage chemotherapy. The other 3 died of tumor progression. Two patients died during induction remission, 1 of fungal septicemia, the other of cerebral hemorrhage; one PR and one DP patient died of disease, therefore, totally 7 patients died at last. Median follow-up time was 28 months. Overall three-year survival rate was 78. 3%. The major toxicity was myelosuppression. CONCLUSION: Modified BFM-90 protocol can improve the efficacy and survival of Chinese childhood and adolescent lymphoblastic lymphoma with tolerable toxicity. However, this modified protocol should only be used in experienced cancer center or hematological unit.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Povo Asiático , Asparaginase/uso terapêutico , Criança , Pré-Escolar , China , Ciclofosfamida/uso terapêutico , Citarabina/uso terapêutico , Daunorrubicina/uso terapêutico , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Mercaptopurina/uso terapêutico , Metotrexato/uso terapêutico , Recidiva Local de Neoplasia , Leucemia-Linfoma Linfoblástico de Células Precursoras/etnologia , Prednisona/uso terapêutico , Indução de Remissão , Resultado do Tratamento , Vincristina/uso terapêuticoRESUMO
In this study, we have demonstrated gemcitabine (GEM)-conjugated amphiphilic biodegradable polymeric drug carriers. Our aim was to increase the chemotherapeutic potential of GEM in colon cancer by forming a unique polymer-drug conjugates. The polymer-drug conjugate micelles were nanosized with a typical spherical shape. The GEM-conjugated methoxy poly(ethylene glycol)-poly(lactic acid) (GEM-PL) exhibited a controlled release of drug in both the pH conditions. The developed GEM-PL efficiently killed the HT29 cancers cells in a typical time dependent manner. The clonogenic assay further confirmed the superior anticancer effect of GEM-PL which showed least number of colonies. GEM-PL formulation exhibited a significantly higher apoptosis of cancer cells (â¼25%) when stained using Annexin-V/PI kit. Conjugation of GEM to the mPEG-PLA significantly enhanced the blood circulation potential in animal model compared to that of free GEM. GEM-PL could prevent quick elimination of the drug and can provide sufficient time for the greater accumulation of GEM at the tumor sites. GEM-PL showed a remarkable tumor regression effect as evident from the lowest tumor volume in HT-29 containing tumor model. Overall, mPEG-PLA/GEM conjugates showed the potential of polymer-based drug targeting and might hold significant clinical potential in the treatment of colon cancers.
Assuntos
Antimetabólitos Antineoplásicos , Desoxicitidina/análogos & derivados , Portadores de Fármacos , Animais , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/química , Antimetabólitos Antineoplásicos/farmacocinética , Antimetabólitos Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/uso terapêutico , Desoxicitidina/administração & dosagem , Desoxicitidina/química , Desoxicitidina/farmacocinética , Desoxicitidina/uso terapêutico , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/uso terapêutico , Liberação Controlada de Fármacos , Células HT29 , Humanos , Camundongos Nus , Micelas , Poliésteres/administração & dosagem , Poliésteres/química , Poliésteres/farmacocinética , Poliésteres/uso terapêutico , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/química , Polietilenoglicóis/farmacocinética , Polietilenoglicóis/uso terapêutico , Ratos , Carga Tumoral/efeitos dos fármacos , GencitabinaRESUMO
The mechanisms underlying drug resistance in colorectal cancer (CRC) treatment remain to be fully elucidated. Therefore, the present study aimed to investigate the underlying mechanism resistance to a widely used anticancer drug, 5-Fluorouracil (5-FU). Nuclear factor-erythroid 2-related factor 2 (Nrf2) is an important transcription factor involved in cellular protection. In the present study, it was hypothesized that the epigenetic modification of Nrf2 may be a potential target for 5-FU resistance in CRC treatment. Protein and messenger RNA levels of Nrf2, heme oxygenase-1 (HO-1), DNA methylases and DNA methyltransferases were determined and DNA methylation analysis for the Nrf2 promoter was performed in a human CRC control (SNU-C5) and resistant (SNU-C5R) cell line. The results demonstrated that Nrf2 expression levels, nuclear translocation and promoter binding were significantly increased in SNU-C5R cells compared with SNU-C5 cells. Elevated levels of activated Nrf2 in SNU-C5R cells resulted in the increased protein expression and activity of HO-1. In addition, increased production of reactive oxygen species (ROS) and upregulation of ten-eleven translocation (TET)1 were observed in SNU-C5R cells compared with SNU-C5 cells. Furthermore, methylation analysis revealed Nrf2 promoter cytosine-phosphate-guanine island hypomethylation in 5-FU-treated cells. In conclusion, the results indicated that 5-FU-induced ROS production resulted in the upregulation of TET1 expression and function. In addition, these results indicated that TET-dependent demethylation of the Nrf2 promoter upregulated Nrf2 and HO-1 expression, which induced cellular protection mechanisms, ultimately leading to drug resistance.
