RESUMO

A phase II trial was performed to assess the efficacy and toxicity of a combination of ifosfamide (IFX), cisplatin (CDDP), and vinorelbine (VNB) as neoadjuvant chemotherapy (NAC) for untreated advanced cervical carcinoma (ACC). Between October 1995 and February 1998, 40 patients were entered in this study. Their median age was 43 years (range: 23-74 years). International Federation of Gynecology and Obstetrics stages were: IIB, 23; IIIB, 13; and IVA, 4. Therapy consisted of: IFX 2,000 mg/m2 1-hour (H) IV infusion days 1 to 3; 2-mercaptoethanesulfonic acid sodium salt (mesna) 400 mg/m2 IV bolus H 0 and 4, and 800 mg/m2 by mouth H 8, days 1 to 3; VNB 25 mg/m2 20-minute IV infusion days 1 and 8; and CDDP 75 mg/m2 IV day 3. Cycles were repeated every 28 days for a total of three courses. Both staging and response (R) assessment were performed by a multidisciplinary team. An objective response (OR) was observed in 24 of 40 patients (60%; 95% confidence interval, 45-75%). Four patients achieved complete response (CR) (10%); 20 partial response (50%); 12 patients stable disease (30%); and 4 progressive disease (10%). Eight of 24 patients (33%) with OR underwent radical surgery, and histologic CRs were recorded in 2 of them. The remaining patients received definitive radiotherapy after NAC. The dose-limiting toxicity was myelosuppression. Leukopenia occurred in 32 patients (80%) and was grade III or IV in 14 patients (36%). Peripheral neuropathy occurred in 9 patients (22%), whereas myalgias occurred in 10 (25%). Constipation was observed in 9 patients (23%); emesis occurred in 35 patients (88%). There were no therapy-related deaths. These results indicate that IFX/CDDP/VNB is an active combination for ACC with moderate toxicity. Implementation of this regimen in a multimodal therapy protocol deserves further study.

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RESUMO

PURPOSE: To evaluate the efficacy and toxicity of a combination of vinorelbine (VNB) and paclitaxel (PTX) as first-line chemotherapy in metastatic breast carcinoma (MBC). PATIENTS AND METHODS: Between August 1995 and August 1997, 49 patients with untreated MBC received a regimen that consisted of VNB 30 mg/m2 in a 20-minute intravenous (IV) infusion on days 1 and 8 and PTX 135 mg/m2 in a 3-hour IV infusion (starting 1 hour after VNB) on day 1. Cycles were repeated every 28 days. The median age of the patients was 52 years, and 59% of patients were postmenopausal. Median performance status was 1. Dominant sites of disease were soft tissue in 6%, bone in 29%, and viscera in 65%. RESULTS: Objective responses were recorded in 27 of 45 assessable patients (60%; 95% confidence interval, 46% to 74%). Complete remissions occurred in three patients (7%), and partial remissions occurred in 24 patients (53%). No change was recorded in 12 patients (27%), and progressive disease occurred in six patients (13%). The median time to treatment failure was 7 months, and median survival duration was 17 months. The limiting toxicity was myelosuppression, mainly leukopenia in 49 patients (100%) (grade 1 to grade 2, four patients; grade 3, 30 patients; and grade 4, 15 patients). Neutropenia was observed in 100% of patients (grade 1 to grade 2, three patients; grade 3, 11 patients; grade 4, 35 patients). Two treatment-related deaths due to febrile neutropenia were observed in patients with massive liver involvement. Peripheral neurotoxicity developed in 33 patients (67%) (grade 1, 25 patients; grade 2, eight patients); there were no grade 3 or grade 4 episodes. CONCLUSION: The combination of VNB-PTX showed significant activity as first-line chemotherapy for patients with MBC. Myelosuppression was the dose-limiting side effect, whereas neurotoxicity was mild to moderate.

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A phase II trial was conducted to evaluate the efficacy and toxicity of a modulation of 5-fluorouracil (5-FU) by methotrexate (MTX) (with leucovorin (LV) rescue) as first-line chemotherapy in patients with locally advanced (inoperable) or metastatic gastric carcinoma. From July 1993 through August 1996, 36 patients with advanced gastric carcinoma received a regimen that consisted of: MTX 200 mg/m2 diluted in 250 ml normal saline by intravenous infusion over 20 minutes at hour 0; 5-FU 1,200 mg/m2 intravenous push injection at hour 20. Beginning 24 hours after MTX administration all patients received LV 15 mg/m2 intramuscularly every 6 hours for six doses. Cycles were repeated every 15 days. One patient was not assessable for response. Objective regression was observed in 15 of 37 patients (43%; 95% confidence interval, 26%-60%). One patient (3%) achieved complete response and 14 (40%) achieved partial response. No change was recorded in 14 patients (40%) and progressive disease was noted in six patients (17%). The median time to treatment failure was 7 months and the median survival was 12 months. Toxicity was within acceptable limits but one therapy-related death resulting from severe leukopenia occurred. The dose-limiting toxicity was mucositis. Five episodes of grade 3 or 4 stomatitis were observed and caused dosage modifications of MTX and 5-FU. Biochemical modulation of 5-FU by MTX appears as an attractive modality in patients with advanced gastric cancer. Further investigation both in experimental and clinical fields is needed to clearly define its role and to design the best modulatory strategy.

