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Background: The efficacy and safety of linifanib (ABT-869), a selective inhibitor of vascular endothelial growth factor and platelet-derived growth factor receptor tyrosine kinases, were assessed in this phase 2, single-arm, open-label, multicenter trial., Methods: Eligible patients had unresectable or metastatic hepatocellular carcinoma and had received ≤ 1 prior systemic therapy. Patients received oral linifanib at a fasting dose of 0.25 mg/kg,. The primary endpoint was the progression-free rate at 16 weeks. Tumor response was assessed every 8 weeks. Secondary endpoints included the time to disease progression, overall survival, and objective response rate. Safety was also assessed., Results: Of the 44 patients enrolled, the majority were Asian (89%), had received no prior systemic therapy (82%), had Child-Pugh class A hepatic function (86%), and had hepatitis B virus infection (61%). The estimated progression-free rate at 16 weeks was 31.8% (34.2% for patients with Child-Pugh class A hepatic function), the estimated objective response rate was 9.1% (10.5% for patients with Child-Pugh class A hepatic function), the median time to disease progression was 3.7 months (3.7 months for patients with Child-Pugh class A hepatic function), and the median overall survival was 9.7 months (10.4 months for patients with Child-Pugh class A hepatic function). The most common linifanib-related adverse events were diarrhea (55%) and fatigue (52%). The most common linifanib-related grade 3/4 adverse events were hypertension (25%) and fatigue (14%). Serum levels of biomarkers cancer antigen (CA) 125, cytokeratin fragment (CYFRA)21.1, and protein induced by vitamin K absence or antagonist II (PIVKA) demonstrated potential as prognostic indicators of patient response or outcome., Conclusions: Single-agent linifanib was found to be clinically active in patients with advanced hepatocellular carcinoma, with an acceptable safety profile., (Copyright © 2012 American Cancer Society.)

Background: Intrahepatic arterial yttrium 90 ((90)Y) microspheres have been proposed as a less toxic, less invasive therapeutic option to transhepatic arterial chemoembolization (TACE) for patients with surgically unresectable hepatocellular carcinoma (HCC). TACE has demonstrated the ability to prolong survival. However, long-term survival remains uncertain., Methods: In a 2-cohort experience in the treatment of North American patients who had advanced, unresectable, biopsy-proven HCC, 691 patients received repetitive, cisplatin-based chemoembolization; and a separate cohort of 99 patients who had similar treatment criteria received a planned, single dose of (90)Y. Over the study period, an additional 142 patients were followed without treatment (total, 932 patients)., Results: Overall survival was slightly better in the (90)Y group compared with the TACE group (median survival, 11.5 months vs 8.5 months). However, the selection criteria indicated a small but significant bias toward milder disease in the (90)Y group. By using stratification into a 3-tier model with patients dichotomized according to bilirubin levels <1.5 mg/dL, the absence of portal vein thrombosis (PVT), and low alpha-fetoprotein plasma levels (<25 U/dL), an analysis of survival in clinical subgroups indicated that the 2 treatments resulted in similar survival. In addition, patients who had PVT or high alpha-fetoprotein levels also had similar survival in both treatment groups., Conclusions: Given the current evidence of therapeutic equivalence in survival, (90)Y and TACE appeared to be equivalent regional therapies for patients with unresectable, nonmetastatic HCC.

Background: The objectives of the current study were to assess the rates of sexual dysfunction in patients with hepatocellular carcinoma (HCC) and compare the rates of sexual morbidity with a sample of patients diagnosed with chronic liver disease (CLD) and the general population. It was expected that patients diagnosed with HCC would have a greater prevalence of sexual dysfunction than those diagnosed with CLD and the general population, respectively. Furthermore, those patients who reported a sexual dysfunction would also have a poorer quality of life (QOL)., Methods: Twenty-one men diagnosed with HCC and 23 men diagnosed with CLD completed a battery of questionnaires that included the Sexual History Questionnaire and the Functional Assessment of Cancer Therapy-Hepatobiliary., Results: Results indicated that 41% of patients reported a current sexual problem (29% of HCC patients and 71% of patients with CLD) and 43% met the Diagnostic and Statistical Manual of Mental Disorders-4th edition (DSM-IV) criteria for at least 1 type of sexual dysfunction (25% of patients with HCC and 75% of patients with LD). Of the total sample, 68% reported being diagnosed with a comorbid medical condition or taking a medication that had potential sexual side effects. After eliminating cases with comorbid medical conditions and/or who were taking medications that contributed to sexual morbidity, the rate of sexual problems were found to be similar to that of the general population. Clinically significant differences were found with regard to the QOL. People who were experiencing sexual problems also reported a poorer QOL., Conclusions: Although a large percentage of sexual dysfunction may have been secondary to comorbid medical problems and medications, treatment of the sexual dysfunction is still warranted., (Copyright 2005 American Cancer Society)