RESUMO
BACKGROUND & OBJECTIVE: Few treatment options are available for metastatic breast cancer with resistance to both anthracycline-and taxane-based chemotherapy regimens. Docetaxel combined capecitabine (DC regimen) is approved as a new active regimen for metastatic breast cancer. This study was to explore the efficacy of DC regimen on metastatic breast cancer, and evaluate its safety. METHODS: A total of 31 metastatic breast cancer patients received DC regimen during each 3-week chemotherapy cycle. All patients received oral administration of capecitabine (1250 mg/m(2)) twice daily, within 30 min after meal on day 1 to Day 14, and infusion of docetaxel (75 mg/m(2)) on the first day of each 3-week cycle. All patients received prophylactic therapy with oral dexamethasone (8 mg) twice daily on 3 successive days. RESULTS: A total of 116 cycles of DC regimen were administered, with a median of 3.7 cycles. The objective response rate was 41.9%, with a complete remission (CR) rate of 9.6%. The most frequent treatment-related adverse events were fatigue, leukopenia, nausea, vomiting, hand-foot syndrome, and stomatitis. The median follow-up was 10.8 months (range 2-23 months). Two patients were died of tumor progression. CONCLUSION: The combination of docetaxel and capecitabine provides a well-tolerated and active chemotherapy regimen for metastatic breast cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Desoxicitidina/análogos & derivados , Fluoruracila/análogos & derivados , Taxoides/administração & dosagem , Administração Oral , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Neoplasias da Mama/patologia , Capecitabina , Carcinoma Ductal de Mama/patologia , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Intervalo Livre de Doença , Docetaxel , Fadiga/induzido quimicamente , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Seguimentos , Humanos , Infusões Intravenosas , Leucopenia/induzido quimicamente , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Metástase Linfática , Pessoa de Meia-Idade , Indução de Remissão , Taxoides/efeitos adversosRESUMO
BACKGROUND & OBJECTIVE: Anemia is a common complication of cancer patients. Recombinant human erythropoietin (rhEPO) can alleviate the symptoms of cancer-related anemia. However, the optimal use of rhEPO is still on investigation. This study was to find out the optimal use of rhEPO in anemic cancer patients undergoing chemotherapy. METHODS: From May, 2004 to Feb, 2005, 30 patients with cancer-related anemia receiving concurrent chemotherapy were enrolled. This open-labeled, non-randomized, and pilot study evaluated the response rate of induction rhEPO 120,000 U (40,000 U was subcutaneously injected on d1, 3, 5) followed by subcutaneous injection of maintenance dose of 40,000 U once a week for 3 weeks (d8, 15, 22). Hemoglobin (Hb) and hematocrit (Hct) were measured before treatment and fortnightly during the treatment. RESULTS: Mean Hb maintained increasing during treatment. In week 2 (n=29) and week 4 (n=21), there were 27.59% and 61.90% patients, respectively, whose Hb value had increased more than 20 g/L from the baseline (79.56 g/L) and mean Hb were 90.26 g/L and 96.81 g/L respectively (P<0.05). And mean Hct at week 2 and week 4 were 27.01% and 30.17% respectively, which were higher than the baseline (24.29%)(P=0.062 and 0.001 respectively). All patients demonstrated fine tolerance. CONCLUSION: Induction therapy followed by maintenance with rhEPO can improve the level of hemoglobin significantly and quickly in anemic cancer patients.
