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1.
Oncologist ; 23(1): 2-e5, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29158365

RESUMO

LESSONS LEARNED: Colorectal cancers exhibit a high level of cyclooxygenase-2 (COX-2) expression with strong preclinical rationale for improved clinical outcomes with COX-2 inhibition. Celecoxib is a COX-2 inhibitor and we have shown that it can be safely combined with capecitabine and oxaliplatin as part of neoadjuvant treatment with radiation therapy (RT) in rectal cancer.There was a significant improvement in skin toxicity with this combination as compared with historical data. Considering the field has moved on to single-agent capecitabine, we believe future trials with capecitabine and celecoxib hold potential. BACKGROUND: Improved survival is seen among patients with rectal cancer who achieve pathologic complete response (pCR) after neoadjuvant therapy. Cyclooxygenase-2 (COX-2) expression is increased in gastrointestinal malignancies and it may serve as a target to enhance pathologic response. A trial combining chemoradiation and COX-2 inhibition was conducted to evaluate the pCR rate, surgical outcomes, survival, and treatment toxicity. METHODS: Patients with resectable (T3-4, N1-2) rectal cancer within 12 cm of the anal verge were included in this phase II clinical trial. The neoadjuvant treatment consisted of capecitabine 850 mg/m2 b.i.d. Monday through Friday for 5 weeks, weekly oxaliplatin 50 mg/m2 intravenous (IV), celecoxib 200 mg b.i.d. daily, along with concurrent 45 gray radiation therapy in 25 fractions. RESULTS: Thirty-two patients were included in the final analysis. The primary endpoint was pCR: 31% (95% confidence interval [CI]: 16%-50%). Secondary endpoints were surgical downstaging (SD): 75% (95% CI: 57%-89%) and sphincter-sparing surgery (SSS): 56% (95% CI: 38%-74%). Common grade >3 toxicities were diarrhea and abnormal liver function tests (9% each). Grade 0 and 1 toxicities included radiation dermatitis (59% and 34%, respectively) and proctitis (63% and 28%, respectively). At 3 years, disease-free survival and overall survival (OS) were 84% (95% CI: 65%-93%) and 94% (95% CI: 77%-98%), respectively. CONCLUSION: Chemoradiation with celecoxib in rectal cancer was well tolerated and demonstrated high rates of pCR, SD, and SSS. Improvement in skin toxicity (34% grade 1 and no grade 3/4) as compared with historical results (43%-78% grade 3/4) seems to be a significant improvement with addition of celecoxib to neoadjuvant chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/mortalidade , Terapia Neoadjuvante/mortalidade , Neoplasias Retais/terapia , Capecitabina/administração & dosagem , Celecoxib/administração & dosagem , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados não Aleatórios como Assunto , Oxaliplatina/administração & dosagem , Prognóstico , Neoplasias Retais/patologia , Taxa de Sobrevida
2.
Clin Gastroenterol Hepatol ; 15(11): 1791-1799, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28579181

RESUMO

BACKGROUND & AIMS: Environmental factors have been identified that affect risk of hepatocellular carcinoma (HCC), but little is known about the effects of sex hormones on liver cancer development or outcome. The authors investigated whether menopause hormone therapy (MHT) affects risk, age at onset, or outcome of HCC. METHODS: We performed a case-control study of 234 female patients treated for HCC at a tertiary medical center and with 282 healthy women (controls) from January 1, 2004 through May 31, 2015. We collected detailed information on environmental exposures, ages of menarche and menopause, hysterectomies, and uses of birth control and MHT. We performed multivariable logistic and Cox regression analyses to determine the independent effects of factors associated with women on risk and clinical outcome in HCC. The primary outcomes were effect of MHT on HCC risk, the relationship between MHT with hepatitis virus infection on HCC development, and effect of MHT on age at HCC onset or survival after diagnosis of HCC. RESULTS: The estimated adjusted odds ratio (AOR) for HCC in women who ever used estrogen was 0.53 (95% confidence interval [CI], 0.32-0.88). This association was supported by the older age of HCC onset among estrogen users (mean, 64.5 ± 0.9 years) vs nonusers (mean 59.2 ± 1.1 years; P = .001) and the reduced risk of HCC among long-term users (more than 5 years) (AOR, 0.36; 95% CI, 0.20-0.63). Users of estrogen also had a reduced risk for hepatitis-associated HCC: AOR for users, 4.37 (95% CI, 1.67-11.44) vs AOR for nonusers, 17.60 (95% CI, 3.88-79.83). Estrogen use reduced risk of death from HCC (hazard ratio, 0.55; 95% CI, 0.40-0.77; P = .01). Median overall survival times were 33.5 months for estrogen users (95% CI, 25.7-41.3 months) and 24.1 months for nonusers (95% CI, 19.02-29.30 months; P = .008). CONCLUSION: In a case-control study of women with HCC vs female control subjects at a single center, we associated use of estrogen MHT with reduced risk of HCC and increased overall survival times of patients with HCC. Further studies are needed to determine the benefits of estrogen therapy for women and patients with HCC, and effects of tumor expression of estrogen receptor.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/epidemiologia , Terapia de Reposição de Estrogênios/métodos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/epidemiologia , Adulto , Idoso , Carcinoma Hepatocelular/mortalidade , Estudos de Casos e Controles , Feminino , Humanos , Incidência , Neoplasias Hepáticas/mortalidade , Pessoa de Meia-Idade , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento
3.
Cancer ; 119(18): 3334-42, 2013 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-23821538

