RESUMO
BACKGROUND: The American College of Surgeons Oncology Group sought to confirm the efficacy of a novel interferon-based chemoradiation regimen in a multicenter phase II trial. PATIENTS AND METHODS: Patients with resected (R0/R1) adenocarcinoma of the pancreatic head were treated with adjuvant interferon-alfa-2b (3 million units s.c. on days 1, 3, and 5 of each week for 5.5 weeks), cisplatin (30 mg/m(2) i.v. weekly for 6 weeks), and continuous infusion 5-fluorouracil (5-FU; 175 mg·m(2)/day for 38 days) concurrently with external-beam radiation (50.4 Gy). Chemoradiation was followed by two 6-week courses of continuous infusion 5-FU (200 mg·m(2)/day). The primary study end point was 18-month overall survival from protocol enrollment (OS18); an OS18 ≥65% was considered a positive study outcome. RESULTS: Eighty-nine patients were enrolled. Eighty-four patients were assessable for toxicity. The all-cause grade ≥3 toxicity rate was 95% (80 patients) during therapy. No long-term toxicity or toxicity-related deaths were noted. At 36-month median follow-up, the OS18 was 69% [95% confidence interval (CI) 60% to 80%]; the median disease-free survival and overall survival were 14.1 months (95% CI 11.0-20.1 months) and 25.4 months (95% CI 23.4-34.1 months), respectively. CONCLUSIONS: Notwithstanding promising multi-institutional efficacy results, further development of this regimen will require additional modifications to mitigate toxic effects.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Terapia Combinada , Feminino , Fluoruracila/administração & dosagem , Humanos , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/radioterapia , Neoplasias Pancreáticas/cirurgia , Proteínas Recombinantes , Análise de SobrevidaRESUMO
Records from 653 patients treated between 1991 and 1998 in the Oncology Practice Patterns Study (OPPS) were analyzed to determine contemporary chemotherapy delivery patterns in patients with intermediate-grade non-Hodgkin's lymphoma (NHL). Of the 653 patient records reviewed, 90 (14%) omitted an anthracycline or mitoxantrone (Novantrone) from primary therapy. Among patients receiving CHOP (cyclophosphamide [Cytoxan, Neosar], doxorubicin HCl, vincristine [Oncovin], prednisone) or CNOP (cyclophosphamide, mitoxantrone, vincristine, prednisone), 134 (27%) of 492 received an average relative dose intensity of less than 80% of the literature-referenced dose, due either to an inadequate planned or delivered dose. Of 181 advanced-stage patients with responsive disease, 28 (15%) failed to receive at least six treatment cycles. Overall, 283 (43%) of 653 patients potentially received suboptimal chemotherapy due either to choice of regimen or chemotherapy delivered. Patient age > or = 65 years and cardiac comorbidity appeared to have the greatest influence on a physician's decision regarding chemotherapy administration. Among the 492 patients who received CHOP or CNOP, 235 (48%) experienced a delay or reduction in chemotherapy dose (usually neutropenia-related), 100 (20%) developed mucositis, and 116 (24%) were hospitalized for febrile neutropenia. Growth factor was administered to 261 patients (53%), and its primary prophylactic use was associated with a significant reduction in the incidence of hospitalizations for febrile neutropenia in all patient subgroups receiving appropriate chemotherapeutic dose intensity (P = .02). This assessment of chemotherapy delivery to patients with intermediate-grade NHL showed significant variation from current standards. Further analysis of factors influencing chemotherapy delivery might improve therapeutic outcomes.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Substâncias de Crescimento/uso terapêutico , Humanos , L-Lactato Desidrogenase/análise , Linfoma não Hodgkin/enzimologia , Masculino , Pessoa de Meia-Idade , Mitoxantrona/administração & dosagem , Mitoxantrona/efeitos adversos , Neutropenia/induzido quimicamente , Prednisolona/administração & dosagem , Prednisolona/efeitos adversos , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Valores de Referência , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Tempo , Vincristina/administração & dosagem , Vincristina/efeitos adversosAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pancreáticas/terapia , Pancreaticoduodenectomia , Radiossensibilizantes/uso terapêutico , Antimetabólitos Antineoplásicos/administração & dosagem , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Fluoruracila/administração & dosagem , Humanos , Interferon-alfa/administração & dosagem , Neoplasias Pancreáticas/mortalidade , Radioterapia Adjuvante , Análise de Sobrevida , Resultado do Tratamento , GencitabinaRESUMO