Assuntos
Anemia/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Eritropoetina/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Anemia/induzido quimicamente , Neoplasias da Mama/tratamento farmacológico , Feminino , Hematócrito , Hemoglobinas/metabolismo , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Proteínas RecombinantesRESUMO
BACKGROUND & OBJECTIVE: The majority of small cell carcinoma occurs in the lung. Extrapulmonary small cell carcinoma (ESCC) has been recognized as a clinicopathologic entity distinct from small cell carcinoma of the lung. The study was to investigate the clinical characteristics, therapy, and prognosis of ESCC. METHODS: The medical records, from Jan. 1985 to Dec. 2005, of 53 patients with pathologically proved ESCC were analyzed retrospectively. RESULTS: Of the 53 patients, 39 were men and 14 were women, with the median age of 53 years (range, 27-76 years). Of the 53 cases of ESCC, 33 (62.3%) were detected in the esophagus, 5 in the cervix, 4 in the larynx, 3 in the pharynx, 2 in the upper sinus, 2 in the rectum and sublingual gland, 1 in the thyroid gland, 1 in the pleura, and 1 in the liver. Forty patients (75.5%) had limited disease (LD) and 13 (24.5%) had extensive disease (ED). Patients with ED mostly received platinum-based chemotherapy, for which the response rate was 69.2%. Patients with LD were treated with a variety of therapeutic modalities: 7 were treated with surgery plus radiochemotherapy, 3 with surgery plus radiotherapy, 18 with surgery plus chemotherapy, 6 with radiotherapy plus chemotherapy, 4 with radiotherapy alone, and 2 with chemotherapy alone. The median survival time (MST) was 20 months for all patients, and the 1-and 3-year survival rates were 41.3% and 31.4%. MST for patients with ED and LD were 15 months and 26 months, respectively, and 1-and 3-year survival rates were 51.1% vs. 14.4%, and 42.5% vs. 0% (P=0.017 ). CONCLUSIONS: ESCC is identified in various sites, with the most common primary site being the esophagus. Multimodality therapy has become increasingly used for the majority of patients with LD-ESCC. Combination chemotherapy has been a major treatment for patients with ED-ESCC. Generally, the prognosis of LD-ESCC is significantly superior to ED-ESCC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Pequenas , Neoplasias Esofágicas , Radioterapia de Alta Energia , Adulto , Idoso , Carcinoma de Células Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/radioterapia , Carcinoma de Células Pequenas/cirurgia , Radioisótopos de Cobalto , Terapia Combinada , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/radioterapia , Neoplasias Esofágicas/cirurgia , Feminino , Seguimentos , Humanos , Neoplasias Laríngeas/tratamento farmacológico , Neoplasias Laríngeas/radioterapia , Neoplasias Laríngeas/cirurgia , Masculino , Pessoa de Meia-Idade , Aceleradores de Partículas , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/radioterapia , Neoplasias do Colo do Útero/cirurgiaRESUMO
BACKGROUND & OBJECTIVE: Toxicities and their severities vary among advanced gastric cancer patients when they receive the same regimen containing continuous infusion of 5-fluorouracil (5-FU). Dihydropyrimidine dehydrogenase (DPD) is the key rate-limiting enzymes which is closely related to toxicities of 5-FU in chemotherapy. This study was to explore the relationship between activity of DPD and concentration of 5-FU, and their correlation to adverse events among advanced gastric cancer patients treated with the same regimen containing 5-FU continuous infusion. METHODS: Patients received the same regimen (intravenous injection of paclitaxel 75 mg/m(2), leucovorin 200 mg/m(2) and 5-FU 375 mg/m(2), continuous infusion of 5-FU 2.5 g/m2 for 46 hours every two weeks). The peripheral blood was collected from 36 patients with advanced gastric cancer before and after chemotherapy to detect the activity of DPD and concentration of 5-FU by high-performance liquid chromatography (HPLC). Adverse events were assessed every cycle. RESULTS: Serum activity of DPD revealed a unimodel distribution, which globally fits to a guassian distribution (range 1.56-6.01). Mean and median DPD activity values were 2.38 and 2.13, respectively. No