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1.
J Clin Oncol ; 19(19): 3967-75, 2001 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-11579118

RESUMO

PURPOSE: To evaluate oral topotecan as single-agent, second-line therapy in patients with ovarian cancer previously treated with a platinum-based regimen. PATIENTS AND METHODS: Patients (N = 116) received oral topotecan 2.3 mg/m2 daily for 5 days every 21 days. Eligibility criteria included histologic diagnosis of International Federation of Gynecology and Obstetrics stage III or IV epithelial ovarian cancer, bidimensionally measurable disease, prior platinum-containing chemotherapy, age > or = 18 years, performance status < or = 2, and life expectancy > or = 12 weeks. RESULTS: Overall response rate was 21.6% (25 of 116 patients). Median duration of response was 25.0 weeks; median time to response was 8.4 weeks. Median time to progression was 14.1 weeks; median survival was 62.2 weeks. Grade 4 neutropenia was experienced by 50.4% of patients in 13.4% of courses administered. Grade 4 thrombocytopenia was experienced by 22.1% of patients in 5.1% of courses. Grade 3 or 4 anemia was experienced by 29.2% of patients in 8.5% of courses. Most frequent nonhematologic toxicities were predominantly (> 90%) grade 1 or 2 and included nausea, alopecia, diarrhea, and vomiting. CONCLUSION: Second-line oral topotecan administered at 2.3 mg/m2 for 5 days every 21 days demonstrated activity in patients with progressive or recurrent ovarian cancer after first-line platinum-based chemotherapy. This activity was comparable to that seen in previous studies with intravenous topotecan. Grade 4 neutropenia was less frequent with oral topotecan than previously reported for intravenous topotecan. Oral topotecan is an active, tolerable, and convenient formulation of an established agent for the second-line treatment of advanced epithelial ovarian cancer and may also facilitate exploring prolonged treatment schedules.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Topotecan/uso terapêutico , Administração Oral , Adulto , Idoso , Antineoplásicos/efeitos adversos , Resistencia a Medicamentos Antineoplásicos , Feminino , Doenças Hematológicas/induzido quimicamente , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos Organoplatínicos/uso terapêutico , Neoplasias Ovarianas/patologia , Taxa de Sobrevida , Topotecan/efeitos adversos
2.
Am J Clin Pathol ; 116(1): 122-8, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11447742

RESUMO

Expression of CD44 standard form (CD44s) was evaluated by automated immunohistochemical analysis using the anti-CD44 A3D8 clone in 101 ovarian epithelial neoplasms including 82 primary tumors (64 carcinomas and 18 tumors of low malignant potential [LMP]), 9 lymph node metastases, 8 malignant ascites, and 2 peritoneal implants. Immunostaining was scored semiquantitatively. Tumors were graded according to the FIGO (International Federation of Gynecology and Obstetrics) classification system. Tumor stage and patient survival were determined from the patient records. While 9 of 18 LMP tumors expressed CD44s, only 15 of 64 carcinomas expressed it. In the carcinomas, univariate analysis revealed that decreased CD44s expression correlated with high tumor grade, advanced stage, and shortened survival. Loss of CD44s expression also was noted in the tumor cells in 8 of 9 lymph node metastases, 7 of 8 malignant ascites, and 1 of 2 implants. Multivariate analysis revealed that only tumor stage independently correlated with patient survival. Loss of CD44s expression determined by immunohistochemical analysis is more common in ovarian carcinomas than in LMP tumors; correlates with prognostic variables including tumor grade, stage, and survival; and may have an important role in the dissemination of ovarian cancer.


Assuntos
Carcinoma/metabolismo , Carcinoma/patologia , Receptores de Hialuronatos/metabolismo , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Análise de Sobrevida
3.
J Clin Oncol ; 19(5): 1275-8, 2001 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-11230468

