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1.
J Fr Ophtalmol ; 29(7): 741-9, 2006 Sep.
Artículo en Francés | MEDLINE | ID: mdl-16988624

RESUMEN

INTRODUCTION: We conducted a retrospective study on the clinical factors influencing the local and general prognosis of patients treated for uveal melanoma with a preliminary analysis of the prognostic value of monosomy 3. PATIENTS: and method: The patients sent to Curie Institute for uveal melanoma have a complete initial clinical evaluation, conservative management by radiotherapy or enucleation, and local and general long-term follow-up. Over the last 5 years, the status of chromosome 3 has been assessed by FISH in the tumors of enucleated patients. Findings concerning the initial workup, treatment, and follow-up are recorded prospectively. We conducted a retrospective study with multivariate analysis of the clinical factors influencing local recurrence, ocular conservation metastasis, and survival and studied the effect of monosomy 3. RESULTS: A total of 2241 patients were registered with a median follow-up of 72 months. Of these patients, 92.8% had conservative management with iodine 125 brachytherapy or proton beam therapy and 7.2% of the patients had enucleation (n=160). Tumors from 120 patients were studied for the status of chromosome 3 by FISH. The overall survival rate was 76.3% and the metastatic rate was 19.5%. The clinical factors influencing survival were the size and location of the tumor, age of the patient, gender, and initial treatment. The factors influencing the metastatic risk were the same plus retinal detachment and local recurrence. Monosomy 3 was a significant risk factor for metastatic disease. DISCUSSION: This study found the usual risk factors with the difference that location on the equator seems to be of worse prognosis than ciliary body involvement for survival and metastasis. In addition, the initial retinal detachment appears to be a risk factor for local recurrence and metastasis. At present, the evaluation of chromosome 3 is available for enucleated tumors but it could probably be done on needle biopsy performed during conservative management as well. CONCLUSION: This study confirms previous results on the prognostic factors of uveal melanoma and on the value of monosomy 3. The increasingly precise identification of a group of high-risk patients should allow us to propose adjuvant therapy and to adapt follow-up.


Asunto(s)
Melanoma/terapia , Neoplasias de la Úvea/terapia , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos
2.
J Infus Chemother ; 6(3): 149-51, 1996.
Artículo en Inglés | MEDLINE | ID: mdl-9229328

RESUMEN

A total of 55 patients with measurable colorectal metastatic carcinoma were studied to evaluate the impact on toxicity, response, and survival of protracted venous infusion (PVI) 5-FU 200 mg/m2 per day with Cis-DDP 80 mg/m2 or carboplatin 300 mg/m2 every 3 weeks, 1-hour infusion. Patients received continuous uninterrupted therapy until there were signs or symptoms of toxicity. Both 5-FU and cisplatin were withheld when patients experienced grade II stomatitis and diarrhea, severe nausea or vomiting not controlled by standard antiemetic therapy, and clinically significant hand-foot syndrome. The toxicity was neurological (20% grade 2 and 3) hematological (13% grade 2) and dermatological (11% grade 2). The overall response (CR+PR) was 24% with a median survival of 13 months. The results of our study show that there is no improvement in response rate, response duration or survival compared with historical trials. However, this study does confirm the valuable palliative role of the protracted 5-FU infusion treatment. Colorectal carcinoma is one of the most common neoplasms in Western societies, being second only to lung cancer as a cause of death from malignancy. The management of nonmetastatic primary disease in surgical, with adjuvant chemotherapy for those at high risk of relapse. However, for those with metastatic disease at diagnosis or recurrent disease after resection, cytotoxic chemotherapy is the treatment of choice and fluorouracil (5-FU) is the most active cytotoxic agent in this disease, with a response rate of approximately 20%. Efforts to improve the response rate have focused on the use of agents to modulate 5 FU. The Southwestern Oncology Group (SWOG) study reported by Leichman et al. (1) and a study from the United Kingdom by Hill et al. (2) compared conventional FU to modulated FU and found no improvement in response rate or survival. In the SWOG study, two different schedules of bolus FU and LV were compared with bolus FU alone and to continuous infusion FU administered alone or modulated by LV or PALA. In this study, the results obtained with bolus FU were superior to most of the studies in the literature: The response rate was 26%, and the median survival was 14 months. The high- and low-dose LV and FU groups showed response rates and survival similar to bolus FU alone. However, in 12 previously reported randomized studies comparing FU and LV or FU alone, nine reported that the combination of FU and LV produced significant increases in response rates and two reported significant increase in survival (3, 4). Many of these trials used the dose schedules reported in the SWOG trial. Protracted venous infusion (PVI) 5-FU has been shown to have superior efficacy with less toxicity in colorectal cancer when compared to bolus 5-FU and synergy between cisplatin and 5-FU has been demonstrated in vitro. Consequently, we have investigated the efficacy of the combination of bolus cis or carboplatin and PVI 5 FU in 55 patients with advanced colorectal cancer using survival, response rate, symptomatic response, and toxicity as study endpoints.


