279 results on '"Venook AP"'
Search Results
202. Section III: Treatment of Advanced Gastrointestinal Cancers.
- Author
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Hochster HS, O'Reilly EM, Ajani JA, and Venook AP
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- 2007
203. Section I: essentials of ensuring excellence in cancer care.
- Author
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Goldberg RM, Marshall JL, Kachnic LA, and Venook AP
- Published
- 2007
204. Section IV: Significance of Recent Study Results and Future Research Directions in Gastrointestinal Oncology.
- Author
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Goldberg RM, Marshall JL, Ajani JA, Philip PA, O'Reilly EM, and Venook AP
- Published
- 2007
205. Colon cancer.
- Author
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Engstrom PF, Arnoletti JP, Benson AB 3rd, Chen YJ, Choti MA, Cooper HS, Dilawari RA, Early DS, Fakih MG, Fuchs C, Grem JL, Kiel K, Knol JA, Leong LA, Ludwig KA, Martin EW Jr, Rao S, Saltz L, Shibata D, Skibber JM, and Venook AP
- Subjects
- Colonic Neoplasms drug therapy, Colonic Neoplasms pathology, Humans, Neoplasm Metastasis, Neoplasm Staging, Risk Assessment, Colonic Neoplasms therapy
- Published
- 2007
206. An alternative therapy for patients with hepatic impairment?
- Author
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Choo SP and Venook AP
- Subjects
- Antibodies, Monoclonal administration & dosage, Antibodies, Monoclonal adverse effects, Antibodies, Monoclonal, Humanized, Antineoplastic Combined Chemotherapy Protocols adverse effects, Bevacizumab, Cetuximab, Chemical and Drug Induced Liver Injury, Colorectal Neoplasms complications, Humans, Hyperbilirubinemia chemically induced, Liver Neoplasms complications, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Colorectal Neoplasms drug therapy, Hyperbilirubinemia complications, Liver Diseases prevention & control, Liver Neoplasms drug therapy, Liver Neoplasms secondary
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- 2007
- Full Text
- View/download PDF
207. Clinical utility of AFP-L3% measurement in North American patients with HCV-related cirrhosis.
- Author
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Sterling RK, Jeffers L, Gordon F, Sherman M, Venook AP, Reddy KR, Satomura S, and Schwartz ME
- Subjects
- Adult, Aged, Canada, Carcinoma, Hepatocellular pathology, Carcinoma, Hepatocellular virology, Cohort Studies, Double-Blind Method, Hepatitis C, Chronic blood, Hepatitis C, Chronic pathology, Humans, Liver Cirrhosis blood, Liver Cirrhosis pathology, Liver Neoplasms pathology, Liver Neoplasms virology, Middle Aged, Plant Lectins, Predictive Value of Tests, United States, Carcinoma, Hepatocellular blood, Hepatitis C, Chronic complications, Liver Cirrhosis complications, Liver Neoplasms blood, alpha-Fetoproteins metabolism
- Abstract
Background and Aims: Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3%) has been reported to be useful in the early detection of hepatocellular carcinoma (HCC) in Japan. The aim of this prospective study was to compare the clinical utility of AFP-L3% with that of total AFP in North American patients., Methods: Patients with chronic hepatitis (CH) C virus-related cirrhosis from 7 clinical sites were prospectively followed every 3-6 months for 2 yr., Results: Of the 372 patients evaluated, 40 had hepatitis C virus-related HCC at entry and 332 entered the prospective trial. Of the latter, 34 developed HCC and 298 remained free of HCC. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for AFP were 60.8%, 71.1%, 34.4%, and 88.0% with a cutoff of 20 ng/mL and 21.6%, 98.7%, 80.0%, and 83.5% with a cutoff of 200 ng/mL, compared to 36.5%, 91.6%, 51.9%, and 85.3% for AFP-L3% with a cutoff of 10%. In those with an elevated AFP (20-200 ng/mL), AFP-L3% had a specificity of 86.6% and an NPV of 80.7%. Multivariate analysis identified AFP, AFP-L3%, and age as independent predictors of HCC. Elevated AFP-L3% was associated with a lower cumulative HCC-free rate at 2 yr (58.9%) than was AFP (82.0%, P= 0.01)., Conclusions: The incidence of HCC was significantly higher in patients with elevated AFP-L3% than in those with elevated AFP. The high specificity of AFP-L3% persisted among patients with elevated AFP (20-200 ng/mL) and suggests that AFP-L3% has clinical utility in HCV patients with AFP of 20-200 ng/mL.
- Published
- 2007
- Full Text
- View/download PDF
208. Rectal cancer.
- Author
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Engstrom PF, Arnoletti JP, Benson AB 3rd, Chen YJ, Choti MA, Cooper HS, Dilawari RA, Early DS, Fakih MG, Fuchs C, Grem JL, Kiel K, Knol JA, Leong LA, Ludwig KA, Martin EW Jr, Rao S, Saltz L, Shibata D, Skibber JM, and Venook AP
- Subjects
- Humans, Neoplasm Staging, Rectal Neoplasms diagnosis, Rectal Neoplasms surgery, Rectal Neoplasms pathology, Rectal Neoplasms therapy
- Published
- 2007
209. A phase II study of fixed-dose rate gemcitabine plus low-dose cisplatin followed by consolidative chemoradiation for locally advanced pancreatic cancer.
- Author
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Ko AH, Quivey JM, Venook AP, Bergsland EK, Dito E, Schillinger B, and Tempero MA
- Subjects
- Adult, Aged, Aged, 80 and over, Antimetabolites, Antineoplastic administration & dosage, California epidemiology, Cisplatin administration & dosage, Comorbidity, Deoxycytidine administration & dosage, Deoxycytidine analogs & derivatives, Dose-Response Relationship, Drug, Female, Gastrointestinal Diseases epidemiology, Humans, Incidence, Male, Middle Aged, Neoplasm Recurrence, Local prevention & control, Pancreatic Neoplasms surgery, Prognosis, Radiation-Sensitizing Agents administration & dosage, Risk Assessment methods, Risk Factors, Survival Analysis, Survival Rate, Treatment Outcome, Gemcitabine, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Neoplasm Recurrence, Local mortality, Pancreatic Neoplasms mortality, Pancreatic Neoplasms therapy, Radiation Injuries epidemiology, Radiotherapy, Adjuvant mortality
- Abstract
Purpose: The optimal strategy for treating locally advanced pancreatic cancer remains controversial, including the respective roles and timing of chemotherapy and radiation. We conducted a Phase II nonrandomized trial to evaluate sequential chemotherapy followed by chemoradiation in this patient population., Methods and Materials: Chemotherapy naive patients with locally advanced pancreatic adenocarcinoma were treated with fixed-dose rate gemcitabine (1,000 mg/m(2) at 10 mg/m(2)/min) plus cisplatin 20 mg/m(2) on Days 1 and 15 of a 28-day cycle. Those without evidence of extrapancreatic metastases after six cycles of chemotherapy received radiation (5,040 cGy over 28 fractions) with concurrent capecitabine (800 mg/m(2) orally twice daily on the day of radiation) as a radiosensitizer., Results: A total of 25 patients were enrolled with a median follow-up time of 656 days. Twelve patients (48%) successfully received all six cycles of chemotherapy plus chemoradiation. Eight patients (32%) progressed during chemotherapy, including 7 with extrapancreatic metastases. Grade 3/4 hematologic toxicities were uncommon. Two patients sustained myocardial infarctions during chemotherapy, and 4 were hospitalized for infectious complications, although none in the setting of neutropenia. Median time to progression was 10.5 months and median survival was 13.5 months, with an estimated 1-year survival rate of 62%. Patients receiving all components of therapy had a median survival of 17.0 months., Conclusions: A strategy of initial fixed-dose rate gemcitabine-based chemotherapy, followed by chemoradiation, shows promising efficacy for treatment of locally advanced disease. A substantial proportion of patients will be identified early on as having extrapancreatic disease and spared the potential toxicities associated with radiation.
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- 2007
- Full Text
- View/download PDF
210. Systemic and regional nonsurgical therapy--what is the optimal strategy for metastatic neuroendocrine cancer?
- Author
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Nakakura EK, Venook AP, and Bergsland EK
- Subjects
- Antineoplastic Agents therapeutic use, Chemoembolization, Therapeutic, Hepatic Artery, Humans, Liver Neoplasms diagnosis, Liver Neoplasms secondary, Liver Neoplasms therapy, Neoplasm Metastasis, Neuroendocrine Tumors diagnosis, Neuroendocrine Tumors secondary, Neuroendocrine Tumors therapy
- Abstract
A multidisciplinary team is essential for the optimal management of patients with metastatic neuroendocrine tumors. In this article, the systemic and regional nonsurgical therapeutic options for metastatic neuroendocrine cancers are discussed. In particular, the roles of biotherapy, chemotherapy, and hepatic artery embolization/chemoembolization are reviewed. A proposed treatment algorithm is provided with the aim of providing clinicians with a useful framework for managing these challenging patients. Finally, the rationale for promising investigational therapies is described.
