RESUMEN
BACKGROUD: The R98 trial explores the addition of irinotecan to a 5-fluorouracil (5-FU) plus leucovorin (5-FU/LV) adjuvant regimen in optimally resected stages II-III rectal cancers. We report the updated long-term results. Disease-free survival (DFS) was the primary end point. PATIENST AND METHODS: Between March 1999 and December 2005, 357 patients were randomized: 178 in 5-FU/LV and 179 in LV5-FU2 + irinotecan arm. The trial was stratified by control arm: Mayo Clinic regimen or LV5-FU2 regimen. RESULTS: Three hundred and fifty-seven randomized patients were evaluable for efficacy. With a follow-up of 156 months, the DFS was in favour of experimental arm but did not reach statistical significance [hazard ratio (HR) = 0.80, P = 0.154]. The same was observed for overall survival (OS) (HR = 0.87, P = 0.433). The 5-year DFS was 58% in the control arm and 63% in the experimental arm. The 5-year OS was 74% in the control arm and 75% in the experimental arm. Patients allocated to the experimental arm had more grade 3-4 neutropenia when compared with the LV5-FU2 arm (33% versus 6%, P = 0.03), but not when compared with the Mayo Clinic arm (33% versus 36%, P = 0.84). Grade 3-4 diarrhoea tended to be higher in the experimental arm, but analyses stratified by control arm or by radiotherapy failed to show significant differences across strata (test for interaction P = 0.44). CONCLUSION: Even though a benefit of irinotecan in subgroups of patients cannot be excluded, due to early termination and lack of power, the study does not support the addition of irinotecan to 5-FU/LV in routine in patients with resected stage II-III rectal cancer.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Camptotecina/análogos & derivados , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Camptotecina/efectos adversos , Camptotecina/uso terapéutico , Quimioterapia Adyuvante , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Terminación Anticipada de los Ensayos Clínicos , Femenino , Fluorouracilo/uso terapéutico , Francia , Humanos , Irinotecán , Leucovorina/uso terapéutico , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias del Recto/mortalidad , Neoplasias del Recto/patología , Factores de Riesgo , Análisis de Supervivencia , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Standard adjuvant chemotherapy regimens for patients with node positive (N+) breast cancer consisted of anthracycline followed by taxane. The European Association for Research in Oncology embarked in 2000 on a phase III trial comparing 6 cycles of FEC100 versus 4 FEC100 followed by 4 Taxol. Primary end-point was disease free survival. Secondary end-points were overall survival, local recurrence free interval, metastases free interval and safety. PATIENTS AND METHODS: Between March 2000 and December 2002, 837 patients were randomised between 6FEC100 for 6 cycles (417patients) or FEC100 for 4 cycles then Taxol 175mg/m(2)/3 weeks for 4 cycles (4FEC100-4T) (420 patients). One thousand patients had been planned initially but the trial was closed earlier due to slow accrual. RESULTS: Hazard ratios (HRs) were 0.99 for disease-free survival (DFS) (95%CI: 0.77-1.26; p=0.91), and 0.85 for overall survival (OS) (95%CI: 0.62-1.15; p=0.29). Nine-year DFS were 62.9% versus 62.5% for 6FEC100 and 4FEC100-4T, respectively. Nine-year OS were 73.9% versus 77% for 6FEC100 and 4FEC100-4T, respectively. Toxicity analyses based on 803 evaluable patients showed that overall grade 3-4 toxicities were similar in both arms (63% versus 58% for 6FEC100 arm and 4FEC100-4T arm, respectively; p=0.16). CONCLUSION: In this trial replacing the last 2 FEC100 cycles of 6FEC100 regimen by 4 Taxol does not lead to a discernable DFS or OS advantage. The lack of a significant difference between the randomised treatment arms may however be due to a lack of power of this trial to detect small, yet clinically worthwhile, treatment benefits.