RESUMO
BACKGROUND: To evaluate efficacy in patients with brain metastasis (BM) on entry into the lapatinib expanded access program (LEAP). METHODS: LEAP is a worldwide, single-arm, open-label study. HER2-positive, locally-advanced or metastatic breast cancer patients with progression after an anthracycline, taxane, and trastuzumab were eligible. Patients received capecitabine 2000 mg/m(2) daily in two divided doses, days 1-14, every 21 days and lapatinib 1250 mg once daily. RESULTS: Among 186 patients enrolled in 6 Korean centers, 58 had BM. Progression-free survival (PFS) was 18.7 weeks in patients with BM and 19.4 weeks without BM (P = 0.88). In patients with BM, brain response was synchronized with systemic responses (P = 0.0001). Overall survival (OS) was 48.9 weeks in patients with BM and 64.6 weeks without BM (P = 0.23). Multivariable analysis found hormone receptor positivity (P = 0.003) and clinical benefit rate (CBR) of combined systemic and brain disease (P < 0.0001) significantly associated with prolonged brain PFS, and CBR of combined systemic and brain disease (P = 0.03) and longer trastuzumab use (P = 0.047) associated with prolonged OS in patients with BM; prior capecitabine did not affect PFS or OS in patients with BM. CONCLUSION: Lapatinib plus capecitabine is equally effective in patients with or without BM. TRIAL REGISTRATION: ClinicalTrials.gov (NCT00338247).
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/secundário , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Receptor ErbB-2/metabolismo , Adulto , Idoso , Neoplasias Encefálicas/mortalidade , Capecitabina , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/análogos & derivados , Humanos , Lapatinib , Pessoa de Meia-Idade , Quinazolinas/administração & dosagem , Análise de Sobrevida , Resultado do TratamentoRESUMO
A phase II study was performed to evaluate the clinical efficacy and toxicity of oxaliplatin combined with uracil and tegafur (UFT) in patients with advanced colorectal cancer previously treated with a fluoropyrimidine-based regimen. From January to December 1999, 34 patients were enrolled in this study. Patients received intravenous oxaliplatin 130 mg/m2 on day 1 and daily oral UFT 350 mg/m2 in 3 divided doses for 21 days and repeated every 21 days. Thirty-one of 34 patients were assessable for response and 32 patients for toxicity. Partial response was observed in four patients and stable disease in six patients. The response rate was 12.9% (95% CI, 3.6-29.8%) and median duration of response was 17 weeks. The median overall survival and progression-free survival of all patients were 26 weeks (range, 3-90+ weeks) and 9 weeks (range, 3-56 weeks), respectively. Sensory neuropathy was the most common toxicity, but there was no severe toxicity (>grade II) except for a case of grade III neutropenia. We conclude that oxaliplatin and UFT combination chemotherapy was well tolerated without significant toxicities. The results of this trial will serve as the basis for designing new clinical trials with a different dose or schedule.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Adenocarcinoma/secundário , Adulto , Idoso , Neoplasias Colorretais/patologia , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Análise de Sobrevida , Tegafur/administração & dosagem , Uracila/administração & dosagemAssuntos
Neoplasias da Mama/secundário , Carcinoma Hepatocelular/secundário , Neoplasias Hepáticas/patologia , Adulto , Neoplasias da Mama/sangue , Neoplasias da Mama/diagnóstico , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Neoplasias Hepáticas/sangue , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X , alfa-Fetoproteínas/metabolismoRESUMO
BACKGROUND: Objective tumor response is a common endpoint in daily practice as well as in clinical trials to evaluate the efficacy of anti-cancer agents. Traditionally, the standard World Health Organization (WHO) criteria has been adopted in these contexts. However, the recent development of new classes of anti-cancer agents and progress in imaging technology have required new methodology to evaluate response to treatment. Recently, the Response Evaluation Criteria in Solid Tumors Group (RECIST) proposed new guidelines using unidimensional measurement. Theoretically, the simple sum of the maximum diameters of individual tumors is more linearly related to cell kill than is the sum of the bidimensional products. To validate these new guidelines, we have compared the standard WHO response criteria with the new RECIST guidelines in the same patient population. METHODS: Data from 79 patients enrolled in eight prospective phase II studies at Samsung Medical Center were retrospectively re-analyzed to determine the concordance between the two response criteria. The two response criteria were applied separately, and the results were compared using the kappa statistic to test concordance for overall response rate. RESULTS: The overall response rate according to the WHO criteria was 31.6%. Using the RECIST criteria, nine patients were reclassified and the overall response rate was 30.4%. There was excellent agreement between the unidimensional and bidimensional criteria in 23 of 25 responses (92%). The kappa statistic for concordance for overall response was 0.91. CONCLUSIONS: We conclude that the new RECIST guidelines are comparable to the old response criteria in evaluating response in solid tumors. Moreover, the new guidelines are just as simple and reproducible in the measurement of response in daily practice as they are in clinical trials.
Assuntos
Antineoplásicos/uso terapêutico , Ensaios Clínicos Fase II como Assunto/normas , Guias como Assunto , Neoplasias/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Estudos de Avaliação como Assunto , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Organização Mundial da SaúdeRESUMO
Major ABO incompatibility may be potentially associated with immediate or delayed hemolysis and delayed onset of erythropoiesis in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). To determine if hemolysis can be prevented by the inhibition of graft erythropoiesis, we performed hypertransfusion and assessed red cell transfusion requirement and independence. Between October 1995 and December 2001, 28 consecutive patients receiving major ABO incompatible HSCT at Samsung Medical Center were hypertransfused to maintain their hemoglobin levels at 15 g/dL or more. We retrospectively compared the outcomes of these patients with those of 47 patients at Asan Medical Center whose target hemoglobin levels were 10 g/dL. Reticulocyte engraftment was significantly delayed in hypertransfused group (51 days vs. 23 days; p=.001). There was no significant difference in the total amount of red cells transfused within 90 days post-HSCT (25 units vs. 26 units; p=.631). No significant difference in the time to red cell transfusion independence was observed between the two groups (63 days vs. 56 days; p=.165). In conclusion, we failed to improve red cell transfusion requirement and independence in major ABO incompatible HSCT with hypertransfusion.
Assuntos
Sistema ABO de Grupos Sanguíneos , Transfusão de Sangue , Adolescente , Adulto , Eritrócitos/metabolismo , Eritropoese , Feminino , Hemoglobinas/metabolismo , Hemólise , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Transplante de Células-Tronco , Fatores de Tempo , Transplante Homólogo , Resultado do TratamentoRESUMO
The purpose of this study was to determine the activity and safety of docetaxel plus cisplatin as second-line chemotherapy for advanced gastric cancer. This trial included patients who had failed first-line chemotherapy with a 5-fluorouracil regimen within 1 year before their enrollment. After registration, patients were treated with docetaxel intravenously at a dose of 60 mg/m2 given over 1 hour followed by cisplatin 60 mg/m2 given over 2 hours. The treatment was continued every 3 weeks until disease progression or unacceptable toxicity was detected. Forty-three patients were registered and 41 were assessable for response. Seven partial responses were observed (17.1% of the "evaluable" patients; 95% confidence interval [CI], 0-29) with a median response duration of 3.9 months. Stable disease was documented in 2 cases (4.9%). The median survival was 5.8 months (95% CI, 3.4-8.3), resulting in a 1-year survival rate of 23%. Tolerance was acceptable, with the main toxicity being neutropenia. The authors conclude that second-line chemotherapy with docetaxel plus cisplatin for advanced gastric cancer is feasible with an acceptable toxicity level.