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- 2007
- Full Text
- View/download PDF
211. Revisiting the Cancer and Leukemia Group B/Southwest Oncology Group 80405 Trial: a phase III trial of chemotherapy and biologic agents for patients with untreated advanced colorectal adenocarcinoma.
- Author
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Venook AP, Blanke CD, Niedzwiecki D, Lenz HJ, Taylor JR, Hollis DR, Sutherland S, and Goldberg RM
- Subjects
- Adenocarcinoma pathology, Antibodies, Monoclonal administration & dosage, Antibodies, Monoclonal, Humanized, Bevacizumab, Cetuximab, Colorectal Neoplasms pathology, Fluorouracil administration & dosage, Humans, Leucovorin administration & dosage, Neoplasm Staging, Adenocarcinoma drug therapy, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Biological Products therapeutic use, Colorectal Neoplasms drug therapy
- Published
- 2007
- Full Text
- View/download PDF
212. Frequency of hepatic contour abnormalities and signs of portal hypertension at CT in patients receiving chemotherapy for breast cancer metastatic to the liver.
- Author
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Qayyum A, Lee GK, Yeh BM, Allen JN, Venook AP, and Coakley FV
- Subjects
- Adult, Aged, Aged, 80 and over, Breast Neoplasms epidemiology, California epidemiology, Comorbidity, Female, Humans, Hypertension, Portal epidemiology, Incidence, Liver Neoplasms epidemiology, Middle Aged, Retrospective Studies, Risk Assessment methods, Risk Factors, Antineoplastic Agents therapeutic use, Breast Neoplasms diagnostic imaging, Breast Neoplasms drug therapy, Hypertension, Portal diagnostic imaging, Liver Neoplasms diagnostic imaging, Liver Neoplasms secondary, Tomography, X-Ray Computed statistics & numerical data
- Abstract
Purpose: This study aimed to determine the frequency of hepatic contour abnormalities and signs of portal hypertension at serial CT in patients receiving chemotherapy for breast cancer metastatic to the liver., Materials and Methods: We retrospectively identified 91 women with breast cancer metastatic to the liver who received chemotherapy and underwent serial CT at our institution between 1998 and 2002. Two readers independently categorized hepatic contour abnormalities on the final CT examination as none, limited retraction, widespread retraction, or diffuse nodularity. Readers also recorded the development of hepatic atrophy or enlargement, ascites, portosystemic collateral veins, and splenomegaly. Interpretative discrepancies were resolved by consensus. Portal hypertension was defined as the presence of at least two of the following CT signs: simple ascites, portosystemic collateral veins, and splenomegaly., Results: After a median follow-up interval of 15 months (range, 1-46), hepatic contour abnormalities were seen in 68 of 91 patients (75%) and consisted of limited retraction (n = 42), widespread retraction (n = 10), or diffuse nodularity (n = 16). Portal hypertension was found in 1 of 23 patients without contour abnormalities, in 1 of 42 patients with limited retraction, in none of 10 patients with widespread retraction, and in 6 of 16 patients with diffuse nodularity (P < .01)., Conclusion: Hepatic contour abnormalities commonly develop at serial CT in patients undergoing chemotherapy for breast cancer metastatic to the liver and may be accompanied by signs of portal hypertension; the latter are particularly, but not exclusively, associated with the development of diffuse hepatic nodularity.
- Published
- 2007
- Full Text
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213. Chemotherapy and regional therapy of hepatic colorectal metastases: expert consensus statement.
- Author
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Bartlett DL, Berlin J, Lauwers GY, Messersmith WA, Petrelli NJ, and Venook AP
- Subjects
- Antineoplastic Agents administration & dosage, Antineoplastic Agents, Phytogenic administration & dosage, Camptothecin analogs & derivatives, Camptothecin therapeutic use, Chemotherapy, Adjuvant, Hepatic Artery, Humans, Infusions, Intra-Arterial, Irinotecan, Liver Neoplasms drug therapy, Liver Neoplasms surgery, Organoplatinum Compounds therapeutic use, Oxaliplatin, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Colorectal Neoplasms pathology, Hepatectomy, Liver Neoplasms secondary, Liver Neoplasms therapy
- Published
- 2006
- Full Text
- View/download PDF
214. Hepatobiliary cancers. Clinical practice guidelines in oncology.
- Author
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Benson AB 3rd, Bekaii-Saab T, Ben-Josef E, Blumgart L, Clary BM, Curley SA, Davila R, Earle CC, Ensminger WD, Gibbs JF, Laheru D, Langnas AN, Mulvihill SJ, Nemcek AA Jr, Posey JA, Sigurdson ER, Sinanan M, Vauthey JN, Venook AP, Wagman LD, and Yeatman TJ
- Subjects
- Humans, Biliary Tract Neoplasms pathology, Carcinoma, Hepatocellular pathology, Liver Neoplasms pathology
- Published
- 2006
- Full Text
- View/download PDF
215. Phase II study of recombinant human endostatin in patients with advanced neuroendocrine tumors.
- Author
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Kulke MH, Bergsland EK, Ryan DP, Enzinger PC, Lynch TJ, Zhu AX, Meyerhardt JA, Heymach JV, Fogler WE, Sidor C, Michelini A, Kinsella K, Venook AP, and Fuchs CS
- Subjects
- Adult, Aged, Aged, 80 and over, Angiogenesis Inhibitors administration & dosage, Angiogenesis Inhibitors adverse effects, Angiogenesis Inhibitors blood, Antineoplastic Agents administration & dosage, Antineoplastic Agents adverse effects, Antineoplastic Agents blood, Carcinoma, Neuroendocrine blood, Carcinoma, Neuroendocrine pathology, Disease-Free Survival, Endostatins administration & dosage, Endostatins adverse effects, Endostatins blood, Female, Humans, Injections, Subcutaneous, Male, Middle Aged, Recombinant Proteins therapeutic use, Self Administration, Survival Analysis, Treatment Outcome, Angiogenesis Inhibitors therapeutic use, Antineoplastic Agents therapeutic use, Carcinoma, Neuroendocrine drug therapy, Endostatins therapeutic use
- Abstract
Purpose: Endostatin is a 20-kd proteolytic fragment of collagen XVIII that, in preclinical studies, has been shown to have antiangiogenic and antitumor activity. Both preclinical and human phase I studies of recombinant human endostatin (rhEndostatin) suggested activity in neuroendocrine tumors, which are known to be hypervascular. We therefore performed a multicenter phase II study of rhEndostatin in patients with carcinoid or pancreatic neuroendocrine tumors., Patients and Methods: Forty-two patients with advanced pancreatic endocrine tumors or carcinoid tumors were treated with rhEndostatin administered as a bid subcutaneous injection at a starting dose of 60 mg/m2/d. Steady-state trough levels were obtained after 6 weeks of therapy; patients who did not achieve a target therapeutic level of 300 ng/mL underwent dose escalation to 90 mg/m2/d. Patients were observed for evidence of toxicity, response, and survival., Results: rhEndostatin was associated with minimal toxicity. However, among 40 patients assessable for radiologic response, none experienced partial response to therapy, as defined by WHO criteria. The median steady-state trough level achieved after dose escalation was 331 ng/mL, within the postulated therapeutic range., Conclusion: Treatment with rhEndostatin did not result in significant tumor regression in patients with advanced neuroendocrine tumors.