RESUMO

PURPOSE: A phase II trial of paclitaxel was initiated in advanced nonsquamous carcinoma of the cervix to determine its activity in patients who had failed standard chemotherapy. PATIENTS AND METHODS: Eligible patients had at least one measurable lesion. The starting dose of paclitaxel was 170 mg/m(2) (135 mg/m(2) for patients with prior pelvic radiation) given as a 24-hour continuous intravenous infusion with courses repeated every 3 weeks. Dose escalation to 200 mg/m(2) and de-escalation to 110 mg/m(2) were allowed based on adverse effects. RESULTS: In this trial, 42 assessable patients were initially entered onto the study, and 13 responses were seen; four patients had a complete response, and nine patients had a partial response. The overall response rate was 31%. The primary and dose-limiting toxicity was neutropenia. CONCLUSION: The response rate to paclitaxel exceeds the rates reported using other single agents in nonsquamous carcinoma of the cervix.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Carcinoma/tratamento farmacológico , Paclitaxel/farmacologia , Neoplasias do Colo do Útero/tratamento farmacológico , Adulto , Idoso , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/efeitos adversos , Carcinoma/patologia , Feminino , Humanos , Infusões Intravenosas , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Resultado do Tratamento , Neoplasias do Colo do Útero/patologia
5.
J Clin Oncol ; 17(5): 1339-48, 1999 May.
Artigo em Inglês | MEDLINE | ID: mdl-10334517

RESUMO

PURPOSE: In 1986, a protocol comparing primary radiation therapy (RT) plus hydroxyurea (HU) to irradiation plus fluorouracil (5-FU) and cisplatin (CF) was activated by the Gynecologic Oncology Group (GOG) for the treatment of patients with locally advanced cervical carcinoma. The goals were to determine the superior chemoradiation regimen and to quantitate the relative toxicities. METHODS: All patients had biopsy-proven invasive squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix. Patients underwent standard clinical staging studies and their tumors were found to be International Federation of Gynaecology and Obstetrics stages IIB, III, or IVA. Negative cytologic washings and para-aortic lymph nodes were required for entry. Patients were randomized to receive either standard whole pelvic RT with concurrent 5-FU infusion and bolus CF or the same RT plus oral HU. RESULTS: Of 388 randomized patients, 368 were eligible; 177 were randomized to CF and 191 to HU. Adverse effects were predominantly hematologic or gastrointestinal in both regimens. Severe or life-threatening leukopenia was more common in the HU group (24%) than in the CF group (4%). The difference in progression-free survival (PFS) was statistically significant in favor of the CF group (P = .033). The sites of progression in the two treatment groups were not substantially different. Survival was significantly better for the patients randomized to CF (P = .018). CONCLUSION: This study demonstrates that for patients with locally advanced carcinoma of the cervix, the combination of 5-FU and CF with RT offers patients better PFS and overall survival than HU, and with manageable toxicity.


Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Adenoescamoso/tratamento farmacológico , Carcinoma Adenoescamoso/radioterapia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/radioterapia , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Adenoescamoso/patologia , Carcinoma de Células Escamosas/patologia , Cisplatino/administração & dosagem , Terapia Combinada , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias do Colo do Útero/patologia
6.
Int J Gynecol Pathol ; 17(4): 320-6, 1998 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9785132

RESUMO

Cyclin dependent kinases (cdks) and cyclins regulate the progression of cells through the cell cycle and can be overexpressed in human cancers. The purpose of this study was to evaluate the immunohistochemical profile of these proliferation-associated proteins and correlate the results with clinicopathologic parameters of endometrial carcinomas. Archival tissue sections from 91 endometrial carcinomas were immunostained using monoclonal antibodies against p34CDC2 cdk, cyclins A and B1, p120, Ki-67, and PCNA. Immunoreactivity was semiquantitatively assessed and the results correlated with pathologic features and survival. Of the 91 endometrial carcinomas, 74 were endometrioid (17 villoglandular, 57 of usual type) and 17 were papillary serous carcinomas. The positivity rates for the different proteins in papillary serous and endometrioid tumors, respectively, were as follows: p34CDC2, 24% and 23%; cyclin A, 71% and 64%; cyclin B1, 24% and 26%; p120, 47% and 9%; Ki-67, 82% and 64%; and PCNA, 47% and 47%. Only p120 correlated with histologic tumor type with significantly higher expression in both papillary serous and villoglandular endometrioid carcinomas compared to nonvilloglandular endometrioid carcinomas (p = 0.0001). p120 positivity also correlated with advanced tumor stage (p = 0.0001). Ki-67, cyclin A, and PCNA correlated with patient survival in endometrioid carcinomas on univariate analysis (p = 0.01, 0.02, and 0.003, respectively), but, on multivariate analysis, only tumor grade (p = 0.02) and depth of invasion (p = 0.04) were independent predictors of outcome. In summary, although most of the cell proliferation-associated proteins studied did not appear to be associated with clinicopathologic features of endometrial carcinoma, there was significantly higher expression of p120 in papillary serous and villoglandular endometrioid carcinomas compared to nonvilloglandular endometrioid carcinomas, suggesting a possible role of p120 in tumor behavior. In addition, Ki-67, cyclin A, and PCNA expression correlated with survival in endometrioid carcinoma, but only in a univariate analysis.