Asunto(s)
Carboplatino/uso terapéutico , Cisplatino/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Fluorouracilo/uso terapéutico , Adulto , Anciano , Antimetabolitos Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/secundario , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Tasa de Supervivencia , Resultado del Tratamiento
3.
Cancer ; 77(7): 1315-23, 1996 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-8608509

RESUMEN

BACKGROUND: This retrospective study evaluates the results of a regimen of high-dose intrathecal methotrexate and the prognostic factors for the response in patients with meningeal from breast carcinoma. METHODS: From 1979 to 1994, 68 breast carcinoma patients were diagnosed with meningeal carcinomatosis at a mean age of 52 years. All but two had previous metastatic involvement. The proportion of lobular and ductal carcinomas was balanced. Malignant cells were present in cerebrospinal fluid (CSF) samples from 61 patients, whereas the 7 remaining patients had increased CSF protein associated with computerized tomographic scan evidence of meningeal metastases. From 1989, 41 of the patients received a regimen of high-dose intrathecal methotrexate with systemic folinic acid rescue (HD-MTX+FA): intrathecal MTX, 15 mg daily x 5 days, repeated every 2 weeks, and intrathecal hydrocortisone acetate, 125 mg on Day 1, and folinic acid, 10 mg intramuscularly 12 hours after each MTX injection. Systemic treatment and radiation therapy were usually associated. Patients treated before 1988 received intrathecal MTX in conventional doses (15 mg once a week). RESULTS: Clinical objective response, defined as a neurological improvement for at least one month, was achieved in 17 patients (41%) and stabilization in 14 (34%) treated with the HD-MTX+FA regimen. The response rate was significantly higher compared with that of the group treated with the conventional doses (P = 0.03). Median survival was 14 weeks for patients treated with the HD-MTX+FA regimen, compared with 7 weeks for patients who received conventional doses of MTX (P = 0.01). Grade 3 or 4 neutropenia was the main toxicity that occurred in 16 16 patients (39%) treated with the HD-MTX+FA regimen, and in 7 patients (33%) treated with conventional doses of MTX. In a univariate analysis, three parameters were singled out as having a favorable prognostic value for response to therapy; controlled systemic disease at diagnosis (P < 0.05), low initial CSF protein level (P < 0.05), and concomitant systemic chemotherapy during intrathecal therapy (P < 0.02). Multivariate analysis was not performed because the sample size was too small. CONCLUSIONS: Although this study was retrospective, the intrathecal HD-MTX+FA regimen appears to be a more efficient strategy than conventional doses of MTX to induce neurologic improvement and perhaps better survival. It should be recommended in combination with systemic chemotherapy for selected patients with meningeal carcinomatosis from breast carcinoma who are likely to benefit from intensive therapy, i.e., patients with a CSF protein level less than 5 g/L and in whom systemic disease has been controlled.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/patología , Carcinoma/tratamiento farmacológico , Carcinoma/secundario , Neoplasias Meníngeas/tratamiento farmacológico , Neoplasias Meníngeas/secundario , Adulto , Anciano , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Hidrocortisona/administración & dosificación , Hidrocortisona/análogos & derivados , Inyecciones Espinales , Leucovorina/administración & dosificación , Metotrexato/administración & dosificación , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos
4.
Eur J Cancer ; 31A(12): 1969-75, 1995 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-8562150