RESUMO

BACKGROUND: The purpose of this study was to evaluate the factors associated with response rate, resectability, and survival after cisplatin/interferon α-2b/doxorubicin/5-fluorouracil (PIAF) combination therapy in patients with initially unresectable hepatocellular carcinoma. METHODS: The study included 2 groups of patients treated with conventional high-dose PIAF (n = 84) between 1994 and 2003 and those without hepatitis or cirrhosis treated with modified PIAF (n = 33) between 2003 and 2012. Tolerance of chemotherapy, best radiographic response, rate of conversion to curative surgery, and overall survival were analyzed and compared between the 2 groups, and multivariate and logistic regression analyses were applied to identify predictors of response and survival. RESULTS: The modified PIAF group had a higher median number of PIAF cycles (4 versus 2, P = .049), higher objective response rate (36% versus 15%, P = .013), higher rate of conversion to curative surgery (33% versus 10%, P = .004), and longer median overall survival (21.3 versus 10.6 months, P = .002). Multivariate analyses confirmed that positive hepatitis B serology (hazard ratio [HR] = 1.68; 95% confidence interval [CI] = 1.08-2.59) and Eastern Cooperative Oncology Group performance status ≥ 2 (HR = 1.75; 95% CI = 1.04-2.93) were associated with worse survival whereas curative surgical resection after PIAF treatment (HR = 0.15; 95% CI = 0.07-0.35) was associated with improved survival. CONCLUSIONS: In patients with initially unresectable hepatocellular carcinoma, the modified PIAF regimen in patients with no hepatitis or cirrhosis is associated with improved response, resectability, and survival.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Hepatocelular/cirurgia , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Cisplatino/uso terapêutico , Ensaios Clínicos Fase II como Assunto , Estudos de Coortes , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Interferon-alfa/efeitos adversos , Neoplasias Hepáticas/cirurgia , Pessoa de Meia-Idade , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Estudos Retrospectivos , Análise de Sobrevida , Adulto Jovem
4.
Mol Carcinog ; 52 Suppl 1: E139-47, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23776098

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is an emerging epidemic with high prevalence in Western countries. Genome-wide association studies had reported that a variation in the patatin-like phospholipase domain containing 3 (PNPLA3) gene is associated with high susceptibility to NAFLD. However, the relationship between this variation and hepatocellular carcinoma (HCC) has not been well established. We investigated the impact of PNPLA3 genetic variation (rs738409: C>G) on HCC risk and prognosis in the United States by conducting a case-control study that included 257 newly diagnosed and pathologically confirmed Caucasian patients with HCC (cases) and 494 healthy controls. Multivariate logistics and Cox regression models were used to control for the confounding effects of HCC risk and prognostic factors. We observed higher risk of HCC for subjects with a homozygous GG genotype than for those with CC or CG genotypes, the adjusted odds ratio (OR) was 3.21 (95% confidence interval [CI], 1.68-6.41). We observed risk modification among individuals with diabetes mellitus (OR = 19.11; 95% CI, 5.13-71.20). The PNPLA3 GG genotype was significantly associated with underlying cirrhosis in HCC patients (OR = 2.48; 95% CI, 1.05-5.87). Moreover, GG allele represents an independent risk factor for death. The adjusted hazard ratio of the GG genotype was 2.11 (95% CI, 1.26-3.52) compared with CC and CG genotypes. PNPLA3 genetic variation (rs738409: C>G) may determine individual susceptibility to HCC development and poor prognosis. Further experimental investigations are necessary for thorough assessment of the hepatocarcinogenic role of PNPLA3.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/etiologia , Lipase/genética , Cirrose Hepática/etiologia , Neoplasias Hepáticas/etiologia , Proteínas de Membrana/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Cirrose Hepática/mortalidade , Cirrose Hepática/patologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Prognóstico , Estudos Prospectivos , Fatores de Risco , Taxa de Sobrevida , Estados Unidos
5.
Oncologist ; 17(7): 937-46, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22622147