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Quimioterapia Adyuvante , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Epirrubicina/administración & dosificación , Epirrubicina/efectos adversos , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Metástasis Linfática , Persona de Mediana Edad , Paclitaxel/administración & dosificación , Resultado del TratamientoRESUMEN
Phyllodes tumors and sarcomas of the breast are non-epithelial tumors of the breast. Phyllodes tumors are benign tumors, tumors of intermediate malignancy or malignant tumors. The differential diagnosis with a very proliferant fibroadenoma may be difficult. Histological sub-type, type of surgery (definitive or not) and stromal proliferation determine the prognosis. There is a risk of local relapse and distant metastases, in particular to the lung. Surgery (often radical) is the standard treatment. Radiotherapy is recommended in case of high-grade tumor and after conservativetreatment. Breast sarcomas are even rarer. All histological types exist with a predominance of histiofibrocytome type tumors. Grade, involved margins and sometimes tumor necrosis are major prognostics factors. Among the various sub-types, angiosarcoma is characterized by a high risk of occurrence in irradiated fields and by a poor prognosis with a high risk of lung metastases. The treatment is mostly based on mastectomy without lymph node dissection given the exceptional flooding axillary. In some situations, a conservative treatment can be discussed, based on tumor size, grade and volume of the breast. Locoregional radiotherapy is often proposed for tumors over 5 cm and/or of high grade. Systemic chemotherapy is not a standard but should be discussed in the forms at high risk of relapse (like angiosarcoma).
Asunto(s)
Neoplasias de la Mama/patología , Tumor Filoide/patología , Sarcoma/patología , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/terapia , Femenino , Hemangiosarcoma/patología , Hemangiosarcoma/secundario , Hemangiosarcoma/terapia , Humanos , Recurrencia Local de Neoplasia , Tumor Filoide/secundario , Tumor Filoide/terapia , Pronóstico , Sarcoma/secundario , Sarcoma/terapiaRESUMEN
The objective of the study was to assess the prescription patterns of fulvestrant in clinical practice in France through a retrospective observational study. Primary endpoint was treatment duration. Data from patients who completed fulvestrant therapy between January and May 2007 were collected between May and June 2007 in 50 centers selected among a representative study sample of 110 centers. Two hundred seventeen patients were included. For 98-99% of patients, baseline characteristics were consistent with the approved indication in terms of postmenopausal status, estrogen-receptor positive tumors and treatment for advanced disease. Overall, 94% of patients had received previous endocrine therapy: tamoxifen in 60% and aromatase-inhibitor (AI) in 90%, including 35% exposed to AI as the unique prior endocrine therapy. Median duration of fulvestrant therapy was six months, and fulvestrant was the ultimate hormone therapy in 89% of evaluable patients. Fulvestrant is prescribed in the real practice in post-menopausal patients with ER-positive tumors, after prior hormone therapy and for advanced disease in the vast majority of patients, according to drug labeling. Due to the growing population receiving AI after or instead of tamoxifen, most patients given fulvestrant in 2007 in France were previously exposed to AI.
