RESUMO
BACKGROUND: The liver is the predominant site of metastases among patients with advanced neuroendocrine tumors (NETs). Prior retrospective studies have reported high response rates in patients treated with transarterial embolization (TAE). NETs are highly vascular and are known to express vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR). We hypothesized that administration of sunitinib, a VEGFR inhibitor, following TAE would extend progression-free survival (PFS). PATIENTS AND METHODS: Patients with metastatic NETs to the liver underwent a series of selective TAEs followed by sunitinib (until disease progression or maximum of 12 months). Radiographic response (by RECIST), survival, and safety parameters were monitored. RESULTS: Thirty-nine patients were enrolled. The overall response rate was 72% [95% confidence interval (CI), 0.58-0.86]. Median PFS was 15.2 months. Rates of overall survival (OS) at 1 and 4 years were 95% (95% CI, 0.88-1.00) and 59% (95% CI, 0.38-0.80), respectively. A significant 34% rise in serum VEGF was observed following the initial TAE (P = 0.03). CONCLUSIONS: Hepatic TAE is a highly active treatment option for patients with metastatic NETs to the liver. Embolization stimulates release of VEGF into the circulation. Sunitinib, an oral VEGFR inhibitor, can be safely administered following embolization. The high rates of PFS and OS associated with this sequence of therapies are encouraging.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Embolização Terapêutica , Artéria Hepática , Indóis/uso terapêutico , Neoplasias Intestinais/terapia , Neoplasias Hepáticas/terapia , Pirróis/uso terapêutico , Resinas Acrílicas/uso terapêutico , Adulto , Idoso , Inibidores da Angiogênese/farmacologia , Intervalo Livre de Doença , Feminino , Gelatina/uso terapêutico , Humanos , Indóis/farmacologia , Neoplasias Intestinais/sangue , Neoplasias Intestinais/mortalidade , Neoplasias Intestinais/patologia , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Tumores Neuroendócrinos , Modelos de Riscos Proporcionais , Pirróis/farmacologia , Estatísticas não Paramétricas , Sunitinibe , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/sangueRESUMO
24 patients with advanced, histologically proven cancer were treated with difluoromethylornithine 2.25 g/m2 orally every 6 h for the first 7 days of each 4-week treatment cycle. These patients also received daily i.m. doses of recombinant human alpha 2a-interferon (IFN) on Days 3 through 7 of each cycle. IFN doses of 3, 6, 12, 24, 36, and 48 X 10(6) units/m2 have been studied utilizing three patients at each daily dose level. Three additional patients have been observed at each of the two highest doses for better toxicity definition. This combination produced slight transient declines in leukocyte and platelet counts and transient rises in serum aspartate aminotransferase; however, these changes were no more pronounced at the higher IFN doses than at daily doses of 6 X 10(6) units/m2. Mild nausea and vomiting occurred in most patients and mild diarrhea also was common at all IFN dose levels. Chills, fever, myalgia, lethargy and fatigue, and anorexia were also observed at all IFN doses; however, lethargy and fatigue (lassitude) seemed to be the major factor which limited patient tolerance of IFN to 48 X 10(6) units/m2 daily. No ototoxicity was identified clinically or audiometrically and no life-threatening toxicity has occurred. Initial Phase II studies in melanoma are currently in progress.