RESUMO

BACKGROUND: Capecitabine administered for 7 days biweekly with oxaliplatin (XELOX) biweekly has been reported to have activity and safety profiles similar to those of standard capecitabine given for 14 days triweekly. Multiple studies have shown that the addition of bevacizumab to 5-fluorouracil-based chemotherapy is active and well tolerated. METHODS: Patients with metastatic colorectal cancer (mCRC) were randomized to XELOX plus bevacizumab using a standard triweekly cycle (Q3W) or a dose-dense biweekly cycle (Q2W) schedule. The primary endpoint was the progression-free survival (PFS) interval. This trial is registered on ClinicalTrials.gov (identifier, NCT00159432). RESULTS: In total, 435 U.S. patients were randomized. The median PFS intervals were 9.6 months in the Q3W group and 9.1 months in the Q2W group. The median overall survival times were 28.4 months and 22.1 months and the median times to treatment failure were 5.5 months and 3.4 months, respectively. Overall, gastrointestinal disorders were the most common (93%) adverse event (AE). Grade 3 or 4 AEs occurred in 75% and 81% of patients in the Q3W and Q2W groups, respectively. Treatment discontinuation as a result of diarrhea (5% versus 10%) and hand-foot syndrome (2% versus 9%) was less common in the Q3W group than in the Q2W group, respectively. CONCLUSIONS: Based on these results, the first-line treatment of U.S. patients with mCRC using a biweekly combination of XELOX and bevacizumab at the doses studied cannot be recommended. XELOX Q3W remains the preferred schedule for the management of mCRC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab , Capecitabina , Neoplasias Colorretais/patologia , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Fluoruracila/análogos & derivados , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina , Estudos Prospectivos
6.
Hepatology ; 49(5): 1563-70, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19399911

RESUMO

Thyroid hormones play an essential role in lipid mobilization, lipid degradation, and fatty acid oxidation. Hypothyroidism has been associated with nonalcoholic steatohepatitis; however, the association between thyroid diseases and hepatocellular carcinoma (HCC) in men and women has not been well established. We investigated the association between hypothyroidism and HCC risk in men and women in a case-control study, which included 420 eligible patients with HCC and 1104 healthy controls. We used multivariate unconditional logistic regression models to control for the confounding effects of established HCC risk factors. A long-term history of hypothyroidism (>10 years) was associated with a statistically significant high risk of HCC in women; after adjusting for demographic factors, diabetes, hepatitis, alcohol consumption, cigarette smoking, and family history of cancer, the odds ratio (OR) was 2.9 (95% confidence interval [CI], 1.3-6.3). Restricted analyses among hepatitis virus-negative subjects, nondrinkers, nondiabetics, nonsmokers, and nonobese individuals indicated a significant association between hypothyroidism and HCC, with an approximate two-fold to three-fold increased risk of HCC development. We observed risk modification among women with diabetes mellitus (OR = 9.4; 95% CI = 2.7-32.7) and chronic hepatitis virus infection (OR = 31.2; 95% CI = 6.3-153.2). A history of hyperthyroidism was not significantly related to HCC (OR = 1.7; CI = 0.6-5.1). We noted significant elevated risk association between hypothyroidism and HCC in women that was independent of established HCC risk factors. Experimental investigations are necessary for thorough assessment of the relationship between thyroid disorders and HCC.


Assuntos
Carcinoma Hepatocelular/epidemiologia , Hipotireoidismo/epidemiologia , Neoplasias Hepáticas/epidemiologia , Adulto , Idoso , Consumo de Bebidas Alcoólicas/efeitos adversos , Carcinoma Hepatocelular/etiologia , Estudos de Casos e Controles , Complicações do Diabetes/epidemiologia , Feminino , Hepatite B Crônica/complicações , Hepatite B Crônica/epidemiologia , Hepatite C Crônica/complicações , Hepatite C Crônica/epidemiologia , Humanos , Hipotireoidismo/complicações , Neoplasias Hepáticas/etiologia , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/epidemiologia , Estados Unidos/epidemiologia
7.
Int J Cancer ; 123(8): 1883-91, 2008 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-18688864

RESUMO

The International Agency for Research on Cancer has declared smoking to be a risk factor for hepatocellular carcinoma (HCC). However, passive exposure to cigarette smoke and use of noncigarette tobacco products on the risk of HCC has not been examined. Therefore, we evaluated the independent effects of different types of smoking exposure along with multiple risk factors for HCC and determined whether the magnitude of smoking was modified by other risk factors in men and women. We conducted a case-control study at The University of Texas M. D. Anderson Cancer Center where 319 HCC patients and 1,061 healthy control subjects were personally interviewed for several HCC risk factors. Multivariate logistic regression analysis was performed to estimate the adjusted odds ratio (AOR) and 95% confidence interval (CI) for each potential risk factor. Use of smokeless tobacco (chewing tobacco and snuff), cigars, pipes and passive smoking exposure were not related to HCC among noncigarette smokers. However, regular cigarette smoking was associated with HCC in men: AOR, 1.9 (95% CI, 1.1-3.1). Heavy alcohol consumption was associated with HCC in women: AOR, 7.7 (95% CI, 2.3-25.1). Cigarette smoking interacted synergistically with chronic infection of hepatitis C virus in men: AOR, 136.3 (95% CI, 43.2-429.6) and with heavy alcohol consumption in women: AOR, 13.7 (95% CI, 3.2-57.9). We conclude that sex differences were observed in HCC relationship with cigarette smoking and alcohol consumption. Controlling for smoking exposure might be a prudent approach to the prevention of HCC, especially in patients with chronic viral hepatitis infections.