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- 2006
- Full Text
- View/download PDF
216. The cancer and leukemia group B pharmacology and experimental therapeutics committee: a historical perspective.
- Author
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Ratain MJ, Miller AA, McLeod HL, Venook AP, Egorin MJ, and Schilsky RL
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- Clinical Trials as Topic, History, 20th Century, Humans, Leukemia therapy, Pharmacogenetics, Research Design, Societies, Medical history, Antineoplastic Agents pharmacology, Medical Oncology history, Neoplasms therapy
- Abstract
The Chemotherapy Committee of Cancer and Leukemia Group B (CALGB) was established in the mid-1970s to assemble a group of experts in cancer chemotherapy and pharmacology who could advise the CALGB disease committees about the optimal use of drugs in the fight against cancer and to provide quality assurance for the chemotherapy section of CALGB protocols. Chaired initially by Edward Henderson and then David Van Echo, the committee was also the repository of studies in diseases for which CALGB did not have a formal committee, such as testis cancer and sarcoma. In 1990, following the appointment of Richard Schilsky as Chair, the name of the committee was changed to the Pharmacology and Experimental Therapeutics (PET) Committee to reflect a more specific focus and scientific agenda (i.e., studies of chemotherapy pharmacology and development of new agents). Three PET Committee reference pharmacology laboratories (led by Merrill Egorin, Tony Miller, and Mark Ratain) were established to measure drug concentrations in biological fluids and to perform pharmacokinetic analyses. In addition, the PET Committee embarked on a number of multi-institution phase I studies. These phase I studies included studies of special populations, including the first prospective study of an anticancer agent (paclitaxel) in patients with hepatic dysfunction. In addition, the Committee studied a number of phase I combinations destined for phase II evaluation in disease-specific committees. Following Dr. Schilsky's election as CALGB Group Chair in 1994, Mark Ratain took over as Chair of the PET Committee and continued to emphasize population pharmacology as the primary theme of the Committee's research agenda. In addition, the PET Committee began to develop novel clinical trial designs, including the first completed randomized discontinuation trial of an antineoplastic agent. Most recently, the PET Committee has launched an ambitious research program in pharmacogenetics, facilitated in large part through the recruitment of Howard McLeod as Vice Chair. This area of research is a collaborative effort with the NIH Pharmacogenetics Research Network and has the potential to definitively address the hypothesis that germ line polymorphisms are a significant determinant of the toxicity and efficacy of anticancer therapy. It is anticipated that the results of the current studies will contribute significantly to the goal of individualizing cancer treatment.
- Published
- 2006
- Full Text
- View/download PDF
217. Targeted therapy in colorectal cancer.
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Rajpal S and Venook AP
- Subjects
- Antibodies, Monoclonal economics, Antibodies, Monoclonal, Humanized, Antineoplastic Agents economics, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bevacizumab, Cetuximab, Colorectal Neoplasms secondary, ErbB Receptors antagonists & inhibitors, Humans, Vascular Endothelial Growth Factor A antagonists & inhibitors, Antibodies, Monoclonal therapeutic use, Antineoplastic Agents therapeutic use, Colorectal Neoplasms drug therapy
- Abstract
Advances in chemotherapeutic agents have led to improved outcomes for patients with metastatic colorectal cancer (CRC). Chemotherapies, however, are limited by their toxicities and lack of specificity. Aberrations in the regulation and expression of growth factors have been implicated in the development of CRC, and this understanding has led to the development of targeted agents. In 2004, two novel agents, bevacizumab and cetuximab, were approved by the US Food and Drug Administration for the treatment of metastatic CRC. Bevacizumab, a humanized monoclonal antibody to vascular endothelial growth factor, and cetuximab, a human-mouse chimeric monoclonal antibody to the epidermal growth factor receptor, have changed the field dramatically. Bevacizumab appears to augment the efficacy of combination chemotherapy regimens for the treatment of metastatic CRC in both the first- and second-line settings, and the role of bevacizumab as part of adjuvant treatment is the subject of ongoing trials. However, because of the increased incidence of serious arterial thromboembolic events, gastrointestinal perforations, bleeding complications, and hypertension associated with bevacizumab, this agent is probably not indicated in all circumstances. Combination treatment with cetuximab and irinotecan appears appropriate in patients with advanced CRC who have failed irinotecan. Patients who are unable to receive additional irinotecan may be treated with cetuximab monotherapy. Positive epidermal growth factor receptor status by immunohistochemistry of a tumor specimen is presently mandated to determine candidacy for this therapy, although this assay appears to be suboptimal and newer assessment techniques to determine suitability for therapy must be developed. Phase III trials should shed light on the role of cetuximab in the first-line metastatic and adjuvant settings. Multitargeted strategies in CRC combining chemotherapy with bevacizumab and cetuximab are currently being explored. Further advances in the treatment of CRC are expected through continued scientific investigation and well-designed clinical trials.
- Published
- 2006
218. Phase II study of fixed dose rate gemcitabine with cisplatin for metastatic adenocarcinoma of the pancreas.
- Author
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Ko AH, Dito E, Schillinger B, Venook AP, Bergsland EK, and Tempero MA
- Subjects
- Adenocarcinoma ethnology, Adult, Aged, Antimetabolites, Antineoplastic adverse effects, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols adverse effects, CA-19-9 Antigen blood, Cisplatin administration & dosage, Deoxycytidine administration & dosage, Deoxycytidine adverse effects, Disease Progression, Disease-Free Survival, Drug Administration Schedule, Female, Follow-Up Studies, Humans, Male, Middle Aged, Pancreatic Neoplasms ethnology, Research Design, Survival Analysis, Tomography, X-Ray Computed, Treatment Outcome, Gemcitabine, Adenocarcinoma drug therapy, Antimetabolites, Antineoplastic administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Deoxycytidine analogs & derivatives, Pancreatic Neoplasms drug therapy
- Abstract
Purpose: Although gemcitabine remains the standard of care for patients with advanced pancreatic cancer, additional improvements may be realized by combining therapeutic agents with synergistic activity, and optimizing drug delivery using pharmacokinetic principles such as fixed dose rate (FDR) infusion. The objectives of this study were to determine safety and efficacy in patients with metastatic pancreatic cancer treated with FDR gemcitabine in combination with low-dose cisplatin., Patients and Methods: Chemotherapy-naive patients with metastatic pancreatic adenocarcinoma were treated with a combination of gemcitabine 1,000 mg/m2 at 10 mg/m2/min together with cisplatin 20 mg/m2 on days 1 and 8 of a 21-day cycle. Patient follow-up was performed using computerized tomographic scans and serial CA 19-9 measurements., Results: A total of 51 patients were enrolled onto the study, with a median follow-up time of 215 days. Twenty-two of 40 patients (55.0%) with a baseline serum CA 19-9 level > or = 2x the upper limit of normal demonstrated a > or = 50% biomarker decline during treatment. Nine of 47 patients (19.1%) with measurable disease achieved a partial response, and 28 patients (59.6%) had disease stabilization for at least two treatment cycles. Median time to progression was 3.9 months and median survival was 7.1 months, with an estimated 1-year survival rate of 29%. The most frequently reported grade 3 or 4 adverse events were neutropenia (52.9%) and thrombocytopenia (15.7%). Most patients were switched to an every-other-week dosing schedule., Conclusion: The combination of FDR gemcitabine and cisplatin is well tolerated and appears to be an acceptable, albeit not clearly superior, alternative to other gemcitabine/platinum regimens for the treatment of metastatic pancreatic cancer.
- Published
- 2006
- Full Text
- View/download PDF
219. Cancer and Leukemia Group B/Southwest Oncology Group trial 80405: a phase III trial of chemotherapy and biologics for patients with untreated advanced colorectal adenocarcinoma.
- Author
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Venook AP, Blanke CD, Niedzwiecki D, Lenz HJ, Taylor JR, Hollis DR, Sutherland S, and Goldberg RM
- Subjects
- Adenocarcinoma drug therapy, Adenocarcinoma pathology, Adult, Antibodies, Monoclonal therapeutic use, Antibodies, Monoclonal, Humanized, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bevacizumab, Camptothecin analogs & derivatives, Camptothecin therapeutic use, Cetuximab, Colorectal Neoplasms drug therapy, Colorectal Neoplasms pathology, Fluorouracil therapeutic use, Humans, Leucovorin therapeutic use, Neoplasm Staging, Organoplatinum Compounds therapeutic use, Adenocarcinoma therapy, Antineoplastic Agents therapeutic use, Biological Products therapeutic use, Colorectal Neoplasms therapy
- Published
- 2005
- Full Text
- View/download PDF
220. Colon cancer clinical practice guidelines in oncology.
- Author
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Engstrom PF, Benson AB 3rd, Chen YJ, Choti MA, Dilawari RA, Enke CA, Fakih MG, Fuchs C, Kiel K, Knol JA, Leong LA, Ludwig KA, Martin EW Jr, Rao S, Saif MW, Saltz L, Skibber JM, Venook AP, and Yeatman TJ
- Subjects
- Antineoplastic Combined Chemotherapy Protocols, Chemotherapy, Adjuvant, Colectomy, Colonic Neoplasms pathology, Colonic Neoplasms surgery, Colonic Polyps diagnosis, Colonic Polyps therapy, Colostomy, Humans, Liver Neoplasms secondary, Liver Neoplasms surgery, Lung Neoplasms secondary, Lung Neoplasms surgery, Lymph Node Excision, Lymphatic Metastasis, Neoplasm Invasiveness, Neoplasm Staging, Risk Assessment, Salvage Therapy, Colonic Neoplasms diagnosis, Colonic Neoplasms therapy, Medical Oncology standards
