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1.
J Clin Oncol ; 41(30): 4714-4720, 2023 Oct 20.
Article in English | MEDLINE | ID: mdl-37847995

ABSTRACT

PURPOSE: Patients with advanced pancreatic cancer have a poor prognosis and there have been no improvements in survival since the introduction of gemcitabine in 1996. Pancreatic tumors often overexpress human epidermal growth factor receptor type 1 (HER1/EGFR) and this is associated with a worse prognosis. We studied the effects of adding the HER1/EGFR-targeted agent erlotinib to gemcitabine in patients with unresectable, locally advanced, or metastatic pancreatic cancer. PATIENTS AND METHODS: Patients were randomly assigned 1:1 to receive standard gemcitabine plus erlotinib (100 or 150 mg/d orally) or gemcitabine plus placebo in a double-blind, international phase III trial. The primary end point was overall survival. RESULTS: A total of 569 patients were randomly assigned. Overall survival based on an intent-to-treat analysis was significantly prolonged on the erlotinib/gemcitabine arm with a hazard ratio (HR) of 0.82 (95% CI, 0.69 to 0.99; P = .038, adjusted for stratification factors; median 6.24 months v 5.91 months). One-year survival was also greater with erlotinib plus gemcitabine (23% v 17%; P = .023). Progression-free survival was significantly longer with erlotinib plus gemcitabine with an estimated HR of 0.77 (95% CI, 0.64 to 0.92; P = .004). Objective response rates were not significantly different between the arms, although more patients on erlotinib had disease stabilization. There was a higher incidence of some adverse events with erlotinib plus gemcitabine, but most were grade 1 or 2. CONCLUSION: To our knowledge, this randomized phase III trial is the first to demonstrate statistically significantly improved survival in advanced pancreatic cancer by adding any agent to gemcitabine. The recommended dose of erlotinib with gemcitabine for this indication is 100 mg/d.

2.
AACE Clin Case Rep ; 6(5): e239-e242, 2020.
Article in English | MEDLINE | ID: mdl-32984529

ABSTRACT

OBJECTIVE: Immune checkpoint inhibitors are approved to treat multiple cancers. We report life-threatening hepatic failure in 2 consecutive patients with Cushing syndrome that were treated with ketoconazole (KTZ) in combination with 2 different programmed cell death protein 1 (PD-1) inhibitors, Nivolumab and Pembrolizumab. METHODS: The first patient suffered from corticotroph pituitary carcinoma and the second from metastatic adrenal cortical carcinoma. They were both treated with KTZ for tumor-associated hypercortisolism. RESULTS: Hepatic function was normal on KTZ prior to initiation of PD-1 inhibitors, after which they rapidly developed severe hepatic dysfunction. In both cases, liver biopsy was consistent with drug-induced hepatic injury. Liver function fully recovered on discontinuing KTZ and the PD-1 inhibitors along with methylprednisone therapy. CONCLUSION: Antifungal azole therapy is commonly used in oncology patients who may be co-treated with PD-1 inhibitors. Although the specific combination of KTZ and PD-1 inhibitors to treat Cushing syndrome may be relatively uncommon, we recommend careful monitoring of hepatic function using a combination PD-1 inhibitors and azole antifungal agents, especially KTZ, due to the potential of life-threatening hepatic failure.

3.
J Clin Oncol ; 25(15): 1960-6, 2007 May 20.
Article in English | MEDLINE | ID: mdl-17452677

ABSTRACT

PURPOSE: Patients with advanced pancreatic cancer have a poor prognosis and there have been no improvements in survival since the introduction of gemcitabine in 1996. Pancreatic tumors often overexpress human epidermal growth factor receptor type 1 (HER1/EGFR) and this is associated with a worse prognosis. We studied the effects of adding the HER1/EGFR-targeted agent erlotinib to gemcitabine in patients with unresectable, locally advanced, or metastatic pancreatic cancer. PATIENTS AND METHODS: Patients were randomly assigned 1:1 to receive standard gemcitabine plus erlotinib (100 or 150 mg/d orally) or gemcitabine plus placebo in a double-blind, international phase III trial. The primary end point was overall survival. RESULTS: A total of 569 patients were randomly assigned. Overall survival based on an intent-to-treat analysis was significantly prolonged on the erlotinib/gemcitabine arm with a hazard ratio (HR) of 0.82 (95% CI, 0.69 to 0.99; P = .038, adjusted for stratification factors; median 6.24 months v 5.91 months). One-year survival was also greater with erlotinib plus gemcitabine (23% v 17%; P = .023). Progression-free survival was significantly longer with erlotinib plus gemcitabine with an estimated HR of 0.77 (95% CI, 0.64 to 0.92; P = .004). Objective response rates were not significantly different between the arms, although more patients on erlotinib had disease stabilization. There was a higher incidence of some adverse events with erlotinib plus gemcitabine, but most were grade 1 or 2. CONCLUSION: To our knowledge, this randomized phase III trial is the first to demonstrate statistically significantly improved survival in advanced pancreatic cancer by adding any agent to gemcitabine. The recommended dose of erlotinib with gemcitabine for this indication is 100 mg/d.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Pancreatic Neoplasms/drug therapy , Adenocarcinoma/secondary , Adult , Aged , Aged, 80 and over , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Double-Blind Method , Erlotinib Hydrochloride , Female , Humans , International Agencies , Male , Middle Aged , Pancreatic Neoplasms/pathology , Placebos , Prognosis , Quinazolines/administration & dosage , Survival Rate , Treatment Outcome , Gemcitabine
4.
J Nucl Med ; 46(4): 587-95, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15809480

ABSTRACT

UNLABELLED: The aim of this study was to compare PET with (18)F-FDG PET, in-line PET/CT, and software fusion of independently acquired CT and PET scans for staging of recurrent colorectal cancer (CRC). METHODS: Fifty-one patients with suspected recurrent CRC were studied with in-line PET/CT. Thirty-four of these patients underwent an additional CT scan of the chest or abdomen within 4 wk of PET/CT. Software fusion of PET and CT was performed using a fully automated, intensity-based algorithm. The accuracy of the coregistration of PET and CT scans was evaluated by measuring the distance between landmarks visible in the PET and CT images. Histologic evaluation and follow-up for 6 mo served as the gold standard for the presence or absence of recurrent CRC. RESULTS: On a patient basis, the accuracy of staging was significantly higher for in-line PET/CT than for PET (88% vs. 71%, P = 0.01). Software fusion of the independently acquired PET and CT images was unsuccessful in 8 patients (24%). In the remaining patients, the mean distance between 62 landmarks visible in PET and CT was 12.9 +/- 7.9 mm, whereas it was only 7.7 +/- 4.7 mm for in-line PET/CT (P < 0.001). CONCLUSION: In patients with suspected recurrent CRC, in-line PET/CT significantly improves staging compared with PET alone. Due to its high failure rate, software fusion of independently acquired PET and CT studies cannot be considered to represent an alternative to in-line PET/CT.


Subject(s)
Colorectal Neoplasms/diagnostic imaging , Fluorodeoxyglucose F18 , Image Interpretation, Computer-Assisted/methods , Neoplasm Recurrence, Local/diagnostic imaging , Subtraction Technique , Algorithms , Female , Humans , Male , Middle Aged , Neoplasm Staging/methods , Positron-Emission Tomography/methods , Radiopharmaceuticals , Reproducibility of Results , Retrospective Studies , Sensitivity and Specificity , Software , Tomography, X-Ray Computed/methods
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