Assuntos
Carcinoma Endometrioide/química , Quinases Ciclina-Dependentes/análise , Ciclinas/análise , Cistadenocarcinoma Papilar/química , Neoplasias do Endométrio/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais , Proteína Quinase CDC2/análise , Carcinoma Endometrioide/mortalidade , Carcinoma Endometrioide/patologia , Ciclina A/análise , Ciclina B/análise , Ciclina B1 , Cistadenocarcinoma Papilar/mortalidade , Cistadenocarcinoma Papilar/patologia , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Feminino , Humanos , Imuno-Histoquímica , Antígeno Ki-67/análise , Pessoa de Meia-Idade , Proteínas Nucleares/análise , Antígeno Nuclear de Célula em Proliferação/análise , Taxa de Sobrevida , tRNA Metiltransferases
7.
Am J Clin Oncol ; 21(2): 145-6, 1998 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-9537200

RESUMO

Twenty-six evaluable patients who had leiomyosarcoma of the uterus were treated with amonafide, 300 mg/m2, for 5 consecutive days every 3 weeks. One partial response (4%) resulted. Hematologic toxicity was substantial, with grade 3 or 4 events occurring as follows: leukopenia, 12 patients (46%); thrombocytopenia, 4 patients (15%); and granulocytopenia, 7 patients (27%). One patient had transient grade 4 renal failure. Considering the poor activity and substantial toxicity that was observed, no further studies are planned by the Gynecologic Oncology Group using amonafide at this dose schedule in leiomyosarcomas.


Assuntos
Antineoplásicos/uso terapêutico , Imidas/uso terapêutico , Isoquinolinas/uso terapêutico , Leiomiossarcoma/tratamento farmacológico , Neoplasias Uterinas/tratamento farmacológico , Adenina , Adulto , Idoso , Antineoplásicos/efeitos adversos , Feminino , Humanos , Imidas/efeitos adversos , Isoquinolinas/efeitos adversos , Pessoa de Meia-Idade , Naftalimidas , Organofosfonatos
8.
Gynecol Oncol ; 67(2): 203-7, 1997 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9367709

RESUMO

OBJECTIVE: The aim of this study was to investigate local regional control, survival, and morbidity in patients with FIGO IIB and IIIB squamous cell carcinoma of the cervix treated with primary extended field (prophylactic paraaoratic radiation) radiation and weekly cisplatin. METHODS: Sixty-seven patients (44 IIB and 23 IIIB) with carcinoma of the cervix received cisplatin at 1 mg/kg (up to 60 mg) weekly and extended field radiation therapy including the paraaortic nodes and brachytherapy. RESULTS: After the scheduled therapy 94.1% of the patients were complete responders. Seventy-five percent are alive without evidence of disease with a mean follow-up of 47.5 months. CONCLUSION: This study confirms the ability to give concomitant weekly cisplatin and prophylactic paraaortic radiation with minimal morbidity. The encouraging Kaplan-Meier survival of 75% and only eight pelvic failures warrants further investigation.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/terapia , Cisplatino/uso terapêutico , Neoplasias do Colo do Útero/terapia , Adulto , Idoso , Braquiterapia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Terapia Combinada , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Taxa de Sobrevida , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia
9.
Gynecol Oncol ; 66(2): 258-61, 1997 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9264573