total DPD deficiency was found in the patients. The concentration of 5-FU varied from 179.2 microg/L to 1 589.2 microg/L, which demonstrated normality distribution after a logarithmic transformation was applied. The DPD activity was inversely correlated with 5-FU concentration (r=-0.376, P=0.024). The patients with low activity of DPD were more frequently suffering from severe diarrhea, mucositis, and myelosuppression. And high level of 5-FU concentration led to the increase of adverse events. CONCLUSION: Pre-chemotherapy DPD activity and 5-FU concentration during chemotherapy vary among gastric cancer patients, which may help to prevent severe toxicities during the treatment.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Di-Hidrouracila Desidrogenase (NADP)/sangue , Fluoruracila/sangue , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Diarreia/induzido quimicamente , Feminino , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Mucosite/induzido quimicamente , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Neoplasias Gástricas/sangue , Neoplasias Gástricas/patologia , Adulto JovemRESUMO
BACKGROUND & OBJECTIVE: Toxicities and response are different when patients with advanced colorectal cancer were treated with standard FOLFOX6 regimen. Serum level of dihydropyrimidine dehydrogenase (DPD) relates to efficacy and toxicities of chemotherapy containing 5-fluorouracil (5-FU). This study was to explore relationship of DPD to serum concentration of 5-FU in colorectal cancer patients treated with FOLFOX6 regimen, and their correlation to treatment response and adverse events. METHODS: Serum level of DPD in 72 patients with colorectal cancer was detected by high-performance liquid chromatography (HPLC) before chemotherapy. Serum concentration of 5-FU at steady state was detected by HPLC after patients received FOLFOX6 regimen. Treatment response and adverse events in the patients were assessed. RESULTS: Serum levels of DPD were normally distributed in 72 patients (ranged 1.55-5.94), while serum concentrations of 5-FU at steady state were not (ranged 141.1-1 741.9 microg/L). Serum level of DPD was negatively correlated with serum concentration of 5-FU (r=-0.460, P < 0.01). Occurrence of adverse events was lower when 5-FU concentration was less than 600 microg/L than when 5-FU concentration was more than 600 microg/L (P < 0.05). The mean serum concentration of 5-FU was significantly higher in patients with complete response and partial response than in patients with steady disease, and progressive disease (513.9 microg/L vs. 409.8 microg/L, and 259.3 microg/L, P < 0.05). Serum level of DPD was lower in patients suffered oral mucositis and diarrhea of grade II-IV than in patients suffered oral mucositis and diarrhea of grade 0-I (P=0.016, P=0.047). Serum level of DPD had no relation with treatment response of the patients (r=0.312, P=0.078). CONCLUSIONS: DPD level and serum 5-FU concentration vary a lot among patients with colorectal cancer. DPD level negatively correlates with serum 5-FU concentration. Serum concentration of 5-FU correlates with treatment effect and toxicities.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Di-Hidrouracila Desidrogenase (NADP)/sangue , Fluoruracila/efeitos adversos , Neoplasias Retais/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Colo/sangue , Neoplasias do Colo/enzimologia , Diarreia/induzido quimicamente , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/sangue , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Mucosite/induzido quimicamente , Náusea/induzido quimicamente , Compostos Organoplatínicos/administração & dosagem , Neoplasias Retais/sangue , Neoplasias Retais/enzimologiaRESUMO
