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1.
J Clin Oncol ; 41(3): 425-435, 2023 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-36649675

RESUMO

PURPOSE: Interferon alfa-2b (IFN alpha-2b) exhibits antitumor activity in metastatic melanoma and on this basis has been evaluated as an adjuvant therapy following surgery for deep primary (T4) or regionally metastatic (N1) melanoma. METHODS: A randomized controlled study of IFN alpha-2b (Schering-Plough, Kenilworth, NJ) administered at maximum-tolerated doses of 20 MU/m2/d intravenously (i.v.) for 1 month and 10 MU/m2 three times per week subcutaneously (SC) for 48 weeks versus observation, was conducted by the Eastern Cooperative Oncology Group (ECOG) in 287 patients. RESULTS: A significant prolongation of relapse-free survival (P = .0023, one-sided) and prolongation of overall survival (P = .0237, one-sided) was observed with IFN alpha-2b therapy in this trial, which is now mature with a median follow-up time of 6.9 years. The impact of treatment on relapse rate is most pronounced early during the treatment interval. The overall benefit of treatment in this trial was analyzed stratified by tumor burden and the presence or absence of microscopic nonpalpable and palpable regional lymph node metastasis. The benefit of therapy with IFN alpha-2b was greatest among node-positive strata. Toxicity of IFN alpha-2b required dose modification in the majority of patients, but treatment at > or = 80% of the scheduled dose was feasible in the majority of patients through the IV phase of treatment, and for more than 3 months of SC maintenance therapy. Discontinuation of treatment due to toxicity was infrequent after the fourth month of therapy. CONCLUSION: IFN alpha-2b prolongs the relapse-free interval and overall survival of high-risk resected melanoma patients. The increment in median disease-free survival (from 1 to 1.7 years) and overall survival (from 2.8 to 3.8 years) that results from this therapy is associated with a 42% improvement in the fraction of patients who are continuously disease-free after treatment with IFN (from 26% to 37%) in comparison to observation. IFN alpha-2b is the first agent to show a significant benefit in relapse-free and overall survival of high-risk melanoma patients in a randomized controlled trial.

2.
Anticancer Drugs ; 10(2): 245-8, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10211556

RESUMO

Despite reports that i.v. melphalan is active in the settings of conditioning regimens utilizing high-dose chemotherapy for autologous bone marrow transplantation and in isolated limb perfusion for the treatment of malignant melanoma, its activity at conventional doses has never been defined in this disease. We conducted a phase II study of conventional-dose i.v. melphalan (30 mg/m2) in 17 patients with metastatic melanoma. All patients were previously untreated with chemotherapy with performance status 0, 1 or 2. Forty-seven cycles were given with a median of two cycles. One patient was not evaluable due to early death. There were no responses in the 16 patients, resulting in a 0% response rate (95% confidence interval = 0-17%). We conclude that conventional-dose melphalan by i.v. administration has no appreciable activity in patients with metastatic malignant melanoma.


Assuntos
Antineoplásicos Alquilantes/administração & dosagem , Melanoma/tratamento farmacológico , Melanoma/secundário , Melfalan/administração & dosagem , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias das Glândulas Suprarrenais/secundário , Adulto , Idoso , Antineoplásicos Alquilantes/efeitos adversos , Neoplasias Encefálicas/secundário , Relação Dose-Resposta a Droga , Feminino , Neoplasias Gastrointestinais/secundário , Doenças Hematológicas/induzido quimicamente , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/secundário , Masculino , Melfalan/efeitos adversos , Pessoa de Meia-Idade , Neoplasias Cutâneas/patologia , Neoplasias de Tecidos Moles/secundário , Resultado do Tratamento
3.
Int J Radiat Oncol Biol Phys ; 39(4): 921-8, 1997 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-9369142