RESUMO

OBJECTIVE: To evaluate a regimen of radiation and chemotherapy as an alternative for those patients in whom the location and extent of advanced vulvar carcinoma make pelvic exenteration the only surgical option. METHODS: Between December 1988 and March 1995, 14 patients with primary squamous carcinoma of the vulva who were not candidates for standard radical vulvectomy were treated with radiation therapy in combination with cisplatin and 5-fluorouracil (5-FU) chemotherapy at the Albany Medical Center. Patients ranged in age from 40 to 90 years, mean 68. Tumors were stage III in 9 patients and stage IV in 5 patients. Treatment included two cycles of chemotherapy with cisplatin (50 mg/m2) and 5-FU (1000 mg/m2/24 x 96 hr) in addition to radiation therapy. Total radiation doses to the vulva and groins ranged from 50 to 65 Gray (Gy), with pelvic doses of 45 to 50 Gy. Surgical excision of the primary site was not performed in patients who had complete clinical response. RESULTS: Acute complications included desquamation requiring treatment interruptions in 5 patients and deep venous thrombosis in 1 patient. Delayed complications were limited to small bowel obstruction and colonic stricture in one patient. There was a 92% response rate with complete responses in 9 patients (64%). Among patients with complete clinical response, there has been only one recurrence with follow-up of 7-81 months, mean 36.5. All patients with partial responses died, with survival of 8-25 months, mean 15.7. CONCLUSIONS: This combination of chemoradiation was found to be effective therapy for locally advanced vulvar carcinoma, with acceptable morbidity even in an elderly population. Surgical excision of the primary site is not necessary in patients with complete response.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Neoplasias Vulvares/tratamento farmacológico , Neoplasias Vulvares/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/administração & dosagem , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Cisplatino/administração & dosagem , Terapia Combinada , Feminino , Fluoruracila/administração & dosagem , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Taxa de Sobrevida , Neoplasias Vulvares/mortalidade , Neoplasias Vulvares/patologia
10.
Mod Pathol ; 10(8): 823-31, 1997 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9267826

RESUMO

Prognostic factors capable of detecting potential for aggressive disease in early stage endometrial cancer might be useful in selecting patients for early adjuvant therapy. Sixty-three patients with surgical Stage I endometrial carcinoma treated by hysterectomy with a mean follow-up of 55 months were evaluated for tumor type, grade, depth of myometrial invasion, presence of vascular invasion, DNA ploidy, and HER-2/neu overexpression by immunohistochemical techniques. These results were compared with HER-2/neu gene amplifications evaluated by fluorescence in situ hybridization (FISH) and their ability to predict disease survival. For FISH, sections 5 microns thick of formalin-fixed, paraffin-embedded tissues were processed using the Oncor Chromosome In Situ Hybridization System. Automated hybridization using the Ventana Gen was performed with the Oncor unique sequence digoxigenin-labeled HER-2/neu DNA probe. Gene copy numbers were evaluated using the Zeiss Axioskop50 fluorescence microscope. HER-2/neu amplification was noted in 24 (38%) of 63 cases. By multivariate analysis, only aneuploidy (P = .04) and HER-2/neu amplification by FISH (P = .04) independently correlated with survival. Although we saw a relationship between HER-2/neu protein expression and gene amplification, this trend did not achieve statistical significance. HER-2/neu oncogene amplification can be assessed using automated FISH on formalin-fixed, paraffin-embedded tissue. HER-2/ neu amplification predicts poor outcome in Stage I endometrial cancer. HER-2/neu amplification status has potential use in the identification of patients with high risk of disease recurrence who might benefit from intensified therapy.


Assuntos
Neoplasias do Endométrio/genética , Amplificação de Genes , Receptor ErbB-2/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Aneuploidia , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/mortalidade , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Receptor ErbB-2/metabolismo , Taxa de Sobrevida
11.
Cancer Res ; 57(13): 2760-4, 1997 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-9205088

RESUMO

Telomerase, a ribonucleoprotein associated with synthesis of telomeric DNA, is postulated to play a role in cellular senescence and immortalization. Telomerase adds a hexonucleotide telomeric sequence to the chromosomal ends during replication and is preferentially expressed in most malignant and germ-line tissues but is usually undetectable in normal somatic cells. In the current study, 34 human endometrial tissues (20 malignant and 14 benign) were analyzed for telomerase activity by a nonradioactive PCR-based method using the TRAP-eze telomeric repeat amplification detection kit (Oncor). Nineteen of 20 (95%) endometrial carcinomas and 8 of 8 (100%) benign endometrial tissues from premenopausal women exhibited strong telomerase activity, whereas 6 of 6 (100%) benign endometrial tissues from postmenopausal women showed only weak telomerase activity. There was no correlation of telomerase activity with tumor grade, depth of invasion, or DNA content. Benign cycling endometrium, a rapidly proliferating tissue, features positive telomerase activity, although expression in nonneoplastic tissues has only rarely been previously reported. Only weak activity is detected in endometrial tissues after menopause, but telomerase activity can be strongly reactivated in patients who develop endometrial cancer.