BACKGROUND & OBJECTIVE: In most instances, advanced non-small cell lung cancer (NSCLC) is treated with primary chemotherapy. Many chemotherapy regimens can palliate cancer-related symptoms and modestly improve survival and quality of life. This clinical trial was designed to compare the efficacy and toxicity of two regimens: PG regimen [cisplatin and gemcitabine] versus PN regimen [cisplatin and vinorelbine]. METHODS: A total of 64 patients were enrolled in this study, 31 patients received PG regimen and 33 patients received PN regimen. Patients in both groups were well-matched with baseline disease characteristics (P >0.05). RESULTS: In PG group, the response rate was 32.3% [10/31, 95% confidence interval (CI):16.3%-48.7%][1 complete response (CR), 9 partial response (PR), 17 no change (NC), 4 progressive disease (PD)]; whereas in group PN, the response rate was 29.03% (9/31,95% CI:13.1%-44.9%) (0CR, 9PR, 17NC, 5PD). The difference of response rates between two groups was not statistically significant (P=0.526, Chi-square test). The median survival were 12 months for group PG (95%CI:10-14 months) and 11 months for group PN (95% CI:10-12 months). The difference of median survival between two groups was not statistically significant(P=0.5799, log-rang test). The major toxicity was myelosuppression. Leucopenia was more pronounced in group PN (P=0.009), Thrombocytopenia was more pronounced in group PG(P=0.01). CONCLUSION: PG and PN are two effective regimens for the patients with advanced NSCLC; the major toxicity was myelosuppression. Leucopenia was pronounced in group PN. Thrombocytopenia was pronounced in group PG. Neurotoxicity was observed in group PN.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Desoxicitidina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Vimblastina/análogos & derivados , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Resultado do Tratamento , Vimblastina/administração & dosagem , Vinorelbina , GencitabinaRESUMO
BACKGROUND AND OBJECTIVE: DDP + 5-Fu and DDP + 5-FU/CF is the standard regimen for the treatment of the patients with recurrent and metastatic nasopharyngeal carcinoma at the present time. The response rate and complete response(CR) rate are still low with short duration of response. More effective regimen was needed. This clinical trial was designed to evaluate the efficacy and toxicity of ifosfamide(IFO) and doxorubicin(ADM) regimen for treatment of the patients with recurrent and metastatic nasopharyngeal carcinoma (NPC) after radiotherapy. METHOD: Ifosfamide was administered intravenously at the dose of 1,200 mg/m2 from day 1 to day 5 with uroprotection of Mesna in fusion at 0, 3, and 6 hours following initiation of IFO. Doxorubicin was given at the dose of 50 mg/m2 intravenously(or Epirubicin 60 mg/m2) at day 1. This combination was repeated every 3 to 4 weeks. RESULTS: Thirty-six patients with recurrent and metastatic NPC following radiotherapy were enrolled, in which 16 patients previously treated by systemic chemotherapy. Thirty-four patients were evaluable for response. The response rate for whole group was 67.6% with CR rate of 14.7%. Median duration of response was 6 months. The response rate of previously patients-treated with and without chemotherapy were 50.0% and 83.3%, respectively, and the median duration of response were 5 months and 8 months, respectively. A total of 109 courses of chemotherapy were administered for 34 patients. The major toxicity was myelosuppression. The incidence of leucopenia was 94.8% with 33.1% of grade 3/4. Febrile leucopenia account for 14.6% and G-CSF was necessary in 24.8% cycles without severe systemic infection and thromocytopenia 8.4%, anemia 11.5%. Meanwhile, other toxicities included loss of appetite, nausea/vomiting, stomatitis, and alopecia were observed. CONCLUSIONS: Ifosfomide and Doxorubicine is an effective regimen for the patients with recurrent and metastatic nasopharyngeal carcinoma. This combination may be considered as salvage therapy for NPC patients who fail to DDP-5-Fu treatment and warranted further clinical study.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Nasofaríngeas/tratamento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Humanos , Ifosfamida/administração & dosagem , Ifosfamida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/radioterapia , Metástase Neoplásica , Prevenção SecundáriaRESUMO