Assuntos
Antineoplásicos/uso terapêutico , Eflornitina/administração & dosagem , Interferon Tipo I/administração & dosagem , Interferon-alfa/administração & dosagem , Neoplasias/terapia , Adulto , Idoso , Avaliação de Medicamentos , Eflornitina/efeitos adversos , Feminino , Humanos , Interferon alfa-2 , Interferon-alfa/efeitos adversos , Masculino , Pessoa de Meia-Idade , Proteínas RecombinantesRESUMO
Somatostatin (SS) receptor status was investigated in the tumor tissues from 62 patients with carcinoid tumors and 15 patients with islet cell carcinomas using receptor autoradiography techniques with two different iodinated somatostatin analogues as radioligands, a [Leu8, DTrp22, Tyr25]somatostatin-28 and a somatostatin octapeptide, Tyr3-octreotide. The carcinoid tumors were either primaries (n = 32) or metastases (n = 43), sampled as surgical specimens or as small needle liver biopsies. Fifty-four of 62 carcinoid patients had SS receptor-positive tumors (87%). All 15 islet cell carcinoma patients had positive tumors (4 primaries, 11 metastases), i.e., 3 vipomas, 3 insulinomas, 2 glucagonomas, 1 gastrinoma, 2 polyfunctional tumors, and 4 nonfunctioning tumors. Saturation and competition experiments on tissue sections revealed saturable, high affinity binding sites pharmacologically specific for bioactive SS analogues. In a majority of the tumors, the receptors were densely distributed and were always homogeneously found in the whole tumor. All except two tumors were labeled with both radioligands. Multiple liver metastases (n = 16) from three different patients were all shown to contain a comparable amount of receptors. SS receptors could be demonstrated even in very small tissue samples of liver metastases obtained by percutaneous liver biopsies (mean weight, 6.8 mg). The majority of the eight SS receptor-negative carcinoids were mainly bronchial carcinoids (n = 5), usually poorly differentiated. On the contrary, SS receptor-positive cases were never found to be anaplastic. All tumors except one from patients pretreated with octreotide (3 days to 3.8 years) were SS receptor positive. In the majority of carcinoids or islet cell carcinomas, the SS receptor status correlated with the in vivo biochemical response (hormone inhibition) to octreotide. These data demonstrate (a) the high prevalence of SS receptors in the primary tumors of both carcinoids and islet cell carcinomas, (b) their presence in metastases as well, (c) their continuous expression even during long term octreotide therapy, (d) the possibility of measuring SS receptors in percutaneous needle liver biopsies, and (e) the evidence of their functionality. This study therefore suggests that tumoral SS receptors may be the likely molecular basis for octreotide action and may be an important parameter for predicting the therapeutic efficacy of SS analogues in carcinoids and islet cell carcinomas.
Assuntos
Adenoma de Células das Ilhotas Pancreáticas/análise , Tumor Carcinoide/análise , Neoplasias Pancreáticas/análise , Receptores de Neurotransmissores/análise , Adenoma de Células das Ilhotas Pancreáticas/tratamento farmacológico , Adenoma de Células das Ilhotas Pancreáticas/patologia , Biópsia por Agulha , Tumor Carcinoide/tratamento farmacológico , Tumor Carcinoide/patologia , Humanos , Octreotida/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Receptores de SomatostatinaRESUMO
For almost 30 years, 6-thioguanine (6-TG) has been administered p.o. for treatment of various human cancers, especially leukemias, even though the systemic availability of the drug given p.o. is known to be low and highly variable. Parenterally administered 6-TG has been studied in detail in humans only on a single-day intermittent schedule, although multiple-day intermittent schedules are known to produce maximal cytotoxic effects in several animal species. To develop a multiple-day regimen for parenteral 6-TG therapy, we carried out a dose-seeking and pharmacokinetic study of the drug given i.v. daily for 5 days in patients with various refractory advanced solid tumors. Dose-limiting myelosuppression without other significant toxicity occurred at 55-65 mg/m2 daily for 5 days. After i.v. administration at 65 mg/m2, the mean peak plasma concentration of 6-TG ranged from 6-10 microM. These concentrations are 8-300 times greater than peak plasma concentrations of 6-TG in plasma reported to occur after p.o. administration at 100 mg/m2. We suggest that the antitumor activity of 6-TG be reassessed against human cancers in regimens of i.v. administration on multiple-day intermittent schedules.
Assuntos
Neoplasias/tratamento farmacológico , Tioguanina/administração & dosagem , Adulto , Idoso , Esquema de Medicação , Avaliação de Medicamentos , Feminino , Hematopoese/efeitos dos fármacos , Humanos , Infusões Parenterais , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Tioguanina/metabolismoRESUMO
Twenty-seven patients with metastatic carcinoid tumor, 24 of whom had the malignant carcinoid syndrome, were treated with recombinant leukocyte A interferon at a planned dose of 24 x 10(6) U/m2. Twenty percent of patients with measurable tumor experienced an objective regression and 39% of those with the carcinoid syndrome experienced a reduction of more than 50% in urine 5-hydroxyindoleacetic acid (5HIAA) excretion. Flushing was partially or completely relieved in 65% of patients and diarrhea was relieved in 33%. Regrettably, these favorable treatment effects were transient in nature, with objective regressions persisting for a median of only 7 weeks and hormonal responses for a median of only 4 weeks. Any therapeutic gain experienced by these patients seemed to be outweighed by the frequency and severity of toxic reactions, which consisted primarily of chills and fever, fatigue, anorexia, weight loss, leukopenia, and abnormalities of liver function. Whereas other interferons, administration by alternative dosages and regimens, or incorporation of interferons into drug combinations may merit future study, we cannot recommend recombinant leukocyte A interferon, administered by the methods we employed, for routine therapy of the carcinoid tumor or syndrome.