Asunto(s)
Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Estradiol/análogos & derivados , Antagonistas de Estrógenos/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Instituciones Oncológicas/estadística & datos numéricos , Esquema de Medicación , Estradiol/uso terapéutico , Femenino , Francia , Fulvestrant , Humanos , Persona de Mediana EdadRESUMEN
BACKGROUND: This study characterizes the histological effect of chemotherapy (CT) on primary colonic tumors. METHODS: Between 2000 and 2006, 38 patients with stage IV colon cancer underwent resection of the primary, after chemotherapy (CT group, n = 16) or without preoperative CT (control group, n = 22). For all primary tumors, histological analysis included: fibrosis, acellular necrosis, acellular mucin pools, lymphoplasmacytic infiltration, and changes at tumor surface. Tumor regression grade (TRG) was determined by the amount of residual tumor cells and was graded from 1 to 5. RESULTS: No patient had complete histological response. Major histological tumor regression (TRG2) was observed in 70% of patients treated by CT and none of the not treated patients (P < 0.0001). Fibrosis, acellular necrosis, and surface changes were significantly increased in the CT group. TRG in the primary was comparable to the TRG in the corresponding liver metastases for 7/9 patients who underwent both colonic and hepatic resection after CT. CONCLUSION: CT induces major histological response in 70% of colon cancers. Response to CT in the primary and the corresponding liver metastases are correlated. These results support a policy of initial CT management for stage IV colon cancer and may warrant future studies of neoadjuvant CT in locally advanced colon carcinomas.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasia Residual/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Quimioterapia Adyuvante , Neoplasias del Colon/cirugía , Femenino , Humanos , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Inducción de Remisión , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
This phase II trial was performed to evaluate the efficacy and tolerability of oral tegafur-uracil (UFT) with leucovorin (LV) combined with intravenous (i.v.) irinotecan every 3 weeks (TEGAFIRI) as first-line treatment for patients with metastatic colorectal cancer (mCRC). Patients received oral UFT 250 mg m(-2) day(-1) and LV 90 mg day(-1) in three divided daily doses for 14 days followed by a 1-week rest and i.v. irinotecan 250 mg m(-2) as a 90-min infusion every 3 weeks. Tumour responses, assessed every two cycles using RECIST criteria, were reviewed by an independent review committee. In 52 evaluable patients, the best overall response rate was 33% (95% confidence intervals (CI) 20-47%; 1 complete and 16 partial responses). The median time to progression was 5.4 months (95% CI 3.02-7.52 months) and median overall survival was 14.9 months (11.73-17.97 months). A total of 307 cycles were administered, with a median number of five cycles per patient (range: 1-10). The most common grade 3/4 toxicities were neutropenia (25% of patients), diarrhoea (22%), vomiting (11%) and anaemia (11%). The TEGAFIRI regimen is a feasible, well-tolerated and convenient treatment option for patients with non-resectable mCRC.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , Neoplasias Colorrectales/patología , Femenino , Humanos , Irinotecán , Leucovorina/administración & dosificación , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Tegafur/administración & dosificación , Resultado del Tratamiento , Uracilo/administración & dosificaciónRESUMEN
BACKGROUND: Adding a taxane to anthracycline-based adjuvant chemotherapy prolongs survival in node-positive patients but optimal dose and schedule remain undetermined. This study aimed to select a dose-dense regimen for further assessment in phase III studies. PATIENTS AND METHODS: Ninety-nine patients with node-positive invasive breast adenocarcinoma were randomly assigned to docetaxel (Taxotere) (T) 75 mg/m2, epirubicin (E) 75 mg/m2 and cyclophosphamide (C) 500 mg/m2 (TEC)x6, every 3 weeks; E 100 mg/m2, C 600 mg/m2 x 4, then T 100 mg/m2 x 4 (EC-->T) or the reverse sequence (T-->EC), every 2 weeks, with pegfilgrastim support. The primary end point was the incidence of grade 4 toxicity. RESULTS: Dose intensity was almost doubled with dose-dense regimens, compared with TEC. Twenty-seven patients experienced grade 4 toxicity: 26%, 40% and 18% with TEC, EC-->T and T-->EC, respectively, mainly neutropenia, but febrile neutropenia occurred only in 11%, 10% and 3%. Grade 3-4 nail disorders, hand-foot syndrome and peripheral neuropathy occurred in 46%, 73% and 68% of patients with TEC, EC-->T and T-->EC, respectively. CONCLUSIONS: Dose-dense regimens yield more frequent and severe nonhematological toxic effects than standard dose TEC regimen. Though grade 4 toxicity rates appear acceptable with the T-->EC regimen, the incidence of grade 3-4 events makes it difficult to recommend either dose-dense regimen for further investigation.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/tratamiento farmacológico , Carcinoma Lobular/tratamiento farmacológico , Ganglios Linfáticos/patología , Adulto , Anciano , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/secundario , Carcinoma Lobular/secundario , Ciclofosfamida/administración & dosificación , Docetaxel , Relación Dosis-Respuesta a Droga , Epirrubicina/administración & dosificación , Estudios de Factibilidad , Femenino , Humanos , Metástasis Linfática , Persona de Mediana Edad , Invasividad Neoplásica/patología , Estadificación de Neoplasias , Pronóstico , Tasa de Supervivencia , Taxoides/administración & dosificación , Resultado del TratamientoRESUMEN