OBJECTIVE: To assess the high-frequency sonographic characteristics of ductal carcinoma in situ of the breast. METHODS: In a retrospective review, we identified 18 patients with biopsy-proven pure ductal carcinoma in situ who had received mammographic and high-frequency sonographic examinations at transducer frequencies of 8-15 MHz, 8-5 MHz and 5 to 13 MHz [corrected]. RESULTS: All 18 patients had mammographically identified calcifications. Four (22%) of the 18 had either asymmetric focal mammographically identified densities or masses with the calcifications. These calcifications were identified sonographically in 17 (94%) of the 18 patients. In 9 (50%) of 18 patients, the calcifications were associated with sonographically detected malignant masses, and in 3 (17%) of 18 patients the calcifications were within focally dilated ducts. Lesions that had masses or dilated ducts visible on sonography represented 9 (82%) of 11 of the grade 3 neoplasms and only 2 (28%) of 7 of the grade 1 and 2 tumors. This difference was statistically significant (P < .039). CONCLUSIONS: Our study showed that ductal carcinoma in situ may appear on sonography as calcifications, masses, or focally dilated ducts. Those lesions that were associated with masses or dilated ducts on sonography were more likely high-grade histologic specimens.
Assuntos
Neoplasias da Mama/diagnóstico por imagem , Calcinose/diagnóstico por imagem , Carcinoma in Situ/diagnóstico por imagem , Carcinoma Ductal de Mama/diagnóstico por imagem , Ultrassonografia Mamária , Neoplasias da Mama/patologia , Carcinoma in Situ/patologia , Carcinoma Ductal de Mama/patologia , Feminino , Humanos , Mamografia , Estudos RetrospectivosRESUMO
BACKGROUND: Based on a 2-year survival of 43%, the Gastrointestinal Tumor Study Group (GITSG) recommended adjuvant 5-FU-based chemoradiation for resected patients with adenocarcinoma of the pancreatic head. Here we report improved survival over the GITSG protocol with a novel adjuvant chemoradiotherapy based on interferon-alpha (IFNalpha). METHODS: From July 1993 to September 1998, 33 patients with adenocarcinoma of the pancreatic head underwent pancreaticoduodenectomy (PD) and subsequently went on to adjuvant therapy (GITSG-type, n = 16) or IFNalpha-based (n = 17) typically given between 6 and 8 weeks after surgery. The latter protocol consisted of external-beam irradiation at a dose of 4,500 to 5,400 cGy (25 fractions per 5 weeks) and simultaneous three-drug chemotherapy consisting of (1) continuous infusion 5-FU (200 mg/m2 per day); (2) weekly intravenous bolus cisplatin (30 mg/m2 per day); and (3) IFNalpha (3 million units subcutaneously every other day) during the 5 weeks of radiation. This was then followed by two 6-week courses of continuous infusion 5-FU (200 mg/m2 per day, given weeks 9 to 14 and 17 to 22). Risk factors for recurrence and survival were compared for the two groups. RESULTS: A more advanced tumor stage was observed in the IFNalpha-treated patients (positive nodes and American Joint Committee on Cancer [AJCC] stage III = 76%) than the GITSG group (positive nodes and stage III = 44%, P = 0.052). The 2-year overall survival was superior in the IFNalpha cohort (84%) versus the GITSG group (54%). With a mean follow-up of 26 months in both cohorts, actuarial survival curves significantly favored the IFNalpha group (P = 0.04). CONCLUSIONS: With a limited number of patients, this phase II type trial suggests better survival in the interferon group as compared with the GITSG group even though the interferon group was associated with a more extensive tumor stage. The 2-year survival rate in the interferon group is the best published to date for resected pancreatic cancer. The interferon/cisplatin/5-FU-based adjuvant chemoradiation protocol appears to be a promising treatment for patients who have undergone PD for adenocarcinoma of the pancreatic head.