Assuntos
Tumor Carcinoide/terapia , Interferon Tipo I/efeitos adversos , Síndrome do Carcinoide Maligno/terapia , Adolescente , Adulto , Idoso , Tumor Carcinoide/secundário , Avaliação de Medicamentos , Feminino , Humanos , Masculino , Proteínas RecombinantesRESUMO
Preclinical studies have demonstrated enhanced cytotoxic effects of 5-fluorouracil (5-FU) when given in conjunction with N-phosphonacetyl-L-aspartate (PALA) or thymidine in several murine systems. Early clinical studies have demonstrated significant delayed depletion of pyrimidine nucleotides in tumor biopsy specimens following systemic PALA administration and prolonged serum levels of 5-FU after thymidine administration. Each of these biochemical effects would be anticipated to augment the cytotoxic activity of 5-FU. A phase II trial of a timed sequential administration schedule of PALA, thymidine, and 5-FU was conducted in 37 patients with advanced measurable colorectal cancer. Ten of 37 patients (27%) experienced objective tumor responses with a median response duration of 22 weeks, and 18 patients (49%) had stable disease for a median duration of 20 weeks. Six of 13 patients (46%) with anaplastic histology and/or rapidly progressive tumors experienced high-quality tumor responses. Leukopenia and neurologic side effects were the primary toxicities, including one death caused by sepsis. This regimen has demonstrated striking alteration in the 5-FU dose-effect relationship and definite antitumor activity in patients with advanced colorectal cancer. Further trials in patients with anaplastic carcinomas of the colon or other anatomic sites should be considered.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias Retais/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ácido Aspártico/administração & dosagem , Ácido Aspártico/efeitos adversos , Ácido Aspártico/análogos & derivados , Ataxia/induzido quimicamente , Confusão/induzido quimicamente , Esquema de Medicação , Avaliação de Medicamentos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Infusões Parenterais , Masculino , Pessoa de Meia-Idade , Ácido Fosfonoacéticos/administração & dosagem , Ácido Fosfonoacéticos/efeitos adversos , Ácido Fosfonoacéticos/análogos & derivados , Timidina/administração & dosagem , Timidina/efeitos adversosRESUMO
OBJECTIVES: The hypothesis was that cardiac surgery for symptomatic carcinoid heart disease in conjunction with adjunctive therapy could improve the long-term outlook of patients with carcinoid heart disease. BACKGROUND: Patients with carcinoid heart disease have a dismal prognosis; most die of progressive right heart failure within 1 year after onset of symptoms. Improved therapies for the systemic manifestations of the carcinoid syndrome have resulted in symptomatic improvement and prolonged survival in patients without heart disease. METHODS: Twenty-six patients with symptomatic carcinoid heart disease underwent valvular surgery. Preoperative clinical, laboratory, Doppler echocardiographic and hemodynamic factors were evaluated. The survival of the surgical group was compared with that of a control group of 40 medically treated patients. RESULTS: There were nine perioperative deaths (35%), primarily from postoperative bleeding and right ventricular failure. Of the 17 surgical survivors, 8 were alive at a mean of 28 months of follow-up. The postoperative functional class of the eight surviving patients was substantially improved. Late deaths were primarily due to hepatic dysfunction caused by metastatic disease. The only predictor of operative mortality (p = 0.03) was low voltage on preoperative electrocardiography (limb lead voltage < or = 5 mm). Predictors of late survival included a lower preoperative somatostatin requirement and a lower preoperative urinary 5-hydroxy-indoleacetic acid level. There was a trend toward increased survival for the surgical group compared with the control group. CONCLUSIONS: Because new therapies have improved survival in patients with the malignant carcinoid syndrome, cardiac involvement has become a major cause of morbidity and mortality. Valve surgery is the only definitive treatment. Although cardiac surgery carries a high perioperative mortality, marked symptomatic improvement occurs in survivors. Surgical intervention should therefore be considered when cardiac symptoms become severe.