PURPOSE: To provide empirical evidence on the impact of on-site initiation visits on the following outcomes: patient recruitment, quantity and quality of data submitted to the trial coordinating office, and patients' follow-up time. PATIENTS AND METHODS: This methodological study was performed as part of a randomized trial comparing two combination chemotherapies for adjuvant treatment of breast cancer. Centers participating to the trial were randomized to either receive systematic on-site visits (Visited group), or not (Non-visited group). RESULTS: The study was terminated after two years, while the main randomized trial continued. Of the 135 centers that had expressed an interest in the trial, only 69 randomized at least one patient (35/68 in the Visited group, 34/67 in the Non-visited group). Almost two-thirds of the patients were entered by 17 centers (10 in the Visited group, seven in the Non-visited group) that accrued more than 10 patients each. None of the prespecified outcomes favored the group of centers submitted to on-site initiation visits (ie, mean number of queries par patient: 6.1 +/- 9.7 versus 5.4 +/- 6.4, respectively for the Visited and Non-visited groups). Spontaneous transmittal of case report forms, although required by protocol, was low in both randomized groups (mean number of pages per patient: 1.5 +/- 2.0 versus 2.1 +/- 2.3, respectively), with investigators submitting about one-third of the expected forms on time (29% and 39%, respectively). LIMITATIONS: This study could not evaluate the impact of repeated on-site visits on clinical outcomes. CONCLUSION: Systematic on-site initiation visits did not contribute significantly to this clinical trial.
Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Oncología Médica/normas , Evaluación de Resultado en la Atención de Salud , Selección de Paciente , Ensayos Clínicos Controlados Aleatorios como Asunto/normas , Antineoplásicos Fitogénicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia Adyuvante , Ciclofosfamida/uso terapéutico , Epirrubicina/uso terapéutico , Femenino , Fluorouracilo/uso terapéutico , Humanos , Paclitaxel/uso terapéutico , Proyectos de InvestigaciónRESUMEN
In the last 2 decades, major progresses have been made in the management of patients with advanced colorectal cancer (ACC). The modulation of 5-fluorouracil (5-FU) by folinic acid (LV), followed by the introduction of irinotecan and oxaliplatin have significantly improved the outcome of these patients. New strategies consist of oral fluoropyrimidines, and of targeted agents to inhibit cancer signalisation.
Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , HumanosRESUMEN
PURPOSE: The modulation of fluorouracil (FU) by folinic acid (leucovorin [LV]) has been shown to be effective in terms of tumor response rate in patients with advanced colorectal cancer, but a meta-analysis of nine trials previously published by our group failed to demonstrate a statistically significant survival difference between FU and FU-LV. We present an update of the meta-analysis, with a longer follow-up and the inclusion of 10 newer trials. PATIENTS AND METHODS: Analyses are based on individual data from 3,300 patients randomized in 19 trials on an intent-to-treat basis. Two trials had multiple comparisons, leading to a total of 21 pair-wise comparisons. FU doses were similar in both arms in 10 pair-wise comparisons, 15% to 33% higher in the FU-alone arm in six comparisons, and more than 66% higher in five comparisons. RESULTS: Overall analysis showed a two-fold increase in tumor response rates (11% for FU-LV v 21% for FU-LV v 11% for FU [corrected] alone; odds ratio, 0.53; 95% CI, 0.44 to 0.63; P <.0001) and a small but statistically significant overall survival benefit for FU-LV over FU alone (median survival, 11.7 v 10.5 months, respectively; hazards ratio, 0.90; 95% CI, 0.87 to 0.94; P =.004), which were primarily seen in the first year. We observed a significant interaction between treatment benefit and dose of FU, with tumor response and overall survival advantages of FU-LV over FU-alone being restricted to trials in which a similar dose of FU was prescribed in both arms. CONCLUSION: This updated analysis demonstrates, on a large data set, that FU-LV improves both response rate and overall survival compared with FU alone and that this benefit is consistent across various prognostic factors.