Assuntos
Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Interferon-alfa/uso terapêutico , Neoplasias Pancreáticas/terapia , Pancreaticoduodenectomia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Cisplatino/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Radioterapia Adjuvante , Fatores de Risco , Análise de Sobrevida , Resultado do TratamentoAssuntos
Carcinoma Mucoepidermoide/diagnóstico por imagem , Carcinoma Mucoepidermoide/secundário , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Neoplasias Parotídeas/patologia , Medronato de Tecnécio Tc 99m , Humanos , Masculino , Pessoa de Meia-Idade , CintilografiaRESUMO
Cardiac tamponade due to lymphomatous involvement of the heart is a dramatic and unusual complication. Because of their nonspecific clinical presentation, these tumors are seldom diagnosed antemortem. We report the case of a patient with AIDS who presented with signs and symptoms of cardiac tamponade. Emergency pericardiocentesis followed by staging studies revealed large cell B-lymphocyte lymphoma confined to the pericardial space. With combination chemotherapy, a durable complete response was obtained. This case illustrates the potential benefit of aggressive treatment of extranodal non-Hodgkin's lymphoma in a patient with AIDS. The case is of particular interest because of the unusual development of isolated pericardial involvement as the sentinel sign of lymphoma.
Assuntos
Tamponamento Cardíaco/etiologia , Neoplasias Cardíacas/complicações , Linfoma Relacionado a AIDS/complicações , Linfoma Imunoblástico de Células Grandes/complicações , Pericárdio , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Cardíacas/tratamento farmacológico , Humanos , Linfoma Relacionado a AIDS/tratamento farmacológico , Linfoma Imunoblástico de Células Grandes/tratamento farmacológico , MasculinoRESUMO
A case of locally extensive perianal Paget's disease is presented. Initial wide local excision, guided by frozen sections, was inadequate. Multiple punch biopsies subsequently revealed extensive circumferential involvement of the anoderm by Paget's disease, making wide local excision difficult. Therefore, the patient was treated with combined chemoradiotherapy (5000 cGy, 5-fluorouracil, and mitomycin C). Fourteen months after treatment, the patient had a complete response.
Assuntos
Neoplasias do Ânus/tratamento farmacológico , Neoplasias do Ânus/radioterapia , Doença de Paget Extramamária/tratamento farmacológico , Doença de Paget Extramamária/radioterapia , Idoso , Neoplasias do Ânus/patologia , Terapia Combinada , Fluoruracila/uso terapêutico , Humanos , Masculino , Mitomicina , Mitomicinas/uso terapêutico , Doença de Paget Extramamária/patologia , Dosagem RadioterapêuticaRESUMO
The clinical course of 54 patients with small lymphocytic lymphoma (SL) was reviewed. The majority of patients had disseminated lymphoma at the time of diagnosis; 14 patients (26%) presented with Ann Arbor stage I and II disease. Five- and 10-year survival for all patients was 76% and 49%. The only clinicopathologic features identified that predicted a shortened survival were the presence or absence of systemic (B) symptoms (15% v 63% at 10 years, P = .01) and a diffuse rather than pseudofollicular nodal architecture (47% v 87% at 10 years, P = .04). Initial bone marrow involvement was not an adverse prognostic factor for patients who presented with stage III and IV disease. Ten patients developed a marked lymphocytosis consistent with progression to a leukemic phase (chronic lymphocytic leukemia [CLL]). These ten patients had a median initial lymphocyte count of 2,790, compared with 1,580 for those patients who did not progress to CLL (P = .0001). Developing CLL did not adversely affect survival (P = .48). Thirty-seven patients were treated with various combinations of radiation and chemotherapy; 17 patients received no initial therapy. Ten-year freedom from relapse (FFR) for stage I and II patients treated with irradiation was 80% and 62%; FFR for stage III and IV treated patients was 11%. Despite the marked differences in FFR, no statistically significant difference in survival could be demonstrated between the various stages. Selected patients with advanced SL received no initial therapy; these patients had a 10-year survival that was not statistically different from the immediately treated stage III and IV patients. Patients with stage I and II SL should be treated with irradiation; prolonged FFR and possibly cure of the disease can be achieved in these patients.