RESUMEN

The purpose of the present paper was to evaluate correlations between clinical response to chemotherapy and outcome in a subgroup analysis of premenopausal patients with tumours considered too large for breast conserving surgery, treated with primary chemotherapy (n = 200) from a previously published trial (Scholl S.M., Fourquet A., Asselain B, et al. Eur J Cancer 1994, 30A, 645-652). Objective response rates amounted to 65% following four courses. In a multivariate Cox regression analysis, comparing seven parameters, the following variables were associated with poor survival: clinically involved nodes [N1b:RR: 2.7 (95% CI 1.3-5.3)], the failure to respond to chemotherapy [D:RR: 2.62 (95% CI 1.3-5)] and a raised S phase fraction [SPF > 5%: RR: 2.4 (95% CI 1.2-5)]. Parameters associated with increased metastatic recurrence rates, by order of entry in the model, were: young age [< 35: RR: 2.46 (95% CI 1.2-5)], large clinical tumour size [T3: RR: 2.02 (95% CI 1.2-3.4)], poor histological grade (SBR III: RR: 1.93 (95% CI 1.1-3.3)] and the failure to respond to chemotherapy [D: RR: 1.91 (95% CI 1-3.4)]. The assessment of both tumour cell proliferation rates as well as possibly drug resistance markers (although not available in the present study) should be helpful in selecting patients likely to benefit from intensified chemotherapy regimens. The most accurate predictor of response in the present study appeared to be the response to chemotherapy treatment itself.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Adulto , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Quimioterapia Adyuvante , Ciclofosfamida/administración & dosificación , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Estudios de Seguimiento , Humanos , Mastectomía , Análisis Multivariante , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia , Pronóstico , Tasa de Supervivencia , Resultado del Tratamiento
5.
Eur J Cancer ; 30A(5): 645-52, 1994.
Artículo en Inglés | MEDLINE | ID: mdl-8080680

RESUMEN

The aim of this study was to assess a potential advantage in survival by neoadjuvant as compared to adjuvant chemotherapy. 414 premenopausal patients with T2-T3 N0-N1 M0 breast cancer were randomised to receive either four cycles of neoadjuvant chemotherapy (cyclophosphamide, doxorubicin, 5-fluorouracil), followed by local-regional treatment (group I) or four cycles of adjuvant chemotherapy after primary irradiation +/- surgery (group II). Surgery was limited to those patients with a persisting mass after irradiation, and aimed to be as conservative as possible. 390 patients were evaluable. With a median follow-up of 54 months, we observed a statistically significant difference (P = 0.039) in survival in favour of the neoadjuvant chemotherapy group. A similar trend was seen when the time to metastatic recurrence was evaluated (P = 0.09). At this stage, no difference in disease-free interval or local recurrence between these two groups could be observed. The mean total dose of chemotherapy administered was similar in both groups. On average, group I had more intensive chemotherapy regimes (doxorubicin P = 0.02) but fewer treatment courses (P = 0.008) as compared to the treated patients in group II. Haematological tolerance was reduced when chemotherapy succeeded to exclusive irradiation. Breast conservation was identical for both groups at the end of primary treatment (82 and 77% for groups I and II, respectively). Of the 191 evaluable patients in the neoadjuvant treatment arm, 65% had an objective response (> 50% regression) following four cycles of chemotherapy. The objective response rate to primary irradiation (55 Gy) was 85%. Improved survival figures in the neoadjuvant treatment arm could be the result of the early initiation of chemotherapy, but we cannot exclude that this difference might be attributable to a slightly more aggressive treatment. So far, the trend in favour of decreased metastases was not statistically significant. The local control appeared similar in both subgroups.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Premenopausia , Adulto , Neoplasias de la Mama/mortalidad , Quimioterapia Adyuvante , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Esquema de Medicación , Femenino , Fluorouracilo/administración & dosificación , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia
6.
Presse Med ; 22(3): 104-8, 1993 Jan 30.
Artículo en Francés | MEDLINE | ID: mdl-8493214