Assuntos
Carcinoma Hepatocelular/epidemiologia , Hepatite C Crônica/epidemiologia , Neoplasias Hepáticas/epidemiologia , Fumar/efeitos adversos , Poluição por Fumaça de Tabaco/efeitos adversos , Adulto , Idoso , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/virologia , Estudos de Casos e Controles , Cocarcinogênese , Feminino , Hepatite C Crônica/complicações , Humanos , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Fatores Sexuais , Estados Unidos/epidemiologia
8.
Cancer Med ; 6(9): 2042-2051, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28801995

RESUMO

Hepatocellular Carcinoma (HCC) incidence is increasing in the USA. Gemcitabine (G) and oxaliplatin (O) are active in HCC and biliary duct cancer (BDC). Erlotinib (E) is an EGFR tyrosine kinase inhibitor (TKI) with known activity against both. We sought to evaluate the efficacy of the combination G+O+E. Patients with either of the two diagnosis were treated in a phase II trial. Simons 2 stage design was used. A disease-control rate (DCR), complete response (CR) + partial response (PR)+ stable disease (SD) at 24 weeks of ≤20% and >40% (P0 and P1 of 0.2 and 0.4, respectively) were set as undesirable (null) and desirable results. 26 HCC and 7 BDC patients were accrued. In HCC, 1 PR, 10 SD, and 9 PDs were seen. DCR in HCC was 42%. Among seven (7) patients with BDC, one patient was not evaluable; one achieved a long lasting PR, and five patients had SD and DCR was 86%. Median overall survival (OS) times and progression-free survivals (PFS) were 196 and 149 days in HCC and 238 days and not reached in BDC. PFS at 26 weeks in HCC was 41% and at 21 weeks in BDC was 60%. Grade 3 toxicities in >5% of patients were fatigue (12.9%), neutropenia (9.6%), thrombocytopenia (9.6%), and diarrhea (6.4%). G+O+E exceeded both preset P0a and P1 of the primary objective with a PFS of 41% at 26 weeks for HCC and preliminary BDC data may warrant further investigations.


Assuntos
Neoplasias dos Ductos Biliares/tratamento farmacológico , Carcinoma Hepatocelular/tratamento farmacológico , Desoxicitidina/análogos & derivados , Cloridrato de Erlotinib/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , Compostos Organoplatínicos/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Cloridrato de Erlotinib/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina , Estudos Prospectivos , Análise de Sobrevida , Resultado do Tratamento , Gencitabina
9.
J Clin Oncol ; 21(3): 421-7, 2003 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-12560429

RESUMO

PURPOSE: Because cirrhosis is extremely common in hepatocellular carcinoma (HCC) in the United States, and it precludes the use of several chemotherapy agents, this phase II trial of fluorouracil (FU) and recombinant interferon alfa-2b (rIFNalpha2b) in HCC was launched with the assumption that it could be tolerated by cirrhotics. PATIENTS AND METHODS: Forty-three patients with HCC (34), and fibrolamellar HCC (FLHCC; nine) were treated with continuous intravenous (IV) FU (200 mg/m2/d x 21 every 28 days) and subcutaneous (SC) rIFNalpha2b (4 million U/m2) three times weekly. Survival was determined in all 43 patients, and response could be assessed in 28 HCC and 8 FLHCC patients. RESULTS: The median ages of the patients were 63.5 and 19 years among HCC and FLHCC patients, respectively. Liver cirrhosis was present among 71% of HCC patients but among none of the FLHCC patients. Nine of 36 (25%; four of 28 [14%] HCC patients; five of eight [62.5%] FLHCC patients) patients in which a response could be assessed had a complete response (CR; one patient with FLHCC and no patients with HCC) or partial response (PR; eight patients [four HCC and four FLHCC patients]). Four HCC patients underwent resection, and two had a histologic CR; one HCC patient with a PR underwent orthotopic liver transplantation. One FLHCC patient also underwent resection without clear margins. Overall median survival was 19.5 months (95% confidence interval [CI], 11.2 to 27.8 months); median survival was 15.5 months (95% CI, 8.5 to 22.5 months) among HCC patients, and that of FLHCC patients was 23.1 months (95% CI, 10.3 to 35.9 months). Overall grade 3 or 4 toxicity included stomatitis (32.6%), fatigue (4.7%), and hematologic toxicity (9.3%). CONCLUSION: Continuous IV FU and thrice-weekly SC rIFNalpha2b are an effective treatment, especially for FLHCC, and may have a neoadjuvant role in this disease. This regimen has activity in HCC and can be tolerated even by cirrhotic patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Cirrose Hepática/complicações , Neoplasias Hepáticas/tratamento farmacológico , Adolescente , Adulto , Idoso , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/patologia , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Humanos , Infusões Intravenosas , Injeções Subcutâneas , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/patologia , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Proteínas Recombinantes , Análise de Sobrevida
10.
Liver Cancer ; 4(1): 70-83, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26020030