Assuntos
Leucemia Linfocítica Crônica de Células B/patologia , Análise Atuarial , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/imunologia , Leucemia Linfocítica Crônica de Células B/terapia , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , PrognósticoRESUMO
Forty-four adult patients with lymphoblastic lymphoma (LBL) were treated according to one of two protocols. Both included (1) induction with cyclophosphamide, doxorubicin, vincristine, prednisone, and L-asparaginase; (2) CNS prophylaxis; and (3) maintenance therapy with methotrexate (MTX) and 6-mercaptopurine. In the second protocol, CNS prophylaxis began earlier than in the first protocol and included cranial irradiation and intrathecal (IT) MTX rather than simultaneous high-dose systemic and IT MTX. The overall response rate was 100% (95% complete). With a 26-month median follow-up, the 1-and 3-year actuarial freedom from relapse (FFR) for the composite patient group was 70% and 56%, respectively. The incidence of CNS relapse was reduced from 31% in the first protocol to 3% in the second protocol (P = .04, Gehan). Patients can be assigned retrospectively to low (n = 19) and high (n = 25) risk prognostic groups, as indicated by a multivariate analysis of pretreatment prognostic factors. High-risk is defined by Ann Arbor stage IV disease with bone marrow or CNS involvement or initial serum lactate dehydrogenase (LDH) concentration of greater than 300 IU/L (normal, less than 200). FFR of low- and high-risk groups at 5 years are 94% and 19%, respectively (P = .0006). Low-risk patients are highly curable using this approach to adult LBL. More intensive treatment for high-risk patients is warranted.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Encefálicas/patologia , Esquema de Medicação , Feminino , Humanos , L-Lactato Desidrogenase/sangue , Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/radioterapia , Masculino , Estadiamento de Neoplasias , Fenótipo , Prognóstico , Risco , Doenças da Medula Espinal/patologiaRESUMO
To test the biologic activity of 13-cis retinoic acid (13-CRA) in patients with myelodysplastic states (MDS), we administered 13-CRA orally (2.5 mg/kg/d initially, escalated to 4 mg/kg/d) for 8 weeks to 15 consecutive patients. Eight of 15 patients (53%) experienced an increase in peripheral granulocyte counts of greater than 20% (range, 22% to 700%). In five patients, the absolute increase in peripheral granulocyte count was greater than 500 cells/microL. Two of 15 patients experienced a decrease in the circulating granulocyte count of greater than or equal to 20%. Comparable values for peripheral platelet counts were 27% (4/15 patients) greater than 20% increase and 33% (5/15 patients) greater than 20% decrease. No patient experienced a major change in erythrocyte transfusion requirement while receiving 13-CRA in comparison with pretreatment status. Thirteen patients had morphologic and cytogenetic evaluation of marrow cells before 13-CRA treatment, and with one exception, marrow morphologic and cytogenetic abnormalities persisted following 13-CRA administration. The exception occurred in the patient with the most dramatic response, whose granulocyte count increased from 400 to 2,800 cells/microL along with a normalization of the leukocyte alkaline phosphatase score, a morphologic improvement in granulocyte maturation, and a disappearance of the initial chromosome abnormality. These changes did not persist after cessation of 13-CRA administration, but were reproduced following drug readministration. No patients experienced serious decrements in peripheral blood counts or leukemic transformation while receiving 13-CRA. All patients had mild to marked dermatologic toxicity (cheilosis, skin dryness). No other major toxicity was encountered. We conclude that 13-CRA may be safely administered and may increase peripheral granulocyte counts in a proportion of patients with MDS.
Assuntos
Síndromes Mielodisplásicas/tratamento farmacológico , Tretinoína/uso terapêutico , Adulto , Idoso , Transfusão de Sangue , Medula Óssea/patologia , Ensaios Clínicos como Assunto , Feminino , Granulócitos/citologia , Humanos , Isotretinoína , Cariotipagem , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/sangue , Síndromes Mielodisplásicas/genética , Contagem de PlaquetasRESUMO
A series of 26 lymphoblastic lymphomas (LLs) and 13 T cell acute lymphoblastic leukemias (ALLs) were investigated using a battery of monoclonal antibodies applied to tissue frozen sections. Twenty-one of the LLs were of T lineage. All but one of the T cell LLs were of immature thymic phenotype, mostly corresponding to stage II cortical thymocyte development. The T cell LLs expressed Leu-1 in 100%, Leu-4 and Leu-9 in 95%, and Leu-5 in 85% of the cases. The high percentage of Leu-4 expression in this series is probably due to detection of cytoplasmic antigen with our methods. One LL was of pre-B or B cell and two cases were of common ALL phenotype. Two cases were of undefined phenotype, expressing markers of both B and T cell differentiation. Pediatric cases showed a greater tendency toward T cell phenotype than did adult cases. The cases of T cell ALL were immunophenotypically similar to the cases of T cell LL but showed a tendency toward a more immature phenotype.