RESUMO

PURPOSE: Although an abundance of reports detail the successful use of definitive radiotherapy of the breast in the treatment in Stage I or II breast cancer, little data have been published concerning the use of lung density correction and its effect upon long-term outcome. As it has been the practice at the University of Michigan to routinely use lung density correction in the dose calculations to the breast, we retrospectively analyzed our results for local control, relapse-free, and overall survival. METHODS AND MATERIALS: Clinical records were reviewed of 429 women with Stage I or II breast cancer treated with lumpectomy, axillary dissection, and breast irradiation with or without systemic chemo/hormonal therapy. Tangential radiotherapy fields delivering 45 to 50 Gy were used to treat the entire breast. A boost was delivered in 95% of cases for a total tumor bed dose of 60 to 66 Gy. All treatment plans were calculated using a lung density correction. RESULTS: With a median follow up of 4.4 years, the 5-year actuarial rate of local control with local failure as the only site of first failure was 96% (95% CI 94-98%). Univariate analysis for local failure as only first failure found the following factors to statistically predict for increased risk of breast recurrence: young age (< or =35 years old), premenopausal status, tumor size >2 cm, positive family history, and positive microscopic margins. Multivariate analysis revealed young age and margin status to be the only factors remaining significant for local failure. The 5-year actuarial relapse-free survival was 85% (95% CI 81-89%); overall survival at 5 years was 90% (95% CI 87-94%). CONCLUSIONS: Lung density correction results in rates of local control, disease-free, and overall survival at 5 years that compare favorably with series using noncorrected unit density calculations. While we will continue to update our results with increasing follow-up, our 5-year data indicate that the use of lung-density correction for dosimetric accuracy does not compromise local control.


Assuntos
Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/radioterapia , Carcinoma Ductal de Mama/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/patologia , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Radioterapia (Especialidade)/métodos , Falha de Tratamento
4.
Int J Radiat Oncol Biol Phys ; 38(5): 941-7, 1997 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-9276358

RESUMO

OBJECTIVE: A rising prostate specific antigen (PSA) following treatment for adenocarcinoma of the prostate indicates eventual clinical failure, but the rate of rise can be quite different from patient to patient, as can the pattern of clinical failure. We sought to determine whether the rate of PSA rise could differentiate future local versus metastatic failure. METHODS AND MATERIALS: Two thousand six hundred sixty-seven PSA values from 400 patients treated with radiotherapy for localized adenocarcinoma of the prostate were analyzed with respect to PSA patterns and clinical outcome. Patients had received no hormonal therapy or prostate surgery and had > 4 PSA values post-treatment. PSA rate of rise, determined by the slope of the natural log, was classified as gradual [< 0.69 log(ng/ml)/year, or doubling time (DT) > 1 year], moderate [0.69-1.4 log(ng/ml)/year, or DT 6 months-1 year], or rapid [> 1.4 log(ng/ml)/year, or DT < 6 months]. RESULTS: Sixty-one percent of patients had non-rising PSA following treatment; 25% of patients with rising PSA developed clinical failure, and 93% of patients with clinical failure had rising PSA. The rate of rise discerned different clinical failure patterns. Local failure occurred in 23% of patients with moderate rate of rise versus 7% with gradual rise (p = 0.0001). Metastatic disease developed in 46% of those with rapid rise versus 8% with moderate rise (p < 0.0001). By multivariate analysis, in addition to rate of rise, PSA nadir and rate of decline predicted local failure; those with post-treatment nadir of 1-4 ng/ml were five times more likely to experience local failure than nadir < 1 ng/ml (p = 0.0002). Rapid rate of rise was the most significant independent predictor of metastatic failure. CONCLUSIONS: The rate of PSA rise following definitive radiotherapy can predict clinical failure patterns, with a rapidly rising PSA indicating metastatic recurrence and moderately rising PSA local recurrence. This information could potentially direct therapy; if the rise predicts metastatic failure hormonal therapy could be considered, while aggressive salvage therapy may benefit subclinical local recurrence identified by a moderate rate of PSA rise.


Assuntos
Adenocarcinoma/sangue , Adenocarcinoma/secundário , Recidiva Local de Neoplasia/sangue , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Adenocarcinoma/radioterapia , Diagnóstico Diferencial , Humanos , Masculino , Neoplasias da Próstata/radioterapia , Falha de Tratamento
5.
J Clin Oncol ; 14(1): 7-17, 1996 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8558223