RESUMO

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) incidence is expected to rise dramatically over the next decades because of increasing hepatitis C infections and obesity-related comorbidities. However, little information exists regarding the treatment of patients with HCC in the community setting. The purpose of this article was to characterize patterns of diagnosis, treatment, and survival for HCC in the community. METHODS: We identified 946 HCC patients in the 2007 National Cancer Institute's Patterns of Care study. Chi-square analyses and multivariable regression were used to examine patient and provider factors associated with treatment and survival by stage at diagnosis. RESULTS: Our primary findings indicate that liver transplants, embolization, or radiofrequency ablation for Barcelona Clinic Liver Cancer stage A patients were performed significantly less often for non-Hispanic blacks, Hispanics, patients in the highest income quartile, and patients with Medicaid. Patients with stage D disease were less likely to receive cancer therapy if they had Medicaid insurance compared to private insurance (p<0.001 for all). In multivariable analyses, all-cause mortality was associated with treatment in a hospital without a residency training program (hazard ratio [HR] 1.4 [1.1,1.9]), more advanced stage (HR: 10.6 [5.7, 19.5] stage D vs. A), and lack of appropriate treatment (HR: 2.4 [1.9,3.2]). CONCLUSIONS: This is the first population-based study to evaluate therapy provided for HCC in the community. Current therapy depended on patients' HCC stage at diagnosis and other clinical and demographic factors. Overall, our study identifies those least likely to receive specific therapies in a variety of health care settings and can inform strategies for promoting appropriate therapy now and as new agents are developed.

11.
Cancer Chemother Pharmacol ; 66(2): 287-94, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19855966

RESUMO

PURPOSE: Imexon is an aziridine-derived iminopyrrolidone which has synergy with gemcitabine in pancreatic cancer cell lines. Gemcitabine is a standard therapy for pancreatic cancer. We performed a phase I trial of imexon and gemcitabine to evaluate safety, dose-limiting toxicity (DLT), and maximum tolerated dose (MTD) in patients with advanced pancreatic cancer. METHODS: Patients with untreated locally advanced or metastatic pancreatic adenocarcinoma received therapy in sequential cohorts on regimen A (n = 19; imexon 200 or 280 mg/m(2) intravenously (IV) over 30 min days 1-5, 15-19 and gemcitabine 800 or 1,000 mg/m(2) IV over 30 min on days 1,8,15 every 28 days) or regimen B (n = 86; imexon 280-1,300 mg/m(2) IV over 30-60 min days 1, 8, and 15 and gemcitabine 1,000 mg/m(2) IV over 30 min on days 1, 8, and 15 every 28 days). RESULTS: One hundred five patients received 340 treatment cycles (median 2, range 1-16). PATIENT CHARACTERISTICS: median age 63, 61% male, ECOG PS 0/1 50%/50%, 93% metastatic. DLT was abdominal cramping and pain, often with transient, acute diarrhea. Best response was confirmed partial response (PR) in 11.4%, 8.9% unconfirmed PR, and 48.1% with stable disease. There was a dose proportional increase in imexon AUC across the doses tested with terminal half life 69 min at the MTD and no alteration of gemcitabine pharmacokinetics. CONCLUSIONS: The recommended phase II dose of imexon is 875 mg/m(2) with gemcitabine 1,000 mg/m(2). DLT was acute abdominal pain and cramping. Encouraging antitumor responses support further evaluation of this combination in advanced pancreatic cancer.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Área Sob a Curva , Estudos de Coortes , Cistina/sangue , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Relação Dose-Resposta a Droga , Feminino , Meia-Vida , Hexanonas/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia , Compostos de Sulfidrila/metabolismo , Tomografia Computadorizada por Raios X , Gencitabina
12.
J Hepatol ; 50(2): 334-41, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19070394

RESUMO

BACKGROUND/AIMS: The study aimed at addressing the connection between positive family history of liver cancer and hepatocellular carcinoma (HCC) development in the USA. METHODS: At The University of Texas M.D. Anderson Cancer Center, 347 patients with pathologically confirmed HCC and 1075 healthy controls were studied. All subjects were interviewed for their family history of cancer, including the number of relatives with cancer, the type of cancer, the individual's relationship with the relative, and the age at which the relative was diagnosed. RESULTS: Independently of hepatitis B virus (HBV) and hepatitis C virus (HCV), a history of liver cancer in first degree relatives was significantly associated with HCC development (AOR=4.1 [95% CI, 1.3-12.9]). Multiple relatives with liver cancer were only observed among HCC patients with chronic HBV/HCV infection. Affected siblings with liver cancer is significantly associated with HCC development with and without HBV/HCV infection; (AOR=5.7 [95% CI, 1.2-27.3]) and (AOR=4.3 [95% CI, 1.01-20.9]), respectively. Individuals with HBV/HCV and a family history of liver cancer were at higher risk for HCC (AOR=61.9 [95% CI, 6.6-579.7]). CONCLUSIONS: First degree family history of liver cancer is associated with HCC development in the USA. Further research exploring the genetic-environment interactions associated with risk of HCC is warranted.


Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Adulto , Idoso , Carcinoma Hepatocelular/etiologia , Estudos de Casos e Controles , Feminino , Hepatite B/complicações , Hepatite C/complicações , Humanos , Neoplasias Hepáticas/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Estados Unidos
13.
J Cancer Res Clin Oncol ; 134(12): 1325-35, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18504614

RESUMO

PURPOSE: Preclinical models showed TAC-101 (4-[3,5-bis(trimethylsilyl) benzamide] benzoic acid), an oral synthetic retinoid, has anti-tumor activity in hepatocellular carcinoma (HCC). A phase I/II study was performed in advanced HCC patients (pts). PATIENTS AND METHODS: Thirty-three patients were enrolled. During Phase I, pts received 40 mg daily for 14 days q3 weeks; 2 of 5 patients developed DLT so dose was reduced to 20 mg/day. Twenty-eight patients received 20 mg/day. RESULTS: No pt had a CR or PR, but 12 of 21 (57%) had SD. Two pts (9.5%) had late PR after discontinuing TAC-101. Median survival (MS) for all 28 pts treated with 20 mg/day was 12.7 months (95% CI 8.8-22.7); MS for 21 evaluable pts was 19.2 months (95% CI 10.4-27.6). CONCLUSIONS: 20 mg of TAC- was well tolerated. Significant disease stabilization (12/21 pts, 57%), 2 late PRs, and prolonged MS (19.2 months) suggest that TAC-101 provides meaningful patient benefit.


Assuntos
Benzoatos/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Retinoides/administração & dosagem , Compostos de Trimetilsilil/administração & dosagem , Administração Oral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Benzoatos/farmacocinética , Carcinoma Hepatocelular/secundário , Feminino , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Metástase Linfática , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Prognóstico , Retinoides/farmacocinética , Taxa de Sobrevida , Distribuição Tecidual , Compostos de Trimetilsilil/farmacocinética , Adulto Jovem
14.
Am J Gastroenterol ; 102(5): 1016-21, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17324130

RESUMO

BACKGROUND: The risk factors for cholangiocarcinoma are poorly defined in the United States. We evaluated hepatitis C virus (HCV), hepatitis B virus (HBV), and liver cirrhosis as risk factors for intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC). METHODS: A case-control study in which cases were cholangiocarcinoma patients referred to the M.D. Anderson Cancer Center between 1992 and 2002 and controls were healthy individuals. Information about liver diseases, family history, diabetes, smoking, and alcohol consumption were collected on both groups. Blood from all participants was tested for HBV and HCV markers. RESULTS: We identified 246 cases (83 ICC and 163 ECC) and matched them to 236 controls. Compared with controls, ICC patients had a higher prevalence of anti-HCV antibodies (6.0%vs 0.8%, P=0.01), anti-HBc (9.6%vs 0%, P<0.0001), and heavy alcohol consumption (21.7%vs 3.8%, P<0.0001). The adjusted odds ratio and 95% confidence interval (CI) were 7.9 (95% CI 1.3-84.5), 28.6 (95% CI 3.9-1,268.1), and 5.9 (95% CI 2.1-17.4), respectively. Only heavy alcohol consumption was higher in patients with ECC than in controls (17.8%vs 3.8%, P=0.003). The prevalence of diabetes and smoking were not significantly different between cases (ICC or ECC) and controls. The prevalence of cirrhosis was higher in patients with ICC than those with ECC (24.1%vs 4.9%, P<0.0001). CONCLUSIONS: Liver cirrhosis and chronic HCV infection are possible risk factors for ICC but not ECC. Heavy alcohol consumption is a risk factor for both ICC and ECC.


Assuntos
Neoplasias dos Ductos Biliares/etiologia , Ductos Biliares Extra-Hepáticos , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/etiologia , Hepatite B/complicações , Hepatite C/complicações , Cirrose Hepática/complicações , Consumo de Bebidas Alcoólicas/efeitos adversos , Neoplasias dos Ductos Biliares/virologia , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Colangiocarcinoma/virologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Estatísticas não Paramétricas , Estados Unidos
15.
Am J Clin Oncol ; 30(4): 350-7, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17762434

RESUMO

BACKGROUND: Capecitabine results in superior response rate, improved safety, and improved convenience compared with 5-fluorouracil (FU)/leucovorin (LV) in metastatic colorectal cancer (MCRC). Irinotecan in combination with 5-FU/LV has been shown to improve efficacy compared with 5-FU/LV alone in MCRC. Therefore, we evaluated the efficacy and safety of capecitabine plus irinotecan every 3 weeks (XELIRI regimen) as first-line treatment. METHODS: Patients with MCRC who were <65 years of age received irinotecan 250 mg/m i.v. on day 1 + capecitabine 1000 mg/m orally twice daily on days 1 to 14, every 3 weeks. Patients >or=65 years of age and those with impaired renal function or with a history of prior radiotherapy received lower doses of both agents (200 mg/m and 750 mg/m twice daily, respectively). RESULTS: A total of 52 patients (29 men, 23 women) were enrolled between October 2001 and August 2003. Median age was 57.5 years (range, 30-79 years); median Karnofsky performance status was 90 (range, 70-100). Treatment led to a response rate of 50% (ITT population) and a disease control rate of 71%. With a median cohort follow-up of 30.5 months, median time to progression and overall survival are 7.8 months (95% confidence interval, 5.6-10.0) and 16.8 months (95% confidence, 11.9 to not reached), respectively. Most common treatment-related grade 3/4 adverse events were neutropenia (25%), diarrhea (20%), vomiting (16%), dehydration (10%), nausea (6%), abdominal pain (6%), and hand-foot syndrome (6%). CONCLUSION: XELIRI is an active first-line treatment of MCRC. Implementation of upfront dose reductions for both agents in patients with risk factors for toxicity appears to have produced a safer regimen compared with previous studies of XELIRI without such dose reductions.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Adulto , Idoso , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Capecitabina , Neoplasias Colorretais/secundário , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/análogos & derivados , Humanos , Irinotecano , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Taxa de Sobrevida , Resultado do Tratamento
16.
Cancer ; 103(4): 749-55, 2005 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-15660400