BACKGROUND AND OBJECTIVE: The treatment of the patients with relapsed and refractory non-Hodgkin's lymphoma(NHL) remains difficult. It was reported that DHAP regimen(cisplatin + Ara-C + dexamthsone) was an effective salvage therapy, but there was no report about it in China. The current study was designed to observe the efficacy and toxicity of DHAP regimen for the patients with relapsed and refractory NHL. METHOD: Seventeen patients with relapsed and 10 with refractory intermediate or high grade NHL was involved in this study. These patients were treated with cytarabine 1 g/m2 intravenous(i.v.) every 12 hours on day 1 to 2, cisplatin 20 mg/m2 i.v. on day 1 to 4, dexamethone 40 mg i.v. on day 1 to 4. Four patients with CR after DHAP were followed by autologous peripheral blood stem cell transplantation(APBPCT). RESULTS: Overt responses to DHAP were seen in 12 patients (44.4%) including 8 complete responses(CR) (29.6%) and 4 partial responses (PR) (14.8%). The effective release time lasted a median of 4.8 months. Median survival time was 8.3 months. 1-year and 2-year survival rate were 30.8% and 19.3%, respectively. Myelosuppression was the major toxicity; 15 patients(57.7%) had grade III-IV neutropenia and 21 patients (80.8%) had grade III-IV thromcytopenia, but there was no treatment-related death. CONCLUSION: The authors conclude that DHAP regimen is an effective salvage therapy for the patients with relapsed and refractory NHL, but the remission duration time is short and long-term prognosis remains poor. High dose chemotherapy supported by APBPCT is necessary for improvement in long-term survival.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Criança , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Feminino , Febre/induzido quimicamente , Humanos , Leucopenia/induzido quimicamente , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Recidiva Local de Neoplasia , Taxa de Sobrevida , Resultado do Tratamento , Vômito/induzido quimicamenteRESUMO
BACKGROUND & OBJECTIVE: T-cell lymphoblastic lymphoma in childhood and adolescence is an aggressive malignant disease with higher mortality. BFM-90 regimen for lymphoblastic lymphoma is one of the most effective regimens. This study was designed to evaluate efficacy and toxicities of modified BFM-90 regimen on Chinese children and adolescents with lymphoblastic lymphoma. METHODS: A total of 20 naive children and adolescents with T cell lymphoblastic lymphoma were enrolled, 7 in stage III, and 13 in stage IV. Eighteen (90%) patients suffered from mediastinal mass with superior vena obstruction syndrome,10(50%) suffered from marrow invasion. All patients received modified BFM-90 regimen consisting of induction, consolidation and central nervous system prophylaxis, reinduced alleviation, and maintenance therapy. Total treatment duration was 2 years. Kaplan-Meier method was used to evaluate long-term survival rate. RESULTS: After induction remission,18 patients (90%) achieved complete remission (CR), 1 had partial remission (PR), and 1 had progressive disease (PD), overall response rate was 95%. The 2 patients with PR or PD died of tumor progression. Of 2 patients at CR1 received APBSC, 1 relapsed after transplantation, but achieved CR and survived after salvage chemotherapy;1 survived all along. Of other patients achieved CR, 5 relapsed; of these 5 patients, 1 survived after allogeneic stem cell transplantation, 1 survived after autologous stem cell transplantation, 3 died of progressive disease after chemotherapy. The overall 3-year survival rate was 74%. All patients had myelosuppression of grade III-IV during the induction and reinduction phases, but the hemotologic toxicity was manageable. CONCLUSIONS: Modified BFM-90 regimen is feasible for Chinese children and adolescent patients with lymphoblastic lymphoma, and may improve survival rate of these patients. The major side effect is myelosuppression, but it is manageable.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Asparaginase/uso terapêutico , Criança , Pré-Escolar , Ciclofosfamida/uso terapêutico , Citarabina/uso terapêutico , Daunorrubicina/uso terapêutico , Feminino , Seguimentos , Humanos , Masculino , Mercaptopurina/uso terapêutico , Metotrexato/uso terapêutico , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Prednisona/uso terapêutico , Indução de Remissão , Transplante de Células-Tronco , Taxa de Sobrevida , Resultado do Tratamento , Vincristina/uso terapêuticoRESUMO