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PURPOSE: A phase II trial was performed to evaluate the efficacy and toxicity of vinorelbine (VNB) as first-line chemotherapy for metastatic breast carcinoma. PATIENTS AND METHODS: Between August 1991 and February 1993, 45 patients with metastatic breast cancer were entered onto the study. Therapy consisted of VNB 30 mg/m2 diluted in 500 mL of normal saline administered as a 1-hour intravenous infusion. Injections were repeated weekly until evidence of progressive disease (PD) or severe toxicity developed. RESULTS: One patient was considered not assessable for response. An objective response (OR) was observed in 18 of 44 patients (41%; 95% confidence interval, 26% to 56%). Three patients (7%) had a complete response (CR) and 15 (34%) had a partial response (PR). The median time to treatment failure for the entire group was 6 months (range, 1 to 15), and the median duration of response was 9 months (range, 1 to 15). The median survival duration has not been reached yet. There were no treatment-related deaths. The dose-limiting toxicity was myelosuppression. Leukopenia occurred in 35 patients (78%) and was grade 3 or 4 in 16 (36%). Phlebitis was observed in 19 of 29 patients (66%) who did not have central implantable venous systems. Fifteen patients (33%) developed peripheral neurotoxicity. Myalgia occurred in 20 patients (44%). CONCLUSION: VNB is an active drug against metastatic breast cancer with moderate toxicity, which justifies further evaluation in association with other agents.

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En la mujer, el cáncer de mama representa el 25-30 por ciento de los tumores malignos siendo la enfermedad con mayor índice de mortalidad. Para identificar pacientes con carcinomas de mama de mal pronóstico, se usan diferentes parámetros relacionados con el tumor primario. De todos los parámetros usados rutinariamente, el grado de invasión tumoral en los ganglios linfáticos axilares es considerado uno de los más importantes. A pesar de ello, 30 por ciento de los pacientes con ganglios linfáticos libres de metástasis (considerados como de buen pronóstico) presentam recurrencia y mueren dentro de los 10 años de realizado el diagnóstico. Esto, al igual que otras observaciones, permiten concluir que los parámetros usados de rutina no serían suficientes - por sí solos - para predecir el curso de la enfermedad tumoral. Gracias a los últimos avances de la biología celular y molecular los eventos cruciales de la carcinogenesis, progresión tumoral y la metástasis están siendo analizados a nivel molecular. En algunos tumores estos adelantos ya están siendo incorporados a la páctica clínica. Recientemente se ha observado que, en determinados tumores, anormalidades de varios genes están correlacionados con el pronóstico de cada paciente. Por medio de la determinación de diferentes macromoléculas marcadoras, los laboratorios de biología molecular puedem brindar importante información pronóstica y de ayuda en al selección de las estrategias terapéuticas. Entre estos nuevos marcadores podemos citar: amplificación y/o sobreexpresión de oncogenes, secreción aumentada de factores de crecimiento, el índice de proliferación celular y la ploidía, proteinas inducidas por los estrógenos, expresión de moléculas relacionadas con el proceso de matástasis, proteínas asociadas con la resistencia farmacológica, etc. En este artículo realizamos un breve análisis de la metodología utilizada para evaluar estos marcadores tumorales y mencionamos algunas de sus aplicaciones clínicas. Nos acercamos al momento en el cual el diagnóstico clínico deberá realizarse a nivel molecular. Esto será posible combinando la histopatología convencional con las técnicas modernas de biología celular y molecular. Esta nueva información llevará a una reevaluación de los sistemas de los tumores, que no estarán basados en la aparencia morfológica o en el origen de las células, sino por la caracterización de sus genes asociados con estadios particulares de cada tumor (AU)