- Published
- 2005
- Full Text
- View/download PDF
221. Rectal cancer clinical practice guidelines in oncology.
- Author
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Engstrom PF, Benson AB 3rd, Chen YJ, Choti MA, Dilawari RA, Enke CA, Fakih MG, Fuchs C, Kiel K, Knol JA, Leong LA, Ludwig KA, Martin EW Jr, Rao S, Saif MW, Saltz L, Skibber JM, Venook AP, and Yeatman TJ
- Subjects
- Antineoplastic Combined Chemotherapy Protocols therapeutic use, Camptothecin analogs & derivatives, Camptothecin therapeutic use, Fluorouracil therapeutic use, Humans, Leucovorin therapeutic use, Liver Neoplasms secondary, Lung Neoplasms secondary, Lymphatic Metastasis, Neoplasm Staging, Organoplatinum Compounds therapeutic use, Radiotherapy, Adjuvant, Rectal Neoplasms drug therapy, Rectal Neoplasms radiotherapy, Medical Oncology standards, Rectal Neoplasms diagnosis, Rectal Neoplasms surgery
- Published
- 2005
- Full Text
- View/download PDF
222. Anal canal cancer clinical practice guidelines in oncology.
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Engstrom PF, Benson AB 3rd, Chen YJ, Choti MA, Dilawari RA, Enke CA, Fakih MG, Fuchs C, Kiel K, Knol JA, Leong LA, Ludwig KA, Martin EW Jr, Rao S, Saif MW, Saltz L, Skibber JM, Venook AP, and Yeatman TJ
- Subjects
- Anus Neoplasms diagnosis, Anus Neoplasms pathology, Combined Modality Therapy, Humans, Neoplasm Staging, Anus Neoplasms therapy, Medical Oncology standards
- Published
- 2005
- Full Text
- View/download PDF
223. Epidermal growth factor receptor-targeted treatment for advanced colorectal carcinoma.
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Venook AP
- Subjects
- ErbB Receptors physiology, Humans, Signal Transduction, Antibodies, Monoclonal therapeutic use, Antineoplastic Agents therapeutic use, Colorectal Neoplasms drug therapy, ErbB Receptors antagonists & inhibitors
- Abstract
Substantial effort has focused on the development of novel targeted agents for treating patients with late-stage colorectal carcinoma. These agents are designed specifically to inhibit biochemical processes associated with pathogenesis. Numerous molecules targeting the epidermal growth factor receptor have been investigated as therapeutic agents and appear to herald a shift in the treatment paradigm for colorectal carcinoma., (Copyright 2005 American Cancer Society.)
- Published
- 2005
- Full Text
- View/download PDF
224. Fractional genomic alteration detected by array-based comparative genomic hybridization independently predicts survival after hepatic resection for metastatic colorectal cancer.
- Author
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Mehta KR, Nakao K, Zuraek MB, Ruan DT, Bergsland EK, Venook AP, Moore DH, Tokuyasu TA, Jain AN, Warren RS, Terdiman JP, and Waldman FM
- Subjects
- Aged, Chromosomes, Artificial, Bacterial, DNA, Neoplasm analysis, Female, Genome, Humans, In Situ Hybridization, Liver Neoplasms surgery, Male, Middle Aged, Predictive Value of Tests, Prognosis, Risk Factors, Survival Analysis, Colorectal Neoplasms genetics, Colorectal Neoplasms pathology, Gene Dosage, Gene Expression Profiling, Liver Neoplasms genetics, Liver Neoplasms secondary, Oligonucleotide Array Sequence Analysis
- Abstract
Purpose: Although liver resection is the primary curative therapy for patients with colorectal hepatic metastases, most patients have a recurrence. Identification of molecular markers that predict patients at highest risk for recurrence may help to target further therapy., Experimental Design: Array-based comparative genomic hybridization was used to investigate the association of DNA copy number alterations with outcome in patients with colorectal liver metastasis resected with curative intent. DNA from 50 liver metastases was labeled and hybridized onto an array consisting of 2,463 bacterial artificial chromosome clones covering the entire genome. The total fraction of genome altered (FGA) in the metastases and the patient's clinical risk score (CRS) were calculated to identify independent prognostic factors for survival., Results: An average of 30 +/- 14% of the genome was altered in the liver metastases (14% gained and 16% lost). As expected, a lower CRS was an independent predictor of overall survival (P = 0.03). In addition, a high FGA also was an independent predictor of survival (P = 0.01). The median survival time in patients with a low CRS (score 0-2) and a high (> or =20%) FGA was 38 months compared with 18 months in patients with a low CRS and a low FGA. Supervised analyses, using Prediction Analysis of Microarrays and Significance Analysis of Microarrays, identified a set of clones, predominantly located on chromosomes 7 and 20, which best predicted survival., Conclusions: Both FGA and CRS are independent predictors of survival in patients with resected hepatic colorectal cancer metastases. The greater the FGA, the more likely the patient is to survive.
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- 2005
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225. Efficacy and safety of liposomal anthracyclines in phase I/II clinical trials.
- Author
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Alberts DS, Muggia FM, Carmichael J, Winer EP, Jahanzeb M, Venook AP, Skubitz KM, Rivera E, Sparano JA, DiBella NJ, Stewart SJ, Kavanagh JJ, and Gabizon AA
- Subjects
- Antibiotics, Antineoplastic adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Clinical Trials, Phase I as Topic, Clinical Trials, Phase II as Topic, Daunorubicin adverse effects, Doxorubicin adverse effects, Humans, Liposomes, Antibiotics, Antineoplastic administration & dosage, Daunorubicin administration & dosage, Doxorubicin administration & dosage
- Abstract
Preclinical studies have established the pharmacologic advantages of liposomal anthracyclines, including pharmacokinetic profiles after bolus dosing that resemble continuous infusion of conventional anthracyclines, increased drug concentrations in tumor cells compared with the surrounding tissues, and reduced toxicity relative to conventional anthracycline treatment. Based on these studies, many phase I and phase II clinical trials were conducted to assess the safety and potential activity of liposomal anthracyclines in the management of both solid and hematologic tumors. These studies provided valuable insight into the safety of pegylated liposomal doxorubicin (Doxil/Caelyx [PLD]), nonpegylated liposomal doxorubicin (Myocet [NPLD]), and liposomal daunorubicin (DaunoXome [DNX]) over a range of doses, either as single-agent therapy or in combination with other cytotoxic agents. Other liposomal anthracyclines in development may be well tolerated but their activity remains to be elucidated by clinical trials. The available data also suggest that liposomal anthracyclines have activity not only against tumor types with known sensitivity to conventional anthracyclines, but also potentially for tumors that are typically anthracycline-resistant. Despite the availability of clinical data from a wide variety of tumor types and patient populations, further studies of liposomal anthracycline therapy are needed to fully establish their safety, efficacy, and dosing in the treatment of these patients.
- Published
- 2004
- Full Text
- View/download PDF
226. Cetuximab in the treatment of colorectal cancer.
- Author
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Goldberg RM, Venook AP, and Schilsky RL
- Subjects
- Antibodies, Monoclonal adverse effects, Antibodies, Monoclonal, Humanized, Cetuximab, Chemotherapy, Adjuvant, Clinical Trials as Topic, Colorectal Neoplasms pathology, Humans, Neoplasm Metastasis, Antibodies, Monoclonal administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Colorectal Neoplasms drug therapy
- Published
- 2004
227. Key research issues in the management of hepatocellular carcinoma.
- Author
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Venook AP
- Subjects
- Clinical Trials as Topic, Humans, Neoplasm Staging, Research Design, Carcinoma, Hepatocellular therapy, Liver Neoplasms therapy
- Abstract
Hepatocellular carcinoma (HCC) is an extremely diverse and heterogeneous disease and improving patient outcome is a difficult undertaking. While many therapeutic options exist, few have been subjected to rigorous study, so patient benefit is uncertain. Comparative trials need to be performed to determine the value of these and, of course, newer treatments. However, there are numerous challenges to the design and conduct of such studies. While stratification parameters are important in most clinical trials, they are particularly critical when studying HCC. The cancer staging of HCC must reflect prognosis and, therefore, must include parameters of liver disease. This is because the underlying hepatic dysfunction may often determine how long patients survive and confuse the interpretation of anti-HCC treatment trials. Two new staging paradigms--Cancer of the Liver Italian Program (CLIP) and Chinese University Prognostic Index (CUPI)--have been developed, and these need to be validated. The role of the many different treatment options must be determined. However, the diverse nature of presentation of HCC and the proliferation of many routine procedures--such as chemoembolization or radiofrequency ablation--make controlled trials nearly impossible. Even drug development is a special circumstance, because HCC patients with underlying liver disease may need different dosing regimens and schedules compared to other cancer patients. This makes clinical trial design more cumbersome and the risks of participating in clinical trials for HCC greater. The immense unique challenges of this disease make it imperative for investigators to identify the most promising agents for HCC. At the same time, all patients with HCC should, if possible, be treated on well-designed clinical trials.