Assuntos
Doença Cardíaca Carcinoide/cirurgia , Próteses Valvulares Cardíacas , Valvas Cardíacas/cirurgia , Análise Atuarial , Bioprótese , Doença Cardíaca Carcinoide/diagnóstico , Doença Cardíaca Carcinoide/mortalidade , Feminino , Seguimentos , Próteses Valvulares Cardíacas/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Fatores de Tempo , Resultado do TratamentoRESUMO
The presence of transcripts for somatostatin receptor (SSTR) subtypes 1, 2, 3, and 4 was probed by reverse transcription and polymerase chain reaction in ribonucleic acid isolated from 46 malignant and 9 nonmalignant breast tissues, 15 carcinoid tumor tissues, and 13 renal cell carcinoma tissues. The transcripts for SSTR2 were amplified in all but 2 tissue samples, whereas transcripts for SSTR1, SSTR3, and SSTR4 were detected sporadically. In renal cell tumors, SSTR3 transcripts were completely absent. In breast cancer tissue, SSTR subtypes were transcribed independently of patient age, menstrual status, diagnosis, histological grade, and levels of estrogen receptor and progesterone receptor. The probability of finding transcripts for SSTR subtypes, P, was ranked differently for the three types of tumor tissues. For breast cancer, P2 > P3 = P1 > P4; for carcinoid tumors, P2 > P1 > P3 = P4; and for renal cell tumors, P2 > P1 > P4 > P3.
Assuntos
Neoplasias da Mama/metabolismo , Tumor Carcinoide/metabolismo , Carcinoma de Células Renais/metabolismo , Expressão Gênica , Neoplasias Renais/metabolismo , Receptores de Somatostatina/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Sequência de Bases , Neoplasias da Mama/cirurgia , Tumor Carcinoide/cirurgia , Carcinoma de Células Renais/cirurgia , Primers do DNA , DNA Complementar , Feminino , Humanos , Neoplasias Renais/cirurgia , Menopausa , Pessoa de Meia-Idade , Dados de Sequência Molecular , Reação em Cadeia da Polimerase/métodos , RNA Neoplásico/isolamento & purificação , RNA Neoplásico/metabolismo , Transcrição GênicaRESUMO
The glucagonoma syndrome is a rare disorder characterized by weight loss, necrolytic migratory erythema (NME), diabetes, stomatitis, and diarrhea. We identified 21 patients with the glucagonoma syndrome evaluated at the Mayo Clinic from 1975 to 1991. Although NME and diabetes help identify patients with glucagonomas, other manifestations of malignant disease often lead to the diagnosis. If the diagnosis is made after the tumor is metastatic, the potential for cure is limited. The most common presenting symptoms of the glucagonoma syndrome were weight loss (71%), NME (67%), diabetes mellitus (38%), cheilosis or stomatitis (29%), and diarrhea (29%). Although only 8 of the 21 patients had diabetes at presentation, diabetes eventually developed in 16 patients, 75% of whom required insulin therapy. Symptoms other than NME or diabetes mellitus led to the diagnosis of an islet cell tumor in 7 patients. The combination of NME and diabetes mellitus led to a more rapid diagnosis (7 months) than either symptom alone (4 years). Ten patients had diabetes mellitus before the onset of NME. No patients had NME clearly preceding diabetes mellitus. Increased levels of secondary hormones, such as gastrin (4 patients), vasoactive intestinal peptide (1 patient), serotonin (5 patients), insulin (6 patients, clinically significant in 1 only), human pancreatic polypeptide (2 patients), calcitonin (2 patients) and adrenocorticotropic hormone (2 patients), contributed to clinical symptoms leading to the diagnosis of an islet cell tumor before the onset of the full glucagonoma syndrome in 2 patients. All patients had metastatic disease at presentation. Surgical debulking, chemotherapy, somatostatin, and hepatic artery embolization offered palliation of NME, diabetes, weight loss, and diarrhea. Despite the malignant potential of the glucagonomas, only 9 of 21 patients had tumor-related deaths, occurring an average of 4.91 years after diagnosis. Twelve patients were still alive, with an average age follow-up of 3.67 years.