Assuntos
Neoplasias do Endométrio/enzimologia , Endométrio/enzimologia , Telomerase/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Endométrio/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Estudos Retrospectivos
12.
Mod Pathol ; 10(5): 401-8, 1997 May.
Artigo em Inglês | MEDLINE | ID: mdl-9160302

RESUMO

To assess the recognition of non-neoplastic epithelial alterations of the vulva and to compare terminologies used for these lesions by various specialties, we performed a clinical and dermatopathologic review of all of the cases diagnosed as non-neoplastic epithelial alterations of the vulva that were followed by one gynecologist. Forty-five initial clinical and pathologic diagnoses made by a group of 14 general surgical pathologists during a 15-year period were compared to the diagnoses made by two dermatopathologists at the time of review. Comparison of diagnoses between the three specialties revealed two types of disparities. The first represented differences in nomenclature. Although all parties frequently agreed on a diagnosis of lichen sclerosus, which represented the most frequent histologic diagnosis, the dermatopathologists did not use the term squamous hyperplasia for any case. Of greater significance was the second type of disparity identified, i.e., failure of the gynecologist and general surgical pathologist to identify uncommon dermatoses in eight cases. Concordance in diagnosis among the dermatopathologists was found in 43 of the 45 cases. These findings are consistent with the view that non-neoplastic epithelial alterations of the vulva are the same as elsewhere in the skin and that terms such as vulvar dystrophy or squamous hyperplasia are not meaningful or helpful in identifying or treating vulvar dermatoses. Unfamiliarity with specific dermatoses and the modified appearance of a dermatosis when occurring on the vulva might cause recognition failure by the gynecologist and general surgical pathologist. Entity recognition might be greatly improved if non-neoplastic vulvar lesions are approached as specific dermatoses rather than being labeled as squamous hyperplasias or vulvar dystrophies. Careful histories and physical examinations aid in identifying less common vulvar dermatoses. Referral to a dermatologist/dermatopathologist is indicated when the diagnosis is in doubt or if the response to treatment is poor.


Assuntos
Terminologia como Assunto , Vulva/patologia , Doenças da Vulva/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Dermatite de Contato/diagnóstico , Dermatologia , Epitélio/patologia , Feminino , Cirurgia Geral , Humanos , Hiperplasia/diagnóstico , Líquen Plano/diagnóstico , Líquen Escleroso e Atrófico/diagnóstico , Pessoa de Meia-Idade , Variações Dependentes do Observador , Patologia , Psoríase/diagnóstico , Estudos Retrospectivos
13.
Am J Clin Oncol ; 20(1): 78-80, 1997 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9020294

RESUMO

A Phase II trial of edatrexate in patients with recurrent cervical carcinoma was conducted by the Gynecologic Oncology Group (GOG). Twenty patients were treated with edatrexate at a dose of 80 mg/m2 i.v. weekly for 5 consecutive weeks per cycle. Four patients received an inadequate trial and were inevaluable for response. Among the 16 patients evaluable for response, there were no objective responses: 50% had stable disease, 50% had progressive disease. All 20 patients were evaluable for toxicity, predominantly stomatitis and bone marrow suppression were substantial. Grades 3-4 bone marrow toxicity were observed in eight of 20 (40%) patients, and there were two deaths due to neutropenic sepsis. Fanconi's syndrome, possibly treatment related, was seen in two patients. Edatrexate administered in this dose and schedule has no demonstrated activity and has severe toxicity in patients with previously-treated advanced cervical cancer.