Asunto(s)
Antimetabolitos Antineoplásicos/farmacología , Antimetabolitos Antineoplásicos/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Fluorouracilo/farmacología , Fluorouracilo/uso terapéutico , Leucovorina/administración & dosificación , Anciano , Femenino , Humanos , Leucovorina/farmacología , Masculino , Persona de Mediana Edad , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: The purpose of this study was to evaluate the tolerance and efficacy of combining i.v. irinotecan, 5-fluorouracil (5-FU) and leucovorin (LV) with hepatic arterial infusion (HAI) of pirarubicin in non-resectable liver metastases from colorectal cancer. PATIENTS AND METHODS: Thirty-one patients were included in a phase II trial with i.v. irinotecan/5-FU/LV administered every 2 weeks, combined with HAI pirarubicin 60 mg/m(2) on day 1 every 4 weeks. In most cases HAI was administered via a percutaneous catheter. RESULTS: The main grade 3/4 toxicity was neutropenia, encountered in 78% of the patients. When all patients were considered in the analysis, tumour response rate was 15 out of 31 [48%; 95% confidence interval (CI) 32% to 65%]. Liver resection was made possible in 11 patients (35%; 95% CI 21% to 53%). There were no toxic death. Median overall survival was 20.5 months, and median progression-free survival was 9.1 months. In patients with completely resected metastases, median overall survival was not reached and median progression-free survival was 20.2 months. CONCLUSION: The multimodality approach used in the present study was well-tolerated and yielded dramatic responses. An aggressive approach combining i.v. and HAI chemotherapy deserves further investigation.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Camptotecina/análogos & derivados , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Doxorrubicina/análogos & derivados , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Adulto , Anciano , Camptotecina/administración & dosificación , Terapia Combinada , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Esquema de Medicación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Infusiones Intraarteriales , Infusiones Intravenosas , Irinotecán , Leucovorina/administración & dosificación , Masculino , Persona de Mediana Edad , Neutropenia/inducido químicamenteRESUMEN
Knowledge of the function of the cell cycle checkpoints in tumour cells may be important to develop treatment strategies for human cancers. The protein p53 is an important factor that regulates cell cycle progression and apoptosis in response to drugs. In human malignant mesothelioma, p53 is generally not mutated, but may be inactivated by SV40 early region T antigen (SV40 Tag). However, the function of p53 has not been investigated in mesothelioma cells. Here, we investigated the function of the cell cycle checkpoints in six human mesothelioma cell lines (HMCLs) by studying the cell distribution in the different phases of the cell cycle by flow cytometry, and expression of cell cycle proteins, p53, p21(WAF1/CIP1) and p27(KIP1). In addition, we studied p53 gene mutations and expression of SV40 Tag. After exposure to gamma-radiation, HMCLs were arrested either in one or both phases of the cell cycle, demonstrating a heterogeneity in cell cycle control. G1 arrest was p21(WAF1/CIP1)- and p53-dependent. Lack of arrest in G1 was not related to p53 mutation or binding to SV40 Tag, except in one HMCL presenting a missense mutation at codon 248. These results may help us to understand mesothelioma and develop new treatments.