Assuntos
Glucagonoma , Neoplasias Pancreáticas , Adulto , Idoso , Diabetes Mellitus/etiologia , Diagnóstico Diferencial , Diarreia/etiologia , Eritema/etiologia , Feminino , Seguimentos , Glucagonoma/complicações , Glucagonoma/diagnóstico , Glucagonoma/mortalidade , Glucagonoma/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/terapia , Estomatite/etiologia , Análise de Sobrevida , Resultado do TratamentoRESUMO
Malignant carcinoid tumors are remarkably varied in their biologic behavior. The disease may be indolent for years with minimal or no symptoms. On the other hand, an acute carcinoid crisis with severe diarrhea, dehydration, and hypotension may develop in the patient. Patients with flushing and/or diarrhea, not responsive to standard symptomatic measures, may benefit from chemotherapy or hormonal therapy. Chemotherapy with single agents or combination chemotherapy may be associated with response rates ranging from 20 to 40 percent. Hepatic de-arterialization by ligation or occlusion is an effective means of inducing rapid tumor shrinkage for patients who have carcinoid tumors and hepatic dominant metastases. The addition of chemotherapy after induction of a partial remission with hepatic de-arterialization may prolong the duration of response, but this remains to be proven in prospective clinical trials. Hormonal therapy with the antiestrogen tamoxifen has been unsuccessful, but treatment of the carcinoid syndrome with a long-acting analogue of somatostatin has been strikingly effective.
Assuntos
Antineoplásicos/uso terapêutico , Tumor Carcinoide/tratamento farmacológico , Síndrome do Carcinoide Maligno/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ensaios Clínicos como Assunto , Ciproeptadina/uso terapêutico , Fenclonina/uso terapêutico , Artéria Hepática/cirurgia , Humanos , Interferons/uso terapêutico , Ligadura , Octreotida , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Tamoxifeno/uso terapêuticoRESUMO
Eighteen patients with unresectable carcinoma of the stomach whose known malignant disease was confined to structures immediately adjacent to the primary tumor and could be encompassed within a radiotherapy field were treated with an intensive sequential combined modality regimen. The regimen consisted of 5-FU plus adriamycin chemotherapy, followed by high dose megavoltage radiation therapy with 5-FU given as a radiation sensitizer, followed by maintenance chemotherapy with 5-FU plus adriamycin plus methyl CCNU (FAMe). Our primary objective was to determine patient tolerability. Severe and prolonged anorexia, nausea, and decreased performance status occurred during and after high dose radiotherapy given twice daily in 150-170 cGy (rad) fractions when given with 5-FU. Lengthening intervals between treatment segments, and the use of one daily dose of radiation therapy combined with 5-FU or two fractions daily without 5-FU seemed to decrease nutritional complications. Control of tumor at the primary site appeared to be achieved in most patients. Distant metastases represented the predominant mode of treatment failure with only two patients currently without progression of malignant disease. Our treatment regimen as initially conceived was too toxic for general use. Improved therapeutic results in locally unresectable gastric cancer will require the development of more effective therapy for occult distant metastases.
Assuntos
Adenocarcinoma/terapia , Neoplasias Gástricas/terapia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/radioterapia , Adulto , Idoso , Doxorrubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Lomustina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/radioterapiaRESUMO
When conventional modalities (external beam irradiation and chemotherapy +/- resection) are used in the treatment of locally advanced gastrointestinal malignancies, although useful palliation can be achieved in many patients, local control and long-term survival are infrequent. In recent trials, investigators have used fractionated external beam doses of 4500-5000 rad in 180 rad fractions in combination with irradiation boost techniques of intraoperative electrons, or intraoperative or transcatheter brachytherapy (+/- chemotherapy and resection). With colorectal and biliary cancer, both local control and long-term survival appear to be improved, compared to results achieved with conventional treatment. With pancreatic cancer, an apparent improvement has been noted with local control and median survival, but long-term survival has not been altered. For partially resected gastric cancer, the use of intraoperative irradiation has yielded five year survival rates of approximately 20%. With unresectable or residual gastric cancer, accelerated fractionation alone or in combination with chemotherapy has yielded excellent local control, but patients have died as a result of abdominal failure or lung metastases. Prevention of abdominal failures will be necessary to improve long-term survival with pancreatic and gastric cancer. Randomized trials by site are needed to determine if the observed differences seen in prospective nonrandomized trials are real or due to differences in case selection.