Assuntos
Aminopterina/análogos & derivados , Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Antagonistas do Ácido Fólico/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias do Colo do Útero/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Aminopterina/efeitos adversos , Aminopterina/uso terapêutico , Antineoplásicos/efeitos adversos , Síndrome de Fanconi/etiologia , Feminino , Antagonistas do Ácido Fólico/efeitos adversos , Humanos , Pessoa de Meia-Idade
14.
Int J Gynecol Pathol ; 15(4): 320-5, 1996 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8886879

RESUMO

In a previous report, we observed by light microscopy the extracellular matrix in 51 vulvar squamous carcinomas and found that some tumors has a prominent stromal response in the form of a regional or diffuse zone of extracellular myxoid matrix containing immature collagen and fibroblasts at the tumor-stromal junction. These tumors were associated with clitoral involvement, ulcerative nonexophytic growth pattern, older age groups, poorer survival rate, and more extensive lymph node metastases than when prominent fibromyxoid stromal response (PFSR) was absent. This behavior was demonstrated despite the fact that these tumors were not larger, more deeply invasive, or of higher grade than when PFSR was absent. In the current immunohistochemical study, we examined cytokine, cell adhesion receptor, and tumor suppressor gene expression in 50 vulvar squamous carcinomas using a panel of antibodies to identify any potential role of these proteins in the development of a PFSR. Semiquantification of expression into none, focal (< 25% of cells showing expression), regional (25-50%), and diffuse (> 50%) patterns revealed PFSR to be statistically associated with high CD44, transforming growth factor (TGF) beta 3, and p53 protein expression, but not with fibroblast growth factor, epidermal growth factor, epidermal growth factor receptor, or E-cadherin expression. When expression of CD44 and either stromal or tumor TGF-beta 3 expression was high, i.e., regional or diffuse in distribution, 15 (50%) of 30 cases were associated with PFSR. In contrast, only 1 (7%) of 14 cases was associated with PFSR when expression was high for only one of these two proteins and none of 3 cases was associated with response when expression was low for both proteins (p = 0.005). Furthermore, in cases showing high expression for both TGF-beta 3 and CD44, PFSR was found in 13 (72%) of 18 cases when p53 expression was diffuse compared with 2 (17%) of 12 cases when expression was less (p = 0.01). Since TGF-beta acts mitogenically for fibroblasts and has been shown to be an inhibitor of epithelial cell growth, its high expression in a carcinoma with PFSR would suggest loss of effect on the epithelial component but an intact effect on the stroma. Since CD44 is known to act as a receptor for hyaluronic acid, which is a prominent stromal component and known to play an important role in cell mobility and tumor aggressiveness, its high expression in association with PFSR would suggest a role of CD44 overexpression in altered hyaluronate metabolism with accelerated tumor cell migration and subsequent distal spread. The current study demonstrates that alterations in cytokine and cell adhesion receptor status variably occur in vulvar squamous carcinoma and that such alterations may affect tumor morphology and behavior.


Assuntos
Carcinoma de Células Escamosas/patologia , Citocinas/metabolismo , Genes Supressores de Tumor , Integrinas/metabolismo , Células Estromais/patologia , Neoplasias Vulvares/patologia , Carcinoma de Células Escamosas/metabolismo , Colágeno/metabolismo , Feminino , Fibroblastos/patologia , Expressão Gênica , Humanos , Receptores de Hialuronatos/análise , Imuno-Histoquímica , Prognóstico , Fator de Crescimento Transformador beta/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Neoplasias Vulvares/metabolismo
15.
Gynecol Oncol ; 62(2): 226-9, 1996 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8751554

RESUMO

This is a Phase II groupwide study of the Gynecologic Oncology Group (GOG) to determine the toxicity and efficacy of a combination of ifosfamide and doxorubicin in patients with advanced or metastatic leiomyosarcomas of the uterus who had not received other chemotherapy. Thirty-five women were entered into this study; 1 patient was ineligible (primary not documented), leaving 34 patients treated with ifosfamide, 5.0 g/m2/24 hr, and mesna, 6.0 g/m2/36 hr, by continuous IV infusion preceded by doxorubicin, 50 mg/m2 iv over 15 min. Each course of therapy was repeated every 3 weeks if counts allowed. One patient was inevaluable for response, leaving 34 evaluable for toxicity and 33 evaluable for response of chemotherapy. GOG grade 3 or 4 granulocytopenia occurred in 17 patients (48.6%), 2 patients developed granulocytopenic fever (5.7%), and 1 died of sepsis. Two patients developed grade 3 thrombocytopenia, and 1 died of cardiotoxicity. There were nine partial and one complete responses for an overall response rate of 30.3%; the response duration averaged 4 months. The combination of ifosfamide and doxorubicin is toxic but has moderate activity in patients with advanced or metastatic leiomyosarcoma of the uterus.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leiomiossarcoma/tratamento farmacológico , Neoplasias Uterinas/tratamento farmacológico , Adulto , Idoso , Antibióticos Antineoplásicos/administração & dosagem , Antineoplásicos Alquilantes/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Humanos , Ifosfamida/administração & dosagem , Pessoa de Meia-Idade , Recidiva , Resultado do Tratamento
16.
Am J Clin Oncol ; 19(2): 184-6, 1996 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8610646

RESUMO

Didemnin B (NSC #335319) was administered i.v. to 26 evaluable patients with advanced, persistent, or recurrent squamous cell carcinoma of the cervix at 6.3 mg/m(2) every 28 days until progression of disease. No patient had had prior cytotoxic therapy alone. Some patients (4) were exposed to radiation sensitizers. There was one complete responder (4.5%). Six patients had stable disease (27.3%) and 15 (68.2%) had increasing disease. The toxicities were significant, with 11 patients (42.3%) experiencing grade 3 or 4 adverse effects. Didemnin B, when used with this dose and schedule, has minimal activity in squamous cell carcinoma of the cervix.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Depsipeptídeos , Peptídeos Cíclicos/uso terapêutico , Neoplasias do Colo do Útero/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antieméticos/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Coagulação Sanguínea/efeitos dos fármacos , Progressão da Doença , Esquema de Medicação , Feminino , Humanos , Injeções Intravenosas , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Recidiva Local de Neoplasia/tratamento farmacológico , Peptídeos Cíclicos/administração & dosagem , Peptídeos Cíclicos/efeitos adversos , Radiossensibilizantes/uso terapêutico , Indução de Remissão , Vômito/induzido quimicamente
17.
Int J Gynecol Pathol ; 15(2): 137-45, 1996 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8786203

RESUMO

The frequency, distribution, and significance of a prominent fibromyxoid stromal response to tumor was examined in 51 consecutive cases of invasive squamous carcinoma of the vulva in which the lesion was totally excised and follow-up information available. The stromal response consisted of an admixture of myxoid change and immature collagen with fibroblasts at the tumor-stromal junction and was focally (< 25% of tumor) in 11 of the 51 cases (21%), regionally (26-50% of tumor) in seven cases (14%), diffusely (> 50% of tumor) in eight cases (16%), and not at all in 25 cases (49%). Tumors showing a prominent fibromyxoid stromal response (> 25% of the tumor) were typically flat or elevated ulcerative lesions, whereas carcinomas without a prominent fibromyxoid stromal response were more commonly exophytic. Sixty percent of the tumors with a prominent fibromyxoid stromal response involved the clitoris, compared with clitoral involvement in only 14% of carcinomas without a prominent response. Case showing prominent fibromyxoid stromal response were associated with a significantly older age group, poorer survival rate, and more extensive lymph node metastases than when fibromyxoid stromal response was not prominent. This behavior was manifested despite the fact that these tumors were not larger, more deeply invading, of higher grade, or more likely to show infiltrating patterns of invasion than when fibromyxoid stromal response was not prominent. Because the ability of a tumor to invade is believed to be related in a large part to changes in the relationship of tumor to stroma, a correlation between fibromyxoid stromal response and aggressive tumor behavior would suggest that a specific pattern of alteration in the interaction of tumor cells with stroma occurs in a subset of vulvar squamous carcinomas. The current findings may reflect the diverse etiology of vulvar carcinoma. If the characteristic features of vulvar carcinomas showing a prominent fibromyxoid stromal reaction as shown in this study can be confirmed on larger study populations, "squamous cell carcinomas with prominent fibromyxoid stromal reaction" may be a useful designation for these tumors.


Assuntos
Carcinoma de Células Escamosas/patologia , Matriz Extracelular/patologia , Fibroma/patologia , Neoplasias Vulvares/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/cirurgia , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias Vulvares/mortalidade , Neoplasias Vulvares/cirurgia
18.
Gynecol Oncol ; 60(3): 397-9, 1996 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8774645

RESUMO

During treatment for gynecologic malignancies, many patients require frequent or prolonged intravenous access. Implantable permanent venous access devices are useful in assuring adequate access and improving quality of life. A new technique for central venous access by peripheral placement of a subcutaneous infusion port was evaluated in 18 women undergoing treatment for gynecologic malignancies. Patients were followed prospectively with a mean follow-up of 105 days. Six catheters required removal because of complications, including 1 patient with a catheter site infection and 5 patients (26%) with catheter-related thrombosis. Although the rate of immediate insertion-related complications was low, the incidence of deep venous thrombosis was markedly increased over that reported with other central venous access devices.


Assuntos
Cateterismo Venoso Central , Cateteres de Demora , Neoplasias dos Genitais Femininos/terapia , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Braço/irrigação sanguínea , Cateteres de Demora/efeitos adversos , Feminino , Humanos , Nutrição Parenteral Total , Estudos Prospectivos , Tromboflebite/etiologia
19.
Am J Obstet Gynecol ; 173(6): 1829-34, 1995 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8610771

RESUMO

OBJECTIVE: We previously described vascular invasion-associated changes, defined as the presence of vascular invasion or perivascular lymphocytic infiltrates, as key prognostic indicators in stage I endometrioid carcinoma. The current study was undertaken to examine the prognostic value of HER-2/neu expression in relation to other factors, including vascular invasion-associated changes, in surgical stage I endometrioid carcinoma. STUDY DESIGN: Seventy-one patients with surgical stage I endometrioid carcinoma treated by hysterectomy and followed up were randomly chosen for retrospective analysis of prognostic indicators including standard clincopathologic features, deoxyribonucleic acid ploidy, and HER-2/neu expression. The latter was examined by an objective computerized quantitative immunohistochemical system. RESULTS: By univariate analysis many factors were found to correlate with outcome, including age, tumor grade, depth of invasion, ploidy, HER-2/neu expression, and vascular invasion-associated changes. By multivariate analysis only vascular invasion-associated changes, aneuploidy, and HER-2/neu overexpression were found to independently correlate with survival. Stratification of patients on the basis of these three features revealed survival rates of 100%, 92%, and 60% when none, one, and two or three features were present, respectively. CONCLUSION: This study suggests that HER-2/neu expression correlated with outcome independent of other factors in endometrial carcinoma and may aid in estimating prognosis. The prognostic value of HER-2/neu overexpression independent of vascular invasion suggests that this factor may operate by increasing the ability of tumor cells to grow at a distal site once vascular invasion occurs.


Assuntos
Carcinoma/química , Carcinoma/patologia , Neoplasias do Endométrio/química , Neoplasias do Endométrio/patologia , Proteínas de Neoplasias/análise , Receptor ErbB-2/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/genética , Carcinoma/terapia , Terapia Combinada , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/terapia , Feminino , Humanos , Histerectomia , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Ploidias , Prognóstico , Radioterapia Adjuvante , Distribuição Aleatória , Estudos Retrospectivos , Análise de Sobrevida
20.
Am J Clin Oncol ; 18(6): 495-7, 1995 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8526192

RESUMO

A Phase II trial of gallium nitrate for patients with recurrent or metastatic nonsquamous cell carcinoma of the cervix was conducted by the Gynecologic Oncology Group (GOG) from March 1988 to January 1992. Twenty-six evaluable patients were treated with 750 mg/m2 of gallium nitrate every 3 weeks. Age range was 30-74 years with a median of 48 years. GOG performance status was 0-1 for all but four patients. Two patients had a complete response (7.7%), 1 patient had a partial response (3.8%), 13 patients had stable disease (50.0%), and 10 (38.5%) had increasing disease. The 95% confidence interval for response is 2.4-30.2%. The major toxicities were nausea, vomiting, and anemia. Gallium nitrate has modest activity in patients with nonsquamous cell carcinoma of the cervix.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Gálio/uso terapêutico , Neoplasias do Colo do Útero/tratamento farmacológico , Adenocarcinoma/patologia , Adulto , Idoso , Anemia/induzido quimicamente , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Esquema de Medicação , Feminino , Gálio/administração & dosagem , Gálio/efeitos adversos , Humanos , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Metástase Neoplásica , Indução de Remissão , Estados Unidos , Neoplasias do Colo do Útero/patologia , Vômito/induzido quimicamente
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