RESUMO

BACKGROUND: The treatment of patients with hepatocellular carcinoma (HCC) presents a major challenge, because associated cirrhosis limits the choice of chemotherapeutic agents. However, the abundant vascularity of HCC presents an attractive target for antiangiogenic therapy that potentially may be tolerated by cirrhotic patients. The current study was conducted to assess the antitumor activity, treatment tolerance, treatment-related toxicity, and patient survival after the administration of thalidomide in a Phase II trial. METHODS: Thirty-seven HCC patients were accrued between March, 1999, and March, 2000. Initially, the dose of oral thalidomide was escalated from 400 mg per day during the first week to 1000 mg per day by the fifth week, delivering one-third of the dose in the morning and the remaining two-thirds of the dose in the evening prior to bedtime. Changes in the daily drug administration schedule were allowed based on tolerance. Response was assessed at 8-week intervals. RESULTS: Thirty-two of 37 registered patients were evaluable for response. One patient had a partial response (PR), 1 patient had a minor response (MR), 10 patients had stable disease (SD) (31%; 95% confidence interval [95%CI], 16-51%), and 20 patients) (61%; 95%CI, 42-78%) had disease progression. The most commonly encountered toxicity was somnolence, with Grade 3-4 somnolence (>or= 4 hours of sleep during normal waking hours) in 9 patients (35%) and Grade 2 somnolence (800 mg if it was delivered at bedtime. Grade 3-4 skin reactions were observed in 20% of patients, and exfoliative dermatitis was observed in 1 responding patient. The overall median survival was 6.8 months. CONCLUSIONS: With a 5% PR rate, a 5% MR rate, and a 31% SD rate, the results indicate that thalidomide mostly may offer HCC patients disease stabilization. It is possible that, at a different dosage, or combined with other chemotherapy agents, or with the use of a different thalidomide analogue, longer patient survival may be achieved. However, in view of the significant neurologic toxicity encountered among these commonly cirrhotic HCC patients, thalidomide monotherapy at the high doses studied cannot be recommended for the treatment of HCC.


Assuntos
Inibidores da Angiogênese/efeitos adversos , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Talidomida/efeitos adversos , Adulto , Idoso , Carcinoma Hepatocelular/mortalidade , Progressão da Doença , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida
17.
Am J Clin Oncol ; 28(4): 334-9, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16062073

RESUMO

PURPOSE: Exatecan is a hexacyclic topoisomerase-1 inhibitor that has broad in vitro and in vivo activity. A multicenter phase II study to determine the antitumor activity of exatecan was conducted in patients with advanced cholangiocarcinoma and gallbladder carcinoma. METHODS: Patients with 0 to 1 prior chemotherapy regimens, adequate major organ function, and metastatic disease were eligible. Exatecan was administered at a dose of 0.5 mg/m2 IV over 30 minutes daily on days 1 through 5 every 21 days. The primary end point was overall response rate: complete response and partial response (PR). A Simon optimal 2-stage design was employed. Response was assessed every 6 weeks. RESULTS: Forty-two patients were enrolled. Two of 41 evaluated patients (4.9%) had a PR, 4 patients (9.8%) had a minor response, and 12 had stable disease. Twenty patients (51.2%) had progressive disease. The major toxicity was grade 3/4 neutropenia. The median overall survival was 7 months. The 6-month survival rate was 56.1% and the 12-month survival rate was 31.7%. CONCLUSION: Exatecan has minimal activity in advanced biliary tree cancers. Toxicity was predictable and manageable.


Assuntos
Adenocarcinoma/tratamento farmacológico , Neoplasias dos Ductos Biliares/tratamento farmacológico , Ductos Biliares Intra-Hepáticos , Camptotecina/análogos & derivados , Colangiocarcinoma/tratamento farmacológico , Neoplasias da Vesícula Biliar/tratamento farmacológico , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Neoplasias dos Ductos Biliares/mortalidade , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/farmacocinética , Colangiocarcinoma/mortalidade , Esquema de Medicação , Feminino , Neoplasias da Vesícula Biliar/mortalidade , Meia-Vida , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Inibidores da Topoisomerase I , Resultado do Tratamento
18.
Cancer J ; 10(2): 97-103, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15130269