Assuntos
Neoplasias do Sistema Digestório/radioterapia , Neoplasias dos Ductos Biliares/radioterapia , Neoplasias do Colo/radioterapia , Terapia Combinada , Neoplasias do Sistema Digestório/mortalidade , Humanos , Metástase Neoplásica , Recidiva Local de Neoplasia , Inoculação de Neoplasia , Neoplasias Pancreáticas/radioterapia , Prognóstico , Neoplasias Retais/radioterapia , Neoplasias Gástricas/radioterapiaRESUMO
PURPOSE: Analyze patterns of failure, survival, and tolerance in patients with totally resected ductal adenocarcinoma of the pancreas treated with adjuvant irradiation alone or combined with chemotherapy. METHODS AND MATERIALS: The records of 29 patients treated with radiotherapy following curative resection of pancreas cancer at the Mayo Clinic were retrospectively reviewed. Twenty-two (76%) patients underwent a subtotal pancreatectomy (Whipple procedure), six (21%) a total pancreatectomy, and one (3.5%) a distal pancreatectomy. Twenty-six (90%) had lesions located in the head of the pancreas and three (10%) were located either in the body or tail. Twelve (41%) of the tumors were histologic Grade 3, 15 (52%) Grade 2, and two Grade 1. Contiguous invasion of adjacent tissues or organs was found in fifteen patients (52%) and seventeen (59%) had lymph node involvement. Greater than 75% of patients received more than 45 Gy, with a median dose of 54 Gy, and twenty-seven (93%) patients received concomitant 5-fluorouracil chemotherapy. RESULTS: The median survival was 22.8 months and the 2-year survival 48%. When survival was compared with that achieved with surgery alone in our institution, data suggested a doubling in both median and long-term survival with the addition of adjuvant treatment. Eighty-three percent of patients experienced tumor relapse with seventeen of 29 (59%) developing either liver metastases or peritoneal spread. In three patients, tumors recurred locally; one of one with microscopic residual disease after resection and two of 28 (7%) with negative margins (one of the two was treated with inadequate radiation portals). Patients tolerated adjuvant treatment with minimal acute toxicity consisting mostly of vomiting or nausea which, were controlled with medication in all patients. Chronic toxicity was acceptable; while 5 of 29 (17%) developed some form of possible treatment related complication, only one patient (3.5%) developed a small bowel obstruction. CONCLUSION: These results corroborate data in previous studies which have shown a survival benefit when adjuvant irradiation plus 5-fluorouracil is used in patients with completely resected ductal adenocarcinoma of the pancreas. The patterns of failure indicate that post-operative adjuvant treatment can effectively control disease locally but that future survival improvements will be achieved only by reducing the incidence of liver and peritoneal metastases.
Assuntos
Carcinoma Intraductal não Infiltrante/cirurgia , Fluoruracila/uso terapêutico , Neoplasias Pancreáticas/cirurgia , Radioterapia de Alta Energia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Intraductal não Infiltrante/tratamento farmacológico , Carcinoma Intraductal não Infiltrante/radioterapia , Terapia Combinada , Feminino , Humanos , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/radioterapia , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Because of the poor local control rates obtained with external beam irradiation +/- chemotherapy for locally advanced pancreatic cancer, our institution has used intraoperative radiation therapy (IORT) with electrons to deliver a single "boost" dose of radiation in 52 patients with biopsy-proven adenocarcinoma (primary, unresectable-49; primary, residual-2; and recurrent, unresectable-1). Patients received 4500-5000 rad of fractionated external beam irradiation and an IORT dose of 1750 rad (2 patients) or 2000 rad (50 patients). Acute and chronic tolerance have been acceptable. Documented local progression within either the external beam or IORT fields has been infrequent (3 of 42 evaluable patients or 7%), but there has been little, if any, change in median or long-term survival from that seen in external beam series. This is probably because of a high incidence of liver and peritoneal metastases with pancreatic cancer. A phase II pilot trial, which combines upper or total abdominal irradiation and infusion 5-FU with tumor nodal irradiation plus IORT, is in progress in our institution to evaluate tolerance and the relative incidence of abdominal failures.