Asunto(s)
Ciclo Celular/efectos de la radiación , Rayos gamma , Genes cdc/efectos de la radiación , Mesotelioma/patología , Inhibidor p21 de las Quinasas Dependientes de la Ciclina , Ciclinas/genética , Ciclinas/metabolismo , Humanos , Mutación , Virus 40 de los Simios/genética , Células Tumorales Cultivadas , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
Biomodulated 5-fluorouracil-based therapy is the mainstay of treatment for advanced colorectal cancer. Patients with advanced disease do better with chemotherapy than they do without, but the overall survival in these patients is still poor. Combination of infusional and bolus 5-fluorouracil/folinic acid (leucovorin) regimens with newer agents, such as CPT-11 and oxaliplatin, in the fist-line treatment of patients with advanced colorectal cancer, has yielded increased response rates and progression-free survivals. In the case of CPT-11 this has also led to an increase in overall survival. Improved therapy combinations and the delivery of the therapy directly to the liver by hepatic arterial infusion, either alone or in combination with intravenous delivery, all herald an improvement in the clinical outcome of patients with nonoperable liver metastases. These patients should be offered the best chemotherapy option available coupled, where appropriate, with liver resection.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Fluorouracilo/administración & dosificación , Neoplasias Hepáticas/secundario , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Fluorouracilo/efectos adversos , Humanos , Infusiones Intraarteriales , Infusiones Intravenosas , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Estadificación de Neoplasias , SobrevidaRESUMEN
Two meta-analyses were conducted to quantify the benefit of combining alpha-IFN to 5FU in advanced colorectal cancer in terms of tumour response and survival. Analyses were based on a total of 3254 individual patient data provided by principal investigators of each trial. The meta-analysis of 5FU +/- LV vs. 5FU +/- LV + alpha-IFN combined 12 trials and 1766 patients. The meta-analysis failed to show any statistically significant difference between the two treatment groups in terms of tumour response or survival. Overall tumour response rates were 25% for patients receiving no alpha-IFN vs. 24% for patients receiving alpha-IFN (relative risk, RR = 1.02), and median survivals were 11.4 months for patients receiving no alpha-IFN vs. 11.5 months for patients receiving alpha-IFN (hazard ratio, HR = 0.95). The meta-analysis of 5FU + LV vs. 5FU + alpha-IFN combined 7 trials, and 1488 patients. This meta-analysis showed an advantage for 5FU + LV over 5FU + alpha-IFN which was statistically significant in terms of tumour response (23% vs. 18%; RR = 1.26;P = 0.042), and of a borderline significance for overall survival (HR = 1.11;P = 0.066). Metastases confined to the liver and primary rectal tumours were independent favourable prognostic factors for tumour response, whereas good performance status, metastases confined to the liver or confined to the lung, and primary tumour in the rectum were independent favourable prognostic factors for survival. We conclude that alpha-IFN does not increase the efficacy of 5FU or of 5FU + LV, and that 5FU + alpha-IFN is significantly inferior to 5FU + LV, for patients with advanced colorectal cancer.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Fluorouracilo/uso terapéutico , Interferón-alfa/uso terapéutico , Neoplasias Colorrectales/mortalidad , Humanos , Leucovorina/uso terapéutico , Pronóstico , Modelos de Riesgos Proporcionales , Ensayos Clínicos Controlados Aleatorios como Asunto , Análisis de SupervivenciaAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Modelos Estadísticos , Teorema de Bayes , Carcinoma de Células Pequeñas/patología , Ensayos Clínicos Fase II como Asunto , Ensayos Clínicos Fase III como Asunto , Humanos , Neoplasias Pulmonares/patología , Estadificación de Neoplasias , Análisis de Supervivencia , Resultado del TratamientoAsunto(s)