BACKGROUND & OBJECTIVE: Hodgkin's disease (HD) is a chemo- and radio-sensitive hematologic malignancy. At present, improvement of cure rate, reduction of long-term toxicity, and maintenance of good quality of life are the major issues in the treatment of HD. The results of long term follow-up from Cancer Center, Sun Yat-sen University were analyzed retrospectively in terms of efficacy and late side effects in this article. METHODS: The results of 295 patients with histology-proven HD from 1970 to 2000, especially from 1980 to 2000 were analyzed. Meanwhile, multivariant analysis (COX model) was employed to determine the prognostic factor. RESULTS: A total of 295 HD patients were treated by chemotherapy-predominant comprehensive modality. The 5, 10, and 20 years overall survival for 295 HD patients were 63.5%, 55.8%, and 47.1%, respectively, with median survival time of 172.3 months (28-351.9 months) at the median follow-up time of 42.9 months (17-351.9 months). The 5, 10, and 20 years overall survival and disease-free survival were 79.6%, 74.5%, and 66.8% as well as 74.5%, 69.4%, and 69.4% respectively for the patients treated with regular chemotherapy and radiotherapy from 1980 to 2000. The incidence rate of late toxicities was low. Multivariate analysis demonstrated that age over 45-year-old, B symptoms and stage III/IV were the main prognostic factors (P = 0.000, P = 0.035, and P = 0.047) in this clinical study. The prognosis of the patients with stage I/II and nodular sclerosis was better in comparison to stages III/IV and other histologic subtypes. CONCLUSIONS: Chemotherapy-predominant combined with involved fields irradiation play an important role in HD treatment with promising long term survival and lower late toxicities. Further investigation for this simplified and convenient comprehensive modality is warranted.
Assuntos
Doença de Hodgkin/mortalidade , Adolescente , Adulto , Idoso , Criança , Ensaios Clínicos como Assunto , Terapia Combinada , Tratamento Farmacológico , Feminino , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/radioterapia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND & OBJECTIVE: In the management of relapsed or refractory non-Hodgkin's lymphoma(NHL), there is still no standard salvage chemotherapy regimen so far. Potentiation of effectiveness and reduction of toxicity for some anti-cancer agents through continuous intravenous infusion were shown in some pre-clinical and clinical studies. The purpose of this study was to evaluate the efficacy and toxicity of EPOCH regimen. METHODS: A prospective phase II study of EPOCH regimen (doxorubicin/epirubicin,vincristine,etoposide over 96 hours infusion with bolus cyclophosphamade and oral prednisone) was administered to 26 patients with relapsed or refractory/resistant aggressive NHL. There were 20 patients (84.7%) among them treated by over 2 kinds of chemotherapy regimen with median regimen types of 2 (range,1-6 types) and median chemotherapy cycles of 8 (range,3-16 cycles) given for all patients. Fifteen patients (65.7%) were chemo-resistant recurrence. RESULTS: All the 26 patients were assessable. The response rate for the whole group was 50.0% with complete remission (CR) rate of 19.2%. Among the 7 patients with T-cell lymphoma and the 19 patients with B-cell lymphoma, the response rates were 28.6% and 57.9%,respectively. Major toxicity was myelosuppression with 34.8% and 8.7%incidence of grade III-IV neutropenia and thrombocytopenia respectively in all 46 cycles of EPOCH. Other toxicities were mild. CONCLUSION: EPOCH was effective for the patients with relapsed or refractory/resistant aggressive non-Hodgkin's lymphoma. Continuous infusion schedules of several chemotherapeutic agents may partially reverse chemo-resistance and reduce toxicity. EPOCH can be used as standard salvage regimen. Further clinical study is warranted.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Etoposídeo/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Prednisona/uso terapêutico , Vincristina/uso terapêutico , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Recidiva , Terapia de Salvação , Resultado do Tratamento , Vincristina/administração & dosagem , Vincristina/efeitos adversosRESUMO