RESUMO

Hepatocellular carcinoma, a common malignancy globally, has been increasing in incidence in the United States, mostly due to the rising incidence of Hepatitis C viral (HCV) infection. The prognosis of patients with this cancer has been poor and even tumor resection has rarely been curative. However, orthotopic liver transplantation (OLT) has been associated with long-term survival benefit and cures, provided rigorous patient-selection criteria were adhered to. Liver cirrhosis is the most common precursor for HCC, and attempts have been made to prevent the progression from liver cirrhosis to HCC. Post resection adjuvant therapies have included interferon, polyprenoic acid, and adoptive immunotherapy. Finding effective systemic treatments for non-resectable HCC has been challenging and quite frustrating. The presence of liver cirrhosis and the associated volume expansion, electrolyte imbalances, decreased liver synthetic and metabolic reserve, and portal hypertension has made the design of systemic therapy for HCC a major challenge. Additionally staging of HCC using the Tumor Node Metastases (TNM) system, but ignoring the underlying liver disease made it extremely difficult to compare results of different trials. However by and large it would seem, that the more aggressive chemotherapy agents and combinations were associated with median survival times of 3-5 months. Considering the vascular nature of HCC it may be reasonable to combine tolerable chemotherapy with newly released agents with angiogenesis inhibiting properties. Thus, systemic therapy of HCC is a work in progress that calls for additional trials of tolerable newer agents and combinations.


Assuntos
Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Animais , Antineoplásicos/uso terapêutico , Vacinas Anticâncer/administração & dosagem , Quimioterapia Adjuvante , Humanos , Interferons/uso terapêutico , Retinoides/uso terapêutico
19.
J Clin Gastroenterol ; 35(3): 266-9, 2002 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12192205

RESUMO

BACKGROUND: the aim of this study was to determine whether hepatitis C virus (HCV) is an underlying cause of the increase in the incidence of hepatocellular carcinoma (HCC) in the United States. STUDY: the medical records of all patients who had received a pathologic diagnosis of HCC at the University of Texas M.D. Anderson Cancer Center, Houston, Texas, U.S.A., during 1993 through 1998 were reviewed. Only patients residing in the United States were analyzed. All patients were tested for HCV and hepatitis B virus serologic markers. RESULTS: the number of patients with HCC referred to M.D. Anderson Cancer Center increased from 143 in 1993 through 1995 to 216 in 1996 through 1998. Twenty-six patients (18%) and 66 patients (31%) with anti-HCV antibodies were diagnosed with HCC from 1993 to 1995 and from 1996 to 1998, respectively, thus constituting a significant increase ( = 0.01). Although the age distribution of these patients did not differ significantly between 1993 to 1995 and 1996 to 1998, the increase in HCV-associated HCC was greatest among patients 40 to 49 years old. Hepatitis B surface antigens (HBsAg) or anti-hepatitis B core antigens were found in 37 patients (26%) with HCC during 1993 to 1995 and in 37 patients (17%) with HCC during 1996 to 1998 ( = 0.06). Moreover, a significant decrease in the prevalence of HBsAg from 1996 to 1998 (21 patients; 10%) compared with 1993 to 1995 (25 patients; 18%) was observed ( = 0.03). CONCLUSION: hepatitis C infection is the major viral factor contributing to the increase in HCC incidence observed in this large-scale, single-center United States-based experience.


Assuntos
Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/virologia , Hepatite C/epidemiologia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/virologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Texas/epidemiologia , Estados Unidos/epidemiologia
20.
Hepatology ; 37(5): 1165-71, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12717398

RESUMO

To elucidate the hematopoietic activity of recombinant human interleukin-11 (rhIL-11, [Neumega, Cambridge, MA]) in patients with cirrhosis and thrombocytopenia, we administered rhIL-11 at 50 microg/kg/d subcutaneously to 10 patients for 10 days with a 30-day follow-up period. All treated patients (n = 9) experienced a gradual, yet significant increase in their platelet count above the baseline value (P < or =.01) reaching the peak value (median, 93,000/microL; range, 60,000-206,000/microL) at a median of 13 days (range, 6-23 days). Eight patients (89%) had a significant increase of > or =50% over the baseline value (P <.05). Moreover, further increases to > or =60,000/microL, > or =80,000/microL, and > or =100,000/microL were observed in 100%, 78%, and 33% of the patients, respectively. A subsequent decline in platelet count was observed at a median of 19 days (range, 7-26 days) after the occurrence of peak concentration. A significant increase in neutrophil count was also demonstrated starting on the third day of treatment (P < or =.01). Concurrent with an increase in the serum level of fibrinogen, transaminase levels declined significantly during treatment period, while bilirubin levels continued to drop for up to 20 days after the initiation of treatment (P <.05). The most frequent effects were due to plasma volume expansion, including conjunctival redness and edema. In conclusion, rhIL-11 can improve platelet counts in patients with early cirrhosis and these patients could benefit from rhIL-11 treatment. However, given the high frequency of regimen-related toxicity, the use of rhIL-11 in patients with cirrhosis should be administered with caution.


Assuntos
Interleucina-11/administração & dosagem , Cirrose Hepática/complicações , Trombocitopenia/tratamento farmacológico , Adulto , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Feminino , Fibrinogênio/metabolismo , Seguimentos , Hemoglobinas , Humanos , Interleucina-11/efeitos adversos , L-Lactato Desidrogenase/sangue , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Trombocitopenia/etiologia , Resultado do Tratamento
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