- Published
- 2004
- Full Text
- View/download PDF
228. Emerging therapies for metastatic colorectal cancer: focus on EGFR and VEGF inhibition.
- Author
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Venook AP
- Subjects
- Angiogenesis Inhibitors therapeutic use, Antibodies, Monoclonal therapeutic use, Antibodies, Monoclonal, Humanized, Antineoplastic Agents, Phytogenic therapeutic use, Bevacizumab, Camptothecin analogs & derivatives, Camptothecin therapeutic use, Cetuximab, Clinical Trials as Topic statistics & numerical data, Colorectal Neoplasms pathology, Drug Therapy, Combination, Humans, Irinotecan, Neoplasm Metastasis, Antineoplastic Agents therapeutic use, Colorectal Neoplasms drug therapy, ErbB Receptors antagonists & inhibitors, Vascular Endothelial Growth Factor A antagonists & inhibitors
- Abstract
Despite recent advances in chemotherapy, including the development of irinotecan and oxaliplatin, survival of patients with advanced colorectal cancer remains suboptimal. Thanks to an increased understanding of the biologic basis of cancer, investigators are turning to molecularly targeted therapy to further improve outcome. Current research in colorectal cancer focuses on inhibiting the epidermal growth factor receptor and vascular endothelial growth factor. Both are essential to tumor growth and frequently over-expressed in colorectal cancer cells. Epidermal growth factor receptor pathways promote survival of tumor cells through cell proliferation, differentiation, migration, adhesion, and transformation and inhibition of apoptosis, whereas the vascular endothelial growth factor is a key mediator of angiogenesis and may have other biologic roles. Recent phase II and III results show the feasibility and activity of inhibiting both by using monoclonal antibodies in combination with chemotherapy in patients with advanced colorectal cancer. Cetuximab (an epidermal growth factor receptor antibody) plus irinotecan yields an increased overall response in patients with irinotecan-refractory colorectal disease. In previously untreated patients, irinotecan/5-fluoruoracil/leucovorin plus cetuximab also generates an increased overall response rate. Randomized trials of the humanized anti-vascular endothelial growth factor antibody (rhuMAb vascular endothelial growth factor) plus chemotherapy yielded increased overall response rates and median survival times compared with chemotherapy alone. The primary toxicity of cetuximab is an acneform skin rash; rhuMAb vascular endothelial growth factor causes mild hypertension and may cause perturbations in coagulation. Treatment with either does not appear to exacerbate chemotherapy-related toxicity.
- Published
- 2004
229. Hepatocellular carcinoma: regional therapy with a magnetic targeted carrier bound to doxorubicin in a dual MR imaging/ conventional angiography suite--initial experience with four patients.
- Author
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Wilson MW, Kerlan RK Jr, Fidelman NA, Venook AP, LaBerge JM, Koda J, and Gordon RL
- Subjects
- Adult, Aged, Carcinoma, Hepatocellular diagnostic imaging, Carcinoma, Hepatocellular pathology, Drug Carriers, Equipment Design, Female, Humans, Liver Neoplasms diagnostic imaging, Liver Neoplasms pathology, Magnetics instrumentation, Male, Middle Aged, Angiography, Antibiotics, Antineoplastic administration & dosage, Carcinoma, Hepatocellular drug therapy, Doxorubicin administration & dosage, Liver Neoplasms drug therapy, Magnetic Resonance Imaging instrumentation
- Abstract
Four patients with inoperable hepatocellular carcinoma were treated with a magnetic targeted carrier bound to doxorubicin (MTC-DOX) by using a joint magnetic resonance (MR) imaging/conventional angiography system consisting of a 1.5-T short-bore magnet connected to a C-arm angiography unit by a sliding tabletop. Selective transcatheter delivery of the MTC-DOX to the hepatic artery was monitored by using intraprocedural MR imaging, and interim catheter manipulation was performed with fluoroscopic guidance to optimize agent delivery to the tumor and minimize delivery to normal tissue. The final fraction of treated tumor volume ranged from 0.64 to 0.91. The fraction of affected normal liver volume ranged from 0.07 to 0.30. The dual MR imaging/conventional angiography system shows promise for directing magnetically targeted tumor therapies., (Copyright RSNA, 2004)
- Published
- 2004
- Full Text
- View/download PDF
230. A phase I and pharmacokinetic study of irinotecan in patients with hepatic or renal dysfunction or with prior pelvic radiation: CALGB 9863.
- Author
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Venook AP, Enders Klein C, Fleming G, Hollis D, Leichman CG, Hohl R, Byrd J, Budman D, Villalona M, Marshall J, Rosner GL, Ramirez J, Kastrissios H, and Ratain MJ
- Subjects
- Adult, Aged, Antineoplastic Agents, Phytogenic administration & dosage, Camptothecin administration & dosage, Female, Humans, Irinotecan, Male, Middle Aged, Pelvis radiation effects, Radiotherapy, Antineoplastic Agents, Phytogenic adverse effects, Antineoplastic Agents, Phytogenic pharmacokinetics, Camptothecin adverse effects, Camptothecin analogs & derivatives, Camptothecin pharmacokinetics, Kidney Diseases complications, Liver Diseases complications, Neoplasms drug therapy
- Abstract
Background: To ascertain if hepatic or renal dysfunction or prior pelvic radiation (XRT) leads to increased toxicity at a given dose of irinotecan and to characterize the pharmacokinetics of irinotecan and its major metabolites in patients with hepatic or renal dysfunction., Patients and Methods: Adults with tumors appropriate for irinotecan therapy and who had abnormal liver or renal function tests or had prior radiation to the pelvis were eligible. Patients were assigned to one of four treatment cohorts: I, aspartate aminotransferase (AST) > or = 3x upper limit of normal and direct bilirubin <1.0 mg/dl; II, direct bilirubin 1.0-7.0 mg/dl; III, creatinine 1.6-5.0 mg/dl with normal liver function; IV, prior pelvic XRT with normal liver and renal function. Starting with reduced doses of either 145 or 225 mg/m(2), irinotecan was administered every 3 weeks to at least three patients within each cohort. Irinotecan and its metabolites in the blood were measured in all patients., Results: Thirty-five patients were evaluable for toxicity. No dose-limiting toxicity was seen in cohort I, although only three patients were treated and at a dose of 225 mg/m(2). Patients with elevations of direct bilirubin had dose-limiting toxicities, even though the starting dose was 145 mg/m(2). These same patients appeared to have comparable exposure to the active metabolite SN-38 as normal patients treated with full-dose irinotecan. Patients with elevations of creatinine or with prior pelvic radiotherapy did not appear to have increased risk of toxicity at the doses explored in this study., Conclusions: Patients with elevated bilirubin treated with irinotecan have an increased risk of toxicity and a dose reduction is recommended. Patients with elevated AST, creatinine or prior pelvic radiation do not appear to have increased sensitivity to irinotecan, but the data are not adequate to support a specific dosing recommendation.
- Published
- 2003
- Full Text
- View/download PDF
231. Induction therapy in patients with metastatic colorectal cancer.
- Author
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Venook AP
- Subjects
- Antineoplastic Agents therapeutic use, Camptothecin administration & dosage, Camptothecin therapeutic use, Colorectal Neoplasms pathology, Fluorouracil administration & dosage, Fluorouracil therapeutic use, Hepatic Artery, Humans, Infusions, Intra-Arterial, Irinotecan, Neoadjuvant Therapy, Organoplatinum Compounds administration & dosage, Organoplatinum Compounds therapeutic use, Oxaliplatin, Antineoplastic Agents administration & dosage, Camptothecin analogs & derivatives, Colorectal Neoplasms drug therapy, Liver Neoplasms drug therapy, Liver Neoplasms secondary
- Published
- 2003
- Full Text
- View/download PDF
232. Colorectal metastases confined to the liver: a unique opportunity?
- Author
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Venook AP
- Subjects
- Antineoplastic Agents pharmacology, Chemotherapy, Adjuvant, Combined Modality Therapy, Humans, Infusions, Intra-Arterial, Infusions, Intravenous, Liver Neoplasms drug therapy, Liver Neoplasms surgery, Neoadjuvant Therapy, Patient Care Planning, Patient Selection, Prognosis, Antineoplastic Agents administration & dosage, Colorectal Neoplasms pathology, Liver Neoplasms secondary
- Abstract
Liver metastases nearly always represent disseminated cancer, and systemic therapies designed for controlling systemic tumors are usually indicated. However, in a minority of patients with colorectal cancer, management of the metastatic hepatic disease will be clinically important and even curative. This review discusses novel treatment approaches that may be indicated in colorectal cancer patients with liver metastases, including the potential use of systemic therapy as part of multimodality therapy in an effort to cure selected patients with colorectal liver metastases.