Assuntos
Antígenos de Neoplasias/análise , Leucemia Linfoide/imunologia , Linfoma/imunologia , Linfócitos T/imunologia , Adolescente , Adulto , Fatores Etários , Anticorpos Monoclonais , Antígenos de Diferenciação de Linfócitos T , Antígenos de Superfície/análise , Criança , Pré-Escolar , Humanos , Micose Fungoide/imunologia , Fenótipo , Neoplasias Cutâneas/imunologiaRESUMO
Twenty-eight patients with advanced squamous carcinoma of the uterine cervix received cisplatin, bleomycin, and mitomycin after failure of surgery and/or irradiation to control disease. Six patients (21%) achieved responses (two complete; four partial), ranging from 3 to 7+ months. Toxicity was acceptable for most patients; however, dose reduction because of myelosuppression was frequently required. Bleomycin was delivered by continuous iv infusion, and no significant pulmonary toxicity was observed. Although this combination of drugs has activity in advanced squamous carcinoma of the uterine cervix, the addition of cisplatin to bleomycin and mitomycin did not significantly increase the clinical response rate.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias do Colo do Útero/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bleomicina/administração & dosagem , Carcinoma de Células Escamosas/secundário , Cisplatino/administração & dosagem , Avaliação de Medicamentos , Feminino , Doenças Hematológicas/induzido quimicamente , Humanos , Infusões Parenterais/instrumentação , Injeções Intravenosas , Pneumopatias/induzido quimicamente , Pessoa de Meia-Idade , Mitomicinas/administração & dosagem , Recidiva Local de Neoplasia/tratamento farmacológicoRESUMO
We studied 40 consecutive patients with advanced germ-cell carcinoma and elevated serum levels of human chorionic gonadotropin (HCG) to assess the prognostic value of the magnitude of the decline in HCG levels after chemotherapy. If serum levels failed to become normal after the first chemotherapy cycle and if the day-22 HCG level/day-1 level was greater than 1/200 (0.005), an incomplete response to chemotherapy could be predicted with a sensitivity of 90% and a predictive value of 94%. Conversely, if the day-22 level was within normal limits, or if the day-22 level/day-1 level was less than 1/200, a successful response to chemotherapy (defined as a 1-year disease-free interval following cessation of chemotherapy) could be predicted with a sensitivity of 95% and a predictive value of 91% after one chemotherapy cycle. Overall, the long-term response to chemotherapy was correctly predicted in 37 of 40 patients (p less than 0.0001, compared with actual patient outcome using the chi-squared test).
Assuntos
Gonadotropina Coriônica/sangue , Neoplasias Embrionárias de Células Germinativas/sangue , Neoplasias Testiculares/sangue , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Coriocarcinoma/sangue , Coriocarcinoma/tratamento farmacológico , Feminino , Humanos , Masculino , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Gravidez , Prognóstico , Neoplasias Testiculares/tratamento farmacológicoRESUMO
Of 38 adult patients with idiopathic thrombocytopenic purpura followed an average of more than 12 years, 15 suffered splenectomy failure or postsplenectomy recurrence of thrombocytopenia. Nine of the 15 also received immunosuppressive agents, and four of the nine failed such therapy. In eight of these 15 treatment failures normal or safe platelet counts were achieved in a subsequent three to 12 year period during which they received no therapy. The frequency of spontaneous recovery of satisfactory platelet levels in adults with idiopathic thrombocytopenic purpura in whom treatment failed may have negative implications for very vigorous or longstanding immunosuppressive therapeutic attempts in certain cases.