Background: The authors used computed tomography (CT) scans to correlate the changes in tumor vascularity, necrosis, and size with response and survival after transcatheter arterial chemoembolization (TACE) in patients with advanced, unresectable, hepatocellular carcinoma (HCC)., Methods: The authors studied 72 patients with biopsy-proven, unresectable HCC and focused on 186 individual tumor masses. A baseline, multiphase, helical CT was performed and at least three follow-up CT scans were performed after treatment by TACE. Tumors were classified as hypervascular or hypovascular and patients were classified as responders or nonresponders based on CT evidence of altered tumor size, tumor necrosis, and the appearance of new tumors. A new scoring system was used to monitor patient response to TACE., Results: Thirty-eight patients were responders and 34 were nonresponders. Patient survival was significantly increased (P = 0.009) in patients who were hypervascular responders. Survival also was increased in hypervascular nonresponders compared with hypovascular nonresponders (P = 0.008) and in hypovascular responders compared with hypovascular nonresponders (P = 0.002). Response to chemoembolization was found to be significantly (P = 0.02) and inversely proportional to tumor size, but the number of tumor foci in an individual patient was not predictive., Conclusions: TACE appears to result in improved survival among HCC patients with hypervascular tumors who responded to therapy. However, even patients classified by CT as hypervascular nonresponders and hypovascular responders have improved survival., (Copyright 2003 American Cancer Society)

Background: Detection of portal vein tumor invasion in patients with hepatocellular carcinoma (HCC) is important in determining therapy and prognosis. Fine-needle aspiration (FNA) of a portal vein thrombus under ultrasound guidance facilitates the distinction of malignant from benign thrombus without resorting to laparotomy. In this study, the FNA findings of 46 patients who underwent this procedure are described., Methods: Cytologic findings of 48 aspirations from 46 patients who underwent percutaneous ultrasound-guided portal vein FNA were reviewed., Results: Twenty-nine of the 46 patients had a prior or concurrent biopsy-confirmed diagnosis of HCC at the time of portal vein FNA. On cytologic review, 39 of the aspirates were positive for malignancy, 6 were negative, and 3 were suspicious. Histologic follow-up of three of the six patients with negative aspirates confirmed bland thrombi in their portal veins. No complications resulted from the FNA procedure. Of the 39 aspirates positive for HCC, 22 were well differentiated, 5 were well to moderately differentiated, 9 were moderately differentiated, and 3 were poorly differentiated. In all except the poorly differentiated tumors, a trabecular cellular arrangement was detected in either smears or cell blocks. The cytologic findings in these aspirates, in general, mirror those found in aspirates of HCC in the liver proper., Conclusions: Portal vein FNA is an effective, well tolerated method for disease staging of patients with HCC. When used as the initial diagnostic procedure, in selected patients, it can provide the diagnosis and staging information simultaneously.

From 1976 to 1988, 63 patients received radiation therapy for primary cancers of the extrahepatic biliary system (eight gallbladder and 55 extrahepatic biliary duct). Twelve patients underwent orthotopic liver transplantation. Chemotherapy was administered to 13 patients. Three patients underwent intraluminal brachytherapy alone (range, 28 to 55 Gy). Sixty patients received megavoltage external-beam radiation therapy (range, 5.4 to 61.6 Gy; median, 45 Gy), of whom nine received additional intraluminal brachytherapy (range, 14 to 45 Gy; median, 30 Gy). The median survival of all patients was 7 months. Sixty patients died, all within 39 months of radiation therapy. One patient is alive 11 months after irradiation without surgical resection, and two are alive 50 months after liver transplantation and irradiation. Symptomatic duodenal ulcers developed after radiation therapy in seven patients but were not significantly related to any clinical variable tested. Extrahepatic biliary duct cancers, the absence of metastases, increasing calendar year of treatment, and liver transplantation with postoperative radiation therapy were factors significantly associated with improved survival.

A 39-year-old white woman with breast cancer, metastatic to her skeleton, developed low back and left lower extremity pain and lower extremity weakness. A bone scan evidenced increased radioisotope activity in her lumbar spine and a computed tomography (CT) scan showed a lesion of the L4 vertebra. Because of myelographic findings of a extradural defect at the L4-5 disc space and the possibility of a herniated disc causing the patient's pain and neurologic deficit in her lower extremities, the patient underwent surgery and a large herniated L4-5 disc was removed. As a consequence, the patient experienced relief of the lower extremity pain and return of strength in her lower extremities. She died a considerable time later from refractory hypercalcemia.

This study investigated the antiemetic properties of four different doses of prochlorperazine (10 mg, 20 mg, 30 mg, 40 mg) when given randomly to patients receiving four cycles of the same dose of cisplatin-based chemotherapy