- Published
- 2003
- Full Text
- View/download PDF
233. Adjuvant and neoadjuvant therapy for esophageal cancer: a critical reappraisal.
- Author
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Visser BC, Venook AP, and Patti MG
- Subjects
- Adenocarcinoma mortality, Clinical Trials as Topic, Esophageal Neoplasms mortality, Humans, Prognosis, Survival Rate, Adenocarcinoma therapy, Esophageal Neoplasms therapy, Neoadjuvant Therapy methods
- Abstract
Despite important refinements of surgical technique and significant progress in perioperative care, esophageal cancer remains highly lethal. Therefore, hope for improvement in the prognosis of esophageal cancer lies largely in the use of additional therapy. Promising data from numerous Phase II trials and a single Phase III trial led to the widespread adoption of neoadjuvant chemoradiotherapy. However, subsequent randomized trials did not conclusively demonstrate a survival benefit with any of the current neoadjuvant protocols for patients with resectable esophageal cancer. Benefit, if any, exists only for complete pathologic responders. Neoadjuvant chemoradiation should not be used in patients with resectable esophageal cancer outside of the clinical trials. Future investigation must focus on the development of new biologic or chemotherapeutic agents, and the identification of biologic markers that might predict response to chemoradiation.
- Published
- 2003
- Full Text
- View/download PDF
234. Testing the water before diving off the cutting edge.
- Author
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Venook AP
- Subjects
- Antineoplastic Combined Chemotherapy Protocols, Catheter Ablation, Evidence-Based Medicine, Humans, Infusions, Intra-Arterial, Liver Neoplasms secondary, Treatment Outcome, Liver Neoplasms drug therapy, Liver Neoplasms mortality
- Published
- 2003
- Full Text
- View/download PDF
235. Shedding old paradigms: developing viruses to treat cancer.
- Author
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Bergsland EK and Venook AP
- Subjects
- Adenoviridae genetics, Clinical Trials, Phase I as Topic, Humans, Neoplasms genetics, Paramyxoviridae genetics, Genetic Therapy methods, Neoplasms therapy, Viruses genetics
- Published
- 2002
- Full Text
- View/download PDF
236. Therapeutic approaches to metastasis confined to the liver.
- Author
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Venook AP and Warren RS
- Subjects
- Antimetabolites, Antineoplastic administration & dosage, Antimetabolites, Antineoplastic therapeutic use, Chemotherapy, Adjuvant, Floxuridine administration & dosage, Floxuridine therapeutic use, Fluorouracil administration & dosage, Fluorouracil therapeutic use, Hepatic Artery, Humans, Infusions, Intra-Arterial, Liver Neoplasms drug therapy, Liver Neoplasms surgery, Chemoembolization, Therapeutic, Colorectal Neoplasms pathology, Liver Neoplasms secondary
- Abstract
Liver metastases nearly always represent disseminated cancer, and systemic therapies are usually indicated. However, in a minority of patients--some with colorectal cancer, others with selected tumors--management of the hepatic disease may be clinically important and even curative. This review identifies unique patient subgroups and novel treatment approaches that may be indicated in patients with liver metastases.
- Published
- 2001
- Full Text
- View/download PDF
237. Hepatocellular carcinoma.
- Author
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Venook AP
- Subjects
- Clinical Trials as Topic, Combined Modality Therapy, Hepatectomy, Humans, Liver Transplantation, Prognosis, Reoperation, Survival Rate, Carcinoma, Hepatocellular therapy, Liver Neoplasms therapy
- Abstract
Early detection of hepatocellular carcinoma (HCC) is feasible, particularly in patients known to be at risk from chronic hepatitis and chronic liver disease. The optimal surveillance strategy is unknown. HCC usually presents as an incurable disease even when detected on surveillance. Surgical resection is the treatment of choice, but the coexistence of chronic liver disease and the insidious nature of HCC make it unresectable in most patients. Orthotopic liver transplantation for selected patients or ablative techniques may offer an opportunity to render patients disease-free even if the tumor is unresectable. There are numerous therapies offered to patients with unresectable HCC, including chemotherapy, hormonal therapy, and regional intra-arterial treatments. While potentially palliative, none of these approaches has been demonstrated to prolong survival in these patients. If possible, the treatment of patients with HCC should be done on clinical trials.
- Published
- 2000
- Full Text
- View/download PDF
238. Phase I and pharmacokinetic trial of gemcitabine in patients with hepatic or renal dysfunction: Cancer and Leukemia Group B 9565.
- Author
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Venook AP, Egorin MJ, Rosner GL, Hollis D, Mani S, Hawkins M, Byrd J, Hohl R, Budman D, Meropol NJ, and Ratain MJ
- Subjects
- Aged, Antimetabolites, Antineoplastic blood, Antimetabolites, Antineoplastic pharmacokinetics, Aspartate Aminotransferases blood, Bilirubin blood, Creatinine blood, Deoxycytidine blood, Deoxycytidine pharmacokinetics, Deoxycytidine therapeutic use, Female, Humans, Liver Diseases blood, Liver Function Tests, Male, Middle Aged, Models, Biological, Neoplasms blood, Renal Insufficiency blood, Gemcitabine, Antimetabolites, Antineoplastic therapeutic use, Deoxycytidine analogs & derivatives, Liver Diseases complications, Neoplasms complications, Neoplasms drug therapy, Renal Insufficiency complications
- Abstract
Purpose: To ascertain if hepatic or renal dysfunction leads to increased toxicity at a given dose of gemcitabine and to characterize the pharmacokinetics of gemcitabine and its major metabolite in patients with such dysfunction., Patients and Methods: Adults with tumors appropriate for gemcitabine therapy and who had abnormal liver or renal function tests were eligible. Patients were assigned to one of three treatment cohorts: I-AST level less than or equal to two times normal and bilirubin level less than 1.6 mg/dL; II-bilirubin level 1.6 to 7.0 mg/dL; and III-creatinine level 1.6 to 5.0 mg/dL with normal liver function. Doses were explored in at least three patients within each cohort. Gemcitabine and its metabolite were to be measured in the blood in all patients., Results: Forty patients were assessable for toxicity. Transient transaminase elevations were observed in many patients but were not dose limiting. Patients with AST elevations tolerated gemcitabine without increased toxicity, but patients with elevated bilirubin levels had significant deterioration in liver function after gemcitabine therapy. Patients with elevated creatinine levels had significant toxicity even at reduced doses of gemcitabine, including two instances of severe skin toxicity. There were no apparent pharmacokinetic differences among the three groups or compared with historical controls., Conclusion: If gemcitabine is used for patients with elevations in AST level, no dose reduction is necessary. Patients with elevated bilirubin levels have an increased risk of hepatic toxicity, and a dose reduction is recommended. Patients with elevated creatinine levels seem to have increased sensitivity to gemcitabine, but the data are not adequate to support a specific dosing recommendation.
- Published
- 2000
- Full Text
- View/download PDF
239. Hepatocellular carcinoma.
- Author
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Bergsland EK and Venook AP
- Subjects
- Animals, Combined Modality Therapy, Disease Models, Animal, Drug Therapy, Hormone Replacement Therapy, Humans, Immunotherapy, Neoplasm Recurrence, Local, Carcinoma, Hepatocellular epidemiology, Carcinoma, Hepatocellular pathology, Carcinoma, Hepatocellular therapy, Liver Neoplasms epidemiology, Liver Neoplasms pathology, Liver Neoplasms therapy
- Abstract
Hepatocellular carcinoma (HCC) is a disease that is extremely difficult to manage and is increasing markedly in incidence. This presents both an opportunity and a challenge. At-risk patients can be identified and early detection of HCC is feasible. New surgical techniques and postoperative therapies, including hepatic intra-arterial radiation, may improve the outlook for some patients with resectable cancer. Unfortunately, the vast majority of patients with HCC will have unresectable cancers. Regional treatments may shrink or necrose tumors, but no clear benefit to such therapies has been demonstrated. Recent evidence suggests combination chemotherapy may help some patients, although this needs validation. Perhaps the best hope is that the further elucidation of the genetic and molecular features of HCC will lend us insight into innovative strategies to manage this difficult cancer.