BACKGROUND & OBJECTIVE: Phase II clinical trails showed that paclitaxel is effective in treatment of advanced gastric cancer (AGC). The combination of paclitaxel and 5-fluorouracil (5-FU) in the treatment of advanced gastric cancer is effective and safe. This study was designed to evaluate the efficacy and the toxicity of paclitaxel combined with semimonthly 5-FU/Leucovorin for the AGC patients. METHODS: Twenty-five measurable patients with AGC proved pathologically were enrolled into this study. The chemotherapy regimen was comprised of paclitaxel,75 mg/m(2) i.v. in a 3-hour infusion followed by 2-hour infusion of leucovorin 200 mg/m(2), then 10-minute intravenous bolus of 5-FU 375 mg/m(2), then 48-hour infusion of 5-FU 2.8 g/m(2) using an ambulatory pump. The regimen was given per 14 days. One cycle consisted of twice chemotherapy regimens. All enrolled patients received at least two cycles of treatment. RESULTS: After two cycles of chemotherapy, the complete remission and the partial remission were 8% and 60%, respectively. The median duration of response was 4 months. No treatment-related death occurred. Phlebitis,feeling disorder, and alopecia were main side effects. CONCLUSION: Semimonthly 5-FU/LV combined with paclitaxel has high release rate but comparatively mild toxicity for AGC patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagemRESUMO
BACKGROUND & OBJECTIVES: B cell non-Hodgkin's lymphoma (B-NHL) in childhood and adolescence is aggressive. Routine CHOP regimen can improve the survival rate of patients with early-stage disease, but its effect on patients with advanced disease was poor. Therefore, it is worthwhile to further investigate how to treat patients with B-NHL at different stages. This study was designed to retrospectively analyze and compare CHOP, CHOP+HD-MTX, and BFM-90 regimens in the survival rate of children and adolescents with B-NHL,and explore the optimal therapeutic strategy and protocols. METHODS: Thirty cases of 3- to 17-year-old untreated patients with B-NHL were enrolled in CHOP group, with 13 in Stage I/II, and 17 in stage III/IV (St Jude staging), all patients received standard CHOP for 2 to 8 cycles, the regimen was repeated every 3 weeks. Eighteen cases of 3- to 14-year-old untreated patients with B-NHL were enrolled in CHOP+HD-MTX group, with 6 in Stage I/II, and 12 in stage III/IV (St Jude staging), all patients received CHOP+HD-MTX and intrathecal injection for 2 to 8 cycles, the regimen was repeated every 4 weeks. Twenty-five cases of 1.5- to 15-year-old untreated patients with B-NHL were enrolled in BFM-90 group, with 7 in Stage I/II,and 18 in stage III/IV (St Jude staging). The patients with stage I/II disease received A schema alteration with B schema of BFM-90 regimen for 4 to 6 cycles, while the patients with stage III/IV disease received AA schema alteration with BB schema of BFM-90 regimen for 6 cycles, the interval of cycles was 18-21 days. The survival rates were evaluated by Kaplan-Meier method. RESULTS: In CHOP group,complete response (CR) rate was 70% (21/30), and partial response (PR) rate was 13% (4/30). In CHOP+HD-MTX group, CR rate was 83%, PR rate was 16%. In BFM-90 group, CR rate was 96% (24/25), and PR rate was 4% (1/25). The hematologic toxicity incidence was higher in BFM-90 group than in the other 2 groups. In CHOP group, the overall 2-year survival rate was 52.79% (72.73% for Stage I/II, and 37.82% for stage III/IV). In CHOP+HD-MTX group, the overall 2-year survival rate was 55.56 % (83.33 % for Stage I/II, and 41.67 % for stage III/IV). There was no significant difference between CHOP group and CHOP+HD-MTX group in survival rate (P=0.78). In BFM-90 group,2-year event-free survival rate (EFS) was 84.01 % (100% for Stage I/II, and 77.04 % for stage III/IV). The differences in survival rate between BFM-90 group and CHOP group, CHOP+HD-MTX group were both significant (P=0.013, and P=0.034). CONCLUSION: BFM-90 regimen can greatly improve the survival rate of children and adolescents with B-NHL, especially of patients with advanced NHL. CHOP, and CHOP+HD-MTX regimens work better for the early stage patients, but produce low survival rate for patients with advanced NHL. A high intensive chemotherapy like BFM-90 regimen is necessary for children and adolescents with advanced B-NHL.