Assuntos
Adenocarcinoma/radioterapia , Fluoruracila/uso terapêutico , Neoplasias Pancreáticas/radioterapia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/cirurgia , Terapia Combinada , Humanos , Período Intraoperatório , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Prognóstico , Dosagem Radioterapêutica , Radioterapia de Alta EnergiaRESUMO
From March 1981 to November 1987, 87 patients with histologically confirmed pancreatic adenocarcinoma, unresectable but confined to the pancreatic region, were randomized to two treatments. The standard treatment was 40-50 Gy external-beam radiation therapy (RT) to gross tumor plus potential microscopic tumor with a 5 Gy boost to gross tumor plus a 1.5-2.0 cm margin, using multiple fields and 5-fluorouracil (5-FU) 500 mg/m2/d intravenously by rapid infusion. The 5-FU was given each of the initial 3 days of each of three 20 Gy radiation courses. The experimental treatment used identical radiation fields, but the two Gy daily radiation fractions were administered in a continuous course to a total dose of 50 Gy. Hycanthone was administered 60 mg/m2 intravenously within 2 to 4 hr during each day of the 5-day course of infusions during the first and fifth weeks of radiation therapy. There was no statistically significant difference between treatment arms in survival (p = 0.82) or disease-free survival (p = 0.27). Seven percent of hycanthone-treated patients demonstrated hepatic toxicity which was usually mild in nature. There was, however, one death due to hepatic toxicity.
Assuntos
Adenocarcinoma/terapia , Fluoruracila/uso terapêutico , Hicantone/uso terapêutico , Neoplasias Pancreáticas/terapia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Estudos de Avaliação como Assunto , Feminino , Fluoruracila/administração & dosagem , Humanos , Hicantone/administração & dosagem , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/radioterapia , Estudos Prospectivos , Análise de Sobrevida , Taxa de SobrevidaRESUMO
Although usually associated with carcinoid tumors of the small intestine that have metastasized to the liver, the carcinoid syndrome is seen less frequently with primary tumors arising from other organs such as the lung, pancreas, thymus, stomach, and ovary. The clinical features, pathophysiology and diagnosis, and therapeutic considerations of this syndrome are presented. The management of carcinoid crisis and the results of recent chemotherapy trials are also discussed.
Assuntos
Síndrome do Carcinoide Maligno/terapia , HumanosRESUMO
A modified method for the preparation of a radiolabeled analog of somatostatin (123I-octreotide) is described. The pharmacokinetics and dosimetry of this analog were evaluated in patients with neuroendocrine tumors. Thirty patients had multiple blood and urine samples and sequential anterior and posterior whole-body scintigraphy up to 40 hr postinjection of 123I-octreotide. Region of interest analysis of the whole-body images was used to determine organ and tumor doses. The 123I-octreotide was rapidly cleared from the blood with a T 1/2 of 10 min by the hepatobiliary system. By 40 hr, approximately 55% was eliminated in the feces. The gallbladder wall received the highest dose (0.48 rad/mCi), with other organs receiving doses of 0.12 rad/mCi or less. Tumors were identified in 25 of 28 satisfactory studies. Tumor doses ranged from 0.1 to 0.6 rad/mCi. Calculations with 131I instead of 123I indicated that the gallbladder wall would receive 2 rad/mCi, while average tumor doses would range from 0.9 to 5.0 rad/mCi. Iodine-123-octreotide is a useful agent for the visualization of neuroendocrine tumors. The rapid washout of this agent from tumors precludes the possibility of radiotherapy with 131I-octreotide in these patients.
Assuntos
Neoplasias das Glândulas Endócrinas/metabolismo , Radioisótopos do Iodo/farmacocinética , Neoplasias do Sistema Nervoso/metabolismo , Octreotida/farmacocinética , Neoplasias das Glândulas Endócrinas/diagnóstico por imagem , Neoplasias das Glândulas Endócrinas/tratamento farmacológico , Feminino , Humanos , Radioisótopos do Iodo/administração & dosagem , Masculino , Pessoa de Meia-Idade , Neoplasias do Sistema Nervoso/diagnóstico por imagem , Neoplasias do Sistema Nervoso/tratamento farmacológico , Octreotida/administração & dosagem , Octreotida/uso terapêutico , CintilografiaRESUMO
The increased understanding of the neuroendocrine tumors at a cellular and molecular level has led to the development of new radiopharmaceuticals for imaging. Two of the imaging agents include 131I metaiodobenzylguanidine (131I-MIBG) and 111In-DTPA-D-Phe1-octreotide (111In-pentetreotide) each having specific localization in certain neuroendocrine tumors. The selective uptake of these radiopharmaceuticals by the tumor cells has generated interest in potential use for targeted radiotherapy for neuroendocrine tumors. 131I-MIBG has been used to treat patients with pheochromocytoma, neuroblastoma, carcinoid tumors, medullary thyroid carcinoma, and paragangliomas. The tumor responses have been variable with the most encouraging results being in patients with pheochromocytoma. The dose-limiting toxicity has been thrombocytopenia or granulocytopenia. 111In-pentetreotide has been used as therapy in only a few patients and has resulted in objective evidence of tumor responses. A therapeutic agent using a somatostatin analogue will most likely require radiolabeling with a beta- or possibly an alpha-emitting radionuclide to achieve significant and durable tumor responses.