Neoplasias del Colon/terapia , Antineoplásicos/uso terapéutico , Quimioterapia Adyuvante , Neoplasias del Colon/mortalidad , Neoplasias del Colon/patología , Supervivencia sin Enfermedad , Quimioterapia Combinada , Fluorouracilo/uso terapéutico , Humanos , Interferón-alfa/uso terapéutico , Levamisol/uso terapéutico , Metaanálisis como Asunto , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/terapia , Estadificación de Neoplasias , Educación del Paciente como AsuntoRESUMEN
The benefit of adjuvant therapy, such as 5-fluorouracil (5-FU) combined with leucovorin, is a matter of debate for patients with Dukes' B colon cancer. Several approaches have been taken to address this issue. Initially, studies were conducted to assess treatment benefits in both Dukes' B and Dukes' C patients. These studies identified an overall benefit of adjuvant treatment and enrolled enough Dukes' C patients to determine a treatment benefit for adjuvant 5-FU/leucovorin in this subpopulation. However, the individual studies were insufficiently powered to detect a treatment benefit in Dukes' B patients. An analysis of four separate studies (National Surgical Adjuvant Breast and Bowel project) compared the benefit of adjuvant treatment in Dukes' B patients with that in Dukes' C patients and showed similar relative reductions in mortality and disease-free survival in Dukes' B and in Dukes' C patients. The Liver Infusion Meta-Analysis Group also reported similar relative benefits from a portal vein infusion of 5-FU-based chemotherapy in Dukes' B and Dukes' C patients. The International Multicenter Pooled Analysis of Colon Cancer Trials B2 study, which combined data from patients with Dukes' B colon cancer in five separate trials, failed to show a statistically significant benefit of adjuvant 5-FU/leucovorin compared with surgery alone. We review the advantages and limitations of different approaches to detect treatment benefits in patients with Dukes' B colon cancer, and we argue that there is a need for a meta-analysis of all adjuvant trials to reliably address this question.
Asunto(s)
Neoplasias del Colon/tratamiento farmacológico , Antimetabolitos Antineoplásicos/uso terapéutico , Quimioterapia Adyuvante , Neoplasias del Colon/mortalidad , Neoplasias del Colon/patología , Neoplasias del Colon/cirugía , Supervivencia sin Enfermedad , Fluorouracilo/uso terapéutico , Humanos , Leucovorina/uso terapéutico , Metaanálisis como Asunto , Estudios Multicéntricos como Asunto , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Ensayos Clínicos Controlados Aleatorios como Asunto , Estadística como AsuntoRESUMEN
The aim of this randomized open-label study was to compare a bimonthly with a monthly regimen of 5-fluorouracil (5-FU) and leucovorin for the adjuvant treatment of colon and high-rectum adenocarcinoma. The bimonthly regimen was administered for 2 consecutive days every 14 days as d,L-leucovorin 200 mg/m2 or L-leucovorin 100 mg/m2 as a 2-hour infusion followed by 5-FU bolus of 400 mg/m2 and a 600 mg/m2 5-FU 22-hour continuous infusion (LVSFU2). In the monthly regimen, d,L-leucovorin 200 mg/m2 or L-leucovorin 100 mg/m2 15-minute infusion followed by a 400 mg/m2 15 minute 5-FU bolus was administered for 5 consecutive days every 28 days (FUFOL). Nine hundred five patients with recently resected stage B2 or C colon or high-rectum adenocarcinoma (inferior pole of the tumor subperitoneal) were recruited into the study. Patients were randomized in a 2 x 2 factorial design to receive either LV5FU2 or FUFOL for 24 or 36 weeks. Characteristics of the patients in the two different treatment groups were similar at baseline. Compliance was good. Mean 5-FU dose intensities were 930 mg/ m2/wk and 463 mg/m2/wk for LVSFU2 and FUFOL, respectively. The incidence of maximal grade III-IV toxicities for LVSFU2 and FUFOL was neutropenia 6% and 16% (P < .001), diarrhea 4% and 10% (P < .001), and mucositis 2% and 7% (P < .001), respectively. Maximum grade III-IV toxicities in the LV5FU2 treatment group were significantly lower than in the FUFOL group (10% v 26%; P < .001). Although patients in the LV5FU2 group received twice the dose of 5-FU compared with those in the FUFOL group, LV5FU2 was shown to be less toxic. Efficacy data will be available in 2001.