- Published
- 2000
- Full Text
- View/download PDF
240. Hepatic arterial infusion of chemotherapy for metastatic colorectal cancer.
- Author
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Venook AP, Althaus B, and Warren RS
- Subjects
- Colorectal Neoplasms pathology, Dexamethasone administration & dosage, Humans, Infusion Pumps, Implantable, Infusions, Intra-Arterial, Adenocarcinoma drug therapy, Adenocarcinoma secondary, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Floxuridine administration & dosage, Liver Neoplasms drug therapy, Liver Neoplasms secondary
- Published
- 2000
- Full Text
- View/download PDF
241. Regional strategies for managing hepatocellular carcinoma.
- Author
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Venook AP
- Subjects
- Antineoplastic Combined Chemotherapy Protocols administration & dosage, Chemoembolization, Therapeutic, Contrast Media therapeutic use, Humans, Infusions, Intra-Arterial, Iodized Oil therapeutic use, Radiotherapy methods, Carcinoma, Hepatocellular therapy, Liver Neoplasms therapy
- Abstract
Hepatocellular carcinoma is a common, difficult-to-treat cancer that has a variable natural history depending on patient demographics and the etiology and extent of underlying liver disease. Resection is the preferred treatment option but is only possible in the rare patient who has adequate hepatic reserve and limited-stage cancer. Systemic chemotherapy is mostly inactive. Because most patients with hepatocellular cancer succumb to hepatic failure, this is a disease that appears to be amenable to regional treatments. For this reason, numerous intratumoral, ablative techniques are available. Other routinely used regional treatment modalities include intraarterial chemotherapy, chemoembolization, Lipiodol chemoembolization, and internal radiation. However, the benefits of these interventions have been difficult to ascertain given the variable clinical course of the disease. Regional delivery may prove to be most valuable as a route for administering newer agents.
- Published
- 2000
242. Transcatheter embolization for the treatment of misperfusion after hepatic artery chemoinfusion pump implantation.
- Author
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Bloom AI, Gordon RL, Ahl KH, Kerlan RK Jr, LaBerge JM, Wilson MW, Venook AP, and Warren R
- Subjects
- Adult, Aged, Aged, 80 and over, Colorectal Neoplasms pathology, Female, Follow-Up Studies, Humans, Male, Middle Aged, Retrospective Studies, Technetium Tc 99m Aggregated Albumin, Technetium Tc 99m Sulfur Colloid, Treatment Outcome, Embolization, Therapeutic methods, Hepatic Artery, Infusion Pumps, Implantable, Infusions, Intra-Arterial adverse effects, Liver Neoplasms drug therapy, Liver Neoplasms secondary
- Abstract
Background: The use of surgically implanted chemoinfusion pumps for the treatment of hepatic metastases from colorectal carcinoma can be complicated by intra- or extrahepatic misperfusion. This may result in suboptimal tumor exposure to the chemotherapeutic agent and injury to other gastrointestinal organs. Misperfusion can be managed by selective arterial transcatheter embolization., Methods: Between 1989 and 1996, 16 patients with liver metastases from colorectal carcinoma and with hepatic artery chemoinfusion pump misperfusion were treated using transcatheter coil embolization. Six female and 10 male patients (age range, 34-84 years; median, 51.5 years) were identified by retrospective review of the records of the Department of Interventional Radiology. After pump placement, abnormal liver perfusion scan or methylene blue endoscopy study results prompted angiography with coil embolization. After embolization, the imaging studies were repeated and patients were monitored in the Oncology Clinic., Results: Eight patients exhibited intrahepatic misperfusion (group 1) and eight extrahepatic misperfusion (group 2). Coil embolization was immediately successful in 100% of patients in group 1, with restoration of normal hepatic perfusion, and in 75% in group 2. There were no immediate procedure-related complications. Follow-up periods ranged from 1 to 23 months (median, 13.5 months). Embolization was unsuccessful for two patients (in group 2), who tolerated a modified chemotherapeutic regimen, with follow-up periods of 18.5 and 22 months., Conclusions: Transcatheter coil embolization is the therapy of choice for the management of hepatic artery chemoinfusion pump misperfusion. It is rapid, effective, and well tolerated by patients and obviates the need for additional surgical intervention.
- Published
- 1999
- Full Text
- View/download PDF
243. Octreotide acetate long-acting formulation versus open-label subcutaneous octreotide acetate in malignant carcinoid syndrome.
- Author
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Rubin J, Ajani J, Schirmer W, Venook AP, Bukowski R, Pommier R, Saltz L, Dandona P, and Anthony L
- Subjects
- Carcinoid Tumor blood, Carcinoid Tumor complications, Carcinoid Tumor urine, Delayed-Action Preparations, Diarrhea drug therapy, Dose-Response Relationship, Drug, Double-Blind Method, Drug Administration Schedule, Female, Gastrointestinal Agents blood, Humans, Hydroxyindoleacetic Acid urine, Injections, Intramuscular, Injections, Subcutaneous, Male, Malignant Carcinoid Syndrome blood, Malignant Carcinoid Syndrome urine, Middle Aged, Octreotide blood, Prospective Studies, Gastrointestinal Agents administration & dosage, Malignant Carcinoid Syndrome drug therapy, Octreotide administration & dosage
- Abstract
Purpose: Subcutaneous (SC) octreotide acetate effectively relieves the diarrhea and flushing associated with carcinoid syndrome but requires long-term multiple injections daily. A microencapsulated long-acting formulation (LAR) of octreotide acetate has been developed for once-monthly intramuscular dosing., Patients and Methods: A randomized trial compared double-blinded octreotide LAR at 10, 20, and 30 mg every 4 weeks with open-label SC octreotide every 8 hours for the treatment of carcinoid syndrome. Seventy-nine patients controlled with treatment of SC octreotide 0.3 to 0.9 mg/d whose symptoms returned during a washout period and who returned for at least the week 20 evaluation constituted the efficacy-assessable population., Results: Complete or partial treatment success was comparable in each of the four arms of the study (SC, 58.3%; 10 mg, 66.7%; 20 mg, 71.4%; 30 mg, 61.9%; P> or =.72 for all pairwise comparisons). Control of stool frequency was similar in all treatment groups. Flushing episodes were best controlled in the 20-mg LAR and SC groups; the 10-mg LAR treatment was least effective in the control of flushing. Treatment was well tolerated by patients in all four groups., Conclusion: Once octreotide steady-state concentrations are achieved, octreotide LAR controls the symptoms of carcinoid syndrome at least as well as SC octreotide. A starting dose of 20 mg of octreotide LAR is recommended. Supplemental SC octreotide is needed for approximately 2 weeks after initiation of octreotide LAR treatment. Occasional rescue SC injections may be required for possibly 2 to 3 months until steady-state octreotide levels from the LAR formulation are achieved.
- Published
- 1999
- Full Text
- View/download PDF
244. Embolization and chemoembolization therapy for neuroendocrine tumors.
- Author
-
Venook AP
- Subjects
- Adenoma, Islet Cell therapy, Carcinoid Tumor therapy, Humans, Malignant Carcinoid Syndrome therapy, Palliative Care, Chemoembolization, Therapeutic, Embolization, Therapeutic, Neuroendocrine Tumors therapy
- Abstract
Neuroendocrine tumors, particularly those of gastrointestinal tract origin, have a predisposition for metastasizing to the liver. In such patients, the clinical course is often dominated by the hepatic disease, either because of hormone secretion or because of tumor bulk. Because the liver has a dual vascular supply and hepatic metastases derive the majority of blood from the hepatic artery, the regional delivery of chemotherapy can offer pharmacokinetic advantages over systemic administration. The hepatic artery is also a nonsurgical avenue for inducing selective metastasis ischemia by the embolization of tumor vessels. The combination of these two therapies, or chemoembolization, may provide additive benefits. Such an approach has been demonstrated to reduce tumor bulk, reduce hormone levels, and palliate the symptoms of many patients with liver-dominant neuroendocrine metastases. Embolization or chemoembolization is an appropriate modality for some patients with neuroendocrine tumors.