RESUMO

PURPOSE: Interferon alfa-2b (IFN alpha-2b) exhibits antitumor activity in metastatic melanoma and on this basis has been evaluated as an adjuvant therapy following surgery for deep primary (T4) or regionally metastatic (N1) melanoma. METHODS: A randomized controlled study of IFN alpha-2b (Schering-Plough, Kenilworth, NJ) administered at maximum-tolerated doses of 20 MU/m2/d intravenously (i.v.) for 1 month and 10 MU/m2 three times per week subcutaneously (SC) for 48 weeks versus observation, was conducted by the Eastern Cooperative Oncology Group (ECOG) in 287 patients. RESULTS: A significant prolongation of relapse-free survival (P = .0023, one-sided) and prolongation of overall survival (P = .0237, one-sided) was observed with IFN alpha-2b therapy in this trial, which is now mature with a median follow-up time of 6.9 years. The impact of treatment on relapse rate is most pronounced early during the treatment interval. The overall benefit of treatment in this trial was analyzed stratified by tumor burden and the presence or absence of microscopic nonpalpable and palpable regional lymph node metastasis. The benefit of therapy with IFN alpha-2b was greatest among node-positive strata. Toxicity of IFN alpha-2b required dose modification in the majority of patients, but treatment at > or = 80% of the scheduled dose was feasible in the majority of patients through the IV phase of treatment, and for more than 3 months of SC maintenance therapy. Discontinuation of treatment due to toxicity was infrequent after the fourth month of therapy. CONCLUSION: IFN alpha-2b prolongs the relapse-free interval and overall survival of high-risk resected melanoma patients. The increment in median disease-free survival (from 1 to 1.7 years) and overall survival (from 2.8 to 3.8 years) that results from this therapy is associated with a 42% improvement in the fraction of patients who are continuously disease-free after treatment with IFN (from 26% to 37%) in comparison to observation. IFN alpha-2b is the first agent to show a significant benefit in relapse-free and overall survival of high-risk melanoma patients in a randomized controlled trial.


Assuntos
Interferon-alfa/uso terapêutico , Melanoma/terapia , Neoplasias Cutâneas/terapia , Doença Hepática Induzida por Substâncias e Drogas , Terapia Combinada , Esquema de Medicação , Feminino , Seguimentos , Humanos , Interferon alfa-2 , Interferon-alfa/efeitos adversos , Metástase Linfática , Masculino , Melanoma/mortalidade , Melanoma/secundário , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia , Doenças do Sistema Nervoso/induzido quimicamente , Modelos de Riscos Proporcionais , Proteínas Recombinantes , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Análise de Sobrevida , Taxa de Sobrevida
6.
Int J Radiat Oncol Biol Phys ; 33(2): 253-9, 1995 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-7673012

RESUMO

PURPOSE: Although the axilla is often treated with radiotherapy (RT) postoperatively when microscopic extracapsular extension (ECE) of lymph nodal metastases is present, little data are available to assess axillary failure in the absence of such treatment. As it has been the practice at this institution to withhold axillary irradiation in the presence of microscopic extracapsular spread, we retrospectively analyzed our results for axillary recurrence, disease-free survival (DFS), and overall survival (OS). METHODS AND MATERIALS: Clinical records were reviewed of 82 women with Stage II node positive breast cancer treated with lumpectomy, axillary dissection, and RT in addition to systemic chemo/hormonal therapy. Axillary surgery consisted of a level I, II, +/- III dissection, with a median of 16.5 nodes removed. Tangential radiotherapy fields were used to treat the breast. All patients were also treated with an abbreviated supraclavicular field with the lateral border medial to the humeral head. Pathological sections were available for review in 72 of the 82 women. RESULTS: Twenty-seven of 72 (37.5%) had evidence of ECE; 45 of 72 (62.5%) had metastatic carcinoma confined within the nodal capsule. Clinical characteristics were comparable between the patients with and without ECE with the exception of (a) pathologic subtype, with a greater percentage of infiltrating ductal tumors associated with ECE (p = 0.044), and (b) number of positive lymph nodes, with 93% of patients without ECE having one to three positive nodes vs. only 56% among patients with ECE (p < 0.001). With a median follow-up of 40 months, 1 of 27 patients (4%) with ECE experienced an axillary failure as a component of first failure compared to 0 of 45 patients without ECE (p = 0.4). There were no isolated axillary failures. Five-year disease-free survival (72% without ECE vs. 57% with ECE, p = 0.12) and overall survival (83% vs. 53%, respectively, p = 0.068) suggested a less favorable outcome for patients with ECE. CONCLUSIONS: Microscopic ECE appears to be associated with increased axillary involvement and decreased survival rather than subsequent axillary failure. Our data suggest that radiotherapy to a dissected axilla may be omitted for the sole indication of microscopic extracapsular disease.


Assuntos
Neoplasias da Mama/patologia , Metástase Linfática/patologia , Axila , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Excisão de Linfonodo , Metástase Linfática/radioterapia , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia , Falha de Tratamento
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