RESUMEN

Between March 1985 and December 1987, 34 women who had advanced adenocarcinoma of the ovary with macroscopic residual disease entered in a phase II trial of chemotherapy. Treatment consisted of a 3-month induction with monthly ifosfamide combined with 5-fluorouracil and high-dose cisplatin, and a maintenance treatment with ifosfamide, 5-fluorouracil, cisplatin and hexamethylmelamine in monthly cycles. At the end of the treatment patients with complete remission were evaluated by surgery. Neurotoxicity was a limiting factor, and treatment had to be prematurely withdrawn in 10 patients. The above treatment was found to be effective with a 94 percent objective response rate, a 54-month median survival and a 51-month median relapse-free survival. Because of the neurotoxicity, a shorter therapy and the use of neuroprotective agents may be envisaged.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Cisplatino/uso terapéutico , Neoplasias Ováricas/tratamiento farmacológico , Adenocarcinoma/mortalidad , Adenocarcinoma/cirugía , Adulto , Anciano , Altretamina/efectos adversos , Altretamina/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Evaluación de Medicamentos , Femenino , Fluorouracilo/efectos adversos , Fluorouracilo/uso terapéutico , Estudios de Seguimiento , Humanos , Ifosfamida/efectos adversos , Ifosfamida/uso terapéutico , Persona de Mediana Edad , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/cirugía , Cuidados Posoperatorios , Inducción de Remisión
7.
Eur J Cancer ; 27(12): 1668-71, 1991.
Artículo en Inglés | MEDLINE | ID: mdl-1782080

RESUMEN

Primary chemotherapy in localised breast cancer may prevent tumour spread during surgical treatment and reduce proliferation of micrometastases. A randomised clinical trial, in 196 premenopausal and postmenopausal patients with operable (T2-3, N0-1b) breast cancer, was started in November 1983 at the Institut Curie to compare neoadjuvant and adjuvant regimens of chemotherapy with radiotherapy with or without surgery. The patients have been followed up for 35-70 months (median 54). A neoadjuvant group received two monthly cycles of intravenous doxorubicin/cyclophosphamide/5-fluorouracil before locoregional therapy and four cycles subsequently. Six monthly cycles following locoregional therapy were administered to the adjuvant group. Because of inclusion of postmenopausal and/or node-negative patients, compliance was less than optimal in 39 patients who were analysed separately according to actual dose received. Tumour response, evaluated after two cycles of neoadjuvant chemotherapy, was significantly associated with dose (P = 0.003). Survival showed a slight non-significant advantage for the neoadjuvant group. Survival plotted by actual dose was also similar. Neoadjuvant chemotherapy was safe and at least as effective as the adjuvant regimen. Patients have been accrued to a subsequent larger trial of chemotherapy as first-line treatment.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/mortalidad , Quimioterapia Adyuvante , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Persona de Mediana Edad , Pronóstico
8.
Bull Cancer ; 73(3): 279-87, 1986.
Artículo en Francés | MEDLINE | ID: mdl-3756364

RESUMEN

Thirty-four patients with histologically proven metastatic breast cancer, were included in this phase II trial. They were given a five day course of continuous infusion of 5 fluoro-uracile at the daily dose of 500 mg/m2 associated with vindesine 2 mg/m2 on day 2 and 5, cyclophosphamide 300 mg/m2 on day 2 and 5. The treatment was repeated every 15 days after haematological and biological assay. Twenty-six patients were objectively resistant to previous cytotoxic chemotherapy including adriamycin and 6 patients had recently received adjuvant therapy. A major objective response was observed in 17 cases (50%) (4 complete responses, 13 responses greater than 50%) and a response less than 50% in 7 cases. The median duration of response is over 8 months. After 8 months of median follow-up, the median of survival is not defined.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/sangre , Neoplasias de la Mama/sangre , Neoplasias de la Mama/patología , Quimioterapia del Cáncer por Perfusión Regional , Ciclofosfamida/administración & dosificación , Evaluación de Medicamentos , Femenino , Fluorouracilo/administración & dosificación , Humanos , Cinética , Persona de Mediana Edad , Metástasis de la Neoplasia , Vindesina/administración & dosificación
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