Assuntos

RESUMO

En la mujer, el cáncer de mama representa el 25-30 por ciento de los tumores malignos siendo la enfermedad con mayor índice de mortalidad. Para identificar pacientes con carcinomas de mama de mal pronóstico, se usan diferentes parámetros relacionados con el tumor primario. De todos los parámetros usados rutinariamente, el grado de invasión tumoral en los ganglios linfáticos axilares es considerado uno de los más importantes. A pesar de ello, 30 por ciento de los pacientes con ganglios linfáticos libres de metástasis (considerados como de buen pronóstico) presentam recurrencia y mueren dentro de los 10 años de realizado el diagnóstico. Esto, al igual que otras observaciones, permiten concluir que los parámetros usados de rutina no serían suficientes - por sí solos - para predecir el curso de la enfermedad tumoral. Gracias a los últimos avances de la biología celular y molecular los eventos cruciales de la carcinogenesis, progresión tumoral y la metástasis están siendo analizados a nivel molecular. En algunos tumores estos adelantos ya están siendo incorporados a la páctica clínica. Recientemente se ha observado que, en determinados tumores, anormalidades de varios genes están correlacionados con el pronóstico de cada paciente. Por medio de la determinación de diferentes macromoléculas marcadoras, los laboratorios de biología molecular puedem brindar importante información pronóstica y de ayuda en al selección de las estrategias terapéuticas. Entre estos nuevos marcadores podemos citar: amplificación y/o sobreexpresión de oncogenes, secreción aumentada de factores de crecimiento, el índice de proliferación celular y la ploidía, proteinas inducidas por los estrógenos, expresión de moléculas relacionadas con el proceso de matástasis, proteínas asociadas con la resistencia farmacológica, etc. En este artículo realizamos un breve análisis de la metodología utilizada para evaluar estos marcadores tumorales y mencionamos algunas de sus aplicaciones clínicas. Nos acercamos al momento en el cual el diagnóstico clínico deberá realizarse a nivel molecular. Esto será posible combinando la histopatología convencional con las técnicas modernas de biología celular y molecular. Esta nueva información llevará a una reevaluación de los sistemas de los tumores, que no estarán basados en la aparencia morfológica o en el origen de las células, sino por la caracterización de sus genes asociados con estadios particulares de cada tumor

Assuntos

RESUMO

The incidence of breast cancer is 25-30% of all malignant female tumors and represents the highest rate of mortality. To define those breast cancer patients at higher risk several prognostic factors are routinally evaluated in the primary tumor. Among them, the presence and degree of tumor involvement in axillary lymph node is one of the most powerful prognostic indicator. However, around 30% of node negative patients (good prognosis group) have recurrences and die within the next 10 years from diagnosis. Therefore, there is a need for markers to better discriminate biologic differences in the primary tumors. The techniques of molecular biology are shedding new insight into the subcellular pathology of malignancy. The crucial events of carcinogenesis, tumor progression, and metastatic spread are coming into focus at a molecular level. In some tumors, these advances in the laboratory are beginning to have applications at the bedside. Recently, abnormalities in the copy number and expression of several genes have been correlated with prognosis of individual patients with selected types of cancer. Molecular biology laboratories can provide useful predictive information that can be used to influence decision on the selection of treatment and to estimate a better risk stratification. Among these new markers are: oncongene amplification and/or over-expression, growth factors, cellular proliferation rate and ploidy, estrogens induced proteins, expression of metastasis related molecules, drug resistance associated proteins, etc. In this article we attempt to present a brief evaluation of a new technology that promises to add greater precision in evaluating molecular tumor markers and we mention some of its clinical applications.(ABSTRACT TRUNCATED AT 250 WORDS)

Assuntos

RESUMO

The incidence of breast cancer is 25-30

of all malignant female tumors and represents the highest rate of mortality. To define those breast cancer patients at higher risk several prognostic factors are routinally evaluated in the primary tumor. Among them, the presence and degree of tumor involvement in axillary lymph node is one of the most powerful prognostic indicator. However, around 30

of node negative patients (good prognosis group) have recurrences and die within the next 10 years from diagnosis. Therefore, there is a need for markers to better discriminate biologic differences in the primary tumors. The techniques of molecular biology are shedding new insight into the subcellular pathology of malignancy. The crucial events of carcinogenesis, tumor progression, and metastatic spread are coming into focus at a molecular level. In some tumors, these advances in the laboratory are beginning to have applications at the bedside. Recently, abnormalities in the copy number and expression of several genes have been correlated with prognosis of individual patients with selected types of cancer. Molecular biology laboratories can provide useful predictive information that can be used to influence decision on the selection of treatment and to estimate a better risk stratification. Among these new markers are: oncongene amplification and/or over-expression, growth factors, cellular proliferation rate and ploidy, estrogens induced proteins, expression of metastasis related molecules, drug resistance associated proteins, etc. In this article we attempt to present a brief evaluation of a new technology that promises to add greater precision in evaluating molecular tumor markers and we mention some of its clinical applications.(ABSTRACT TRUNCATED AT 250 WORDS)