Assuntos
Antineoplásicos/uso terapêutico , Radioisótopos de Índio/uso terapêutico , Radioisótopos do Iodo/uso terapêutico , Iodobenzenos/uso terapêutico , Tumores Neuroendócrinos/radioterapia , Somatostatina/análogos & derivados , 3-Iodobenzilguanidina , Humanos , Somatostatina/uso terapêuticoRESUMO
OBJECTIVE: To review the clinical features associated with hyperglucagonemia in malignant neuroendocrine tumors. MATERIAL AND METHODS: We retrospectively reviewed the medical records of patients with hyperglucagonemia encountered at our institution from Oct. 17, 1988, through February 1993 who had a fasting serum glucagon level of at least 120 pg/mL (twice the normal value). The 71 study patients also had no evidence of a secondary cause of hyperglucagonemia and had pathologic confirmation of a neuroendocrine tumor. RESULTS: The study group consisted of 46 men and 25 women with a median age of 57 years. Two patients had multiple endocrine neoplasia. Forty-nine patients had biochemically polyfunctional tumors, and 22 had hyperglucagonemia only. The most common initial symptoms were weight loss, abdominal pain, diarrhea, nausea, peptic ulcer disease, diabetes, and necrolytic migratory erythema (NME). Diabetes eventually developed in 25 patients and was associated with NME in 11. The highest median serum glucagon values occurred in patients with the glucagonoma syndrome or insulinomas, and the lowest median values were in those with carcinoid syndrome, Zollinger-Ellison syndrome, or diabetes without NME. Fasting glucagon and glucose measurements were not correlated. The most common hormonal syndromes were the Zollinger-Ellison syndrome and the glucagonoma syndrome. All the neuroendocrine tumors were malignant. Several methods of treatment, including surgical debulking, chemotherapy, somatostatin, and hepatic artery embolization, were used. Death occurred in 29 patients at a median of 2.79 years after diagnosis; 42 patients were alive at a median of 2.86 years after diagnosis. CONCLUSION: A mild degree of hyperglucagonemia can commonly be associated with multifunctional neuroendocrine tumors. The glucagonoma syndrome occurs in a few patients with malignant neuroendocrine tumors and hyperglucagonemia and is associated with very high serum glucagon levels. The correlation between serum glucagon levels and the development of diabetes is limited, and other factors such as insulin may be more important than hyperglucagonemia in the development of diabetes.
Assuntos
Glucagon/sangue , Tumores Neuroendócrinos/sangue , Adulto , Idoso , Glicemia/metabolismo , Tumor Carcinoide/sangue , Diabetes Mellitus/sangue , Feminino , Glucagonoma/sangue , Hormônios/sangue , Humanos , Insulinoma/sangue , Masculino , Pessoa de Meia-Idade , Neoplasia Endócrina Múltipla/sangue , Estudos Retrospectivos , Síndrome de Zollinger-Ellison/sangueRESUMO
The cause of testicular cancer, like most other cancers, is unknown. Certain risk factors such as cryptorchidism, carcinoma in situ, and a preceding contralateral testicular germ cell neoplasm are known to predispose a person to the subsequent development of a testicular malignant lesion. Familial testicular cancer has been debated as a potential and possibly independent risk factor. Evidence in favor of such a hypothesis, based on various genetic studies reported during the past few decades, is reviewed. We add to the existing literature our experience with six cases of familial testicular cancer encountered during a 10-year period, consisting of four father-and-son pairs, one pair of nontwin brothers, and a 23-year-old man who had a maternal uncle with a history of testicular cancer.