- Published
- 1999
- Full Text
- View/download PDF
245. Tamoxifen in liver disease: potential exacerbation of hepatic dysfunction.
- Author
-
Floren LC, Hebert MF, Venook AP, Jordan VC, Cisneros A, and Somberg KA
- Subjects
- Antineoplastic Agents, Hormonal adverse effects, Antineoplastic Agents, Hormonal pharmacokinetics, Breast Neoplasms complications, Breast Neoplasms metabolism, Chemical and Drug Induced Liver Injury blood, Female, Humans, Liver Diseases blood, Liver Function Tests, Middle Aged, Tamoxifen adverse effects, Tamoxifen pharmacokinetics, Antineoplastic Agents, Hormonal therapeutic use, Breast Neoplasms drug therapy, Chemical and Drug Induced Liver Injury etiology, Liver Diseases complications, Tamoxifen therapeutic use
- Abstract
Tamoxifen, a non-steroidal anti-estrogen, has been used successfully for a decade as post-operative adjuvant therapy for breast cancer. Tamoxifen is generally well tolerated with few side effects, especially at the typical dose of 10 mg twice daily. However, hepatic effects have been reported after tamoxifen administration and are usually found to be cholestatic in nature. Although previous reports concentrate on tamoxifen as a probable cause of drug-induced hepatotoxicity, very little attention has been focused on the use of tamoxifen in patients with pre-existing liver dysfunction and the possible need for dose adjustment. We present the case of a 48-year-old woman with an acute exacerbation of her pre-existing liver dysfunction and subsequent elevations of tamoxifen blood levels after approximately one year of tamoxifen therapy for adjuvant treatment of breast cancer. Tamoxifen dosing was adjusted based on serum levels.
- Published
- 1998
- Full Text
- View/download PDF
246. Phase I and pharmacokinetic trial of paclitaxel in patients with hepatic dysfunction: Cancer and Leukemia Group B 9264.
- Author
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Venook AP, Egorin MJ, Rosner GL, Brown TD, Jahan TM, Batist G, Hohl R, Budman D, Ratain MJ, Kearns CM, and Schilsky RL
- Subjects
- Adult, Aged, Antineoplastic Agents, Phytogenic administration & dosage, Antineoplastic Agents, Phytogenic adverse effects, Bilirubin blood, Chromatography, High Pressure Liquid, Cohort Studies, Female, Humans, Infusions, Intravenous, Male, Middle Aged, Neoplasms drug therapy, Neoplasms metabolism, Neoplasms physiopathology, Paclitaxel administration & dosage, Paclitaxel adverse effects, Antineoplastic Agents, Phytogenic pharmacokinetics, Liver physiopathology, Paclitaxel pharmacokinetics
- Abstract
Purpose: To characterize the maximum-tolerated dose, dose-limiting toxicities (DLTs), and pharmacokinetics of paclitaxel in patients with abnormal liver function., Patients and Methods: Adults with tumors appropriate for paclitaxel therapy who had abnormal liver function tests were eligible. Patients were assigned to one of three treatment cohorts: I, AST level twofold normal and bilirubin level less than 1.5 mg/dL; II, bilirubin level 1.6 to 3.0 mg/dL; and III, bilirubin level greater than 3.0 mg/dL. Doses were explored in at least three patients within each cohort. Although designed to assess a 24-hour infusion schedule, the trial was extended to also assess a 3-hour regimen. Pharmacokinetics were to be studied in all patients., Results: Eighty-one patients were assessable for toxicity. Patients with bilirubin levels greater than 1.5 mg/dL had substantial toxicity at all doses explored, whereas the toxicity for patients with elevated AST levels occurred at doses that ranged from 50 to 175 mg/m2 administered over 24 hours. In most patients, the DLT was myelosuppression. The pharmacokinetic data were insufficient to adequately evaluate the relationship between pharmacokinetics and toxicity in patients who received 24-hour infusions but provided evidence of a longer exposure to paclitaxel than anticipated for the doses used in this study in the 3-hour infusion group., Conclusion: If paclitaxel is used for patients with elevated levels of AST or bilirubin, dose reductions are necessary, and an increase in toxicity can be anticipated. The increased myelosuppression observed is at least partially because of altered paclitaxel pharmacokinetics in such patients.
- Published
- 1998
- Full Text
- View/download PDF
247. Update on hepatic intra-arterial chemotherapy.
- Author
-
Venook AP
- Subjects
- Humans, Infusions, Intra-Arterial, Randomized Controlled Trials as Topic, Antineoplastic Agents administration & dosage, Colorectal Neoplasms pathology, Hepatic Artery, Liver Neoplasms drug therapy, Liver Neoplasms secondary
- Abstract
The use of hepatic intra-arterial (HIA) chemotherapy is based on the pharmacologic principle that the regional administration of certain drugs can lead to higher drug concentrations at the site of a tumor. This has been studied most extensively in patients with liver-only colorectal metastases. Four large randomized studies have failed to demonstrate a survival advantage of regional treatment over systemic chemotherapy, although two meta-analyses confirmed an improvement in response rate and suggest a trend toward improvement in survival. Two randomized studies have shown improved survival in patients treated with HIA chemotherapy, as compared with those given supportive care, and quality of life also appears to be superior in HIA chemotherapy recipients. The treatment employed in all of the randomized studies was hindered by substantial hepatobiliary toxicity and many surgical complications. Improved surgical techniques and newer chemotherapy combinations appear to have improved phase II results with HIA therapy, leading to a randomized trial now being conducted by the Cancer and Leukemia Group B (CALGB). The role of HIA chemotherapy in adjuvant settings and in other diseases has not been as well-studied, and such uses remain appropriate only for very selected patients. Ultimately, the regional advantage gained by the HIA route may prove to be most advantageous for the delivery of newer biologic agents.
- Published
- 1997
248. Can a vitamin prevent hepatocellular carcinoma?
- Author
-
Venook AP
- Subjects
- Humans, Tretinoin therapeutic use, Anticarcinogenic Agents therapeutic use, Carcinoma, Hepatocellular prevention & control, Liver Neoplasms prevention & control, Tretinoin analogs & derivatives
- Published
- 1997
- Full Text
- View/download PDF
249. Intra-abdominal desmoplastic small round-cell tumor: expansion of the pathologic profile.
- Author
-
Dorsey BV, Benjamin LE, Rauscher F 3rd, Klencke B, Venook AP, Warren RS, and Weidner N
- Subjects
- Adult, Base Sequence, Biomarkers, Tumor analysis, Humans, Immunohistochemistry, Male, Microscopy, Electron, Polymerase Chain Reaction, Carcinoma, Small Cell pathology, Omentum pathology, Peritoneal Neoplasms pathology
- Abstract
This report describes an intra-abdominal desmoplastic small round-cell tumor in a 29-year-old man that significantly differed from the classically described appearances of this unique tumor. It showed extensive papillary areas, no necrosis, and very little desmoplasia. The latter was limited, paucicellular, and present in areas separate from the papillary structures. Also, areas of back-to-back, single-cell infiltration, which mimicked lobular breast carcinoma, were present. These epithelial features suggested the diagnosis of adenocarcinoma or peculiar mesothelioma. But, the immunohistochemical features (tumor cells positive for keratin, desmin, and vimentin) were more consistent with an intra-abdominal desmoplastic small round-cell tumor. The diagnosis became clear after application of reverse transcriptase-polymerase chain reaction techniques to formalin-fixed, paraffin-embedded tissue, which showed the presence of a 100-base pair product containing the fusion junction of Ewing's sarcoma-1 exon 7 to Wilms' tumor-1 exon 8. This feature is considered unique to intra-abdominal desmoplastic small round-cell tumors. This case illustrates the less common histologic findings that can be found in intra-abdominal desmoplastic small round-cell tumor. This deviation from the classic histologic findings may be an expression of an uncommon morphologic variant and/or partially produced by the effects of prior chemotherapy. In either event, only by illustrating the various histologic appearances of intra-abdominal desmoplastic small round-cell tumor are the chances increased for the accurate diagnosis of this aggressive neoplasm with a poor prognosis.
- Published
- 1996
250. Regional chemotherapy approaches for primary and metastatic liver tumors.
- Author
-
Venook AP and Warren RS
- Subjects
- Antineoplastic Agents administration & dosage, Biological Products administration & dosage, Biological Products therapeutic use, Carcinoma, Hepatocellular drug therapy, Chemoembolization, Therapeutic, Clinical Protocols, Colonic Neoplasms pathology, Genetic Therapy, Humans, Liver Neoplasms secondary, Liver Neoplasms surgery, Liver Neoplasms therapy, Rectal Neoplasms pathology, Remission Induction, Survival Rate, Antineoplastic Agents therapeutic use, Chemotherapy, Cancer, Regional Perfusion, Liver Neoplasms drug therapy
- Abstract
There are pharmacologic principles that make regional chemotherapy to the liver a logical treatment strategy. Patients with colorectal liver metastases and hepatocellular carcinoma would appear to be the best candidates for such an approach. Although there are many objective responses to such treatment, survival benefit has not been demonstrated, but new regimens and refined techniques appear to be improving results. Ultimately, regional delivery may be best suited for innovative treatments such as biologicals and gene therapies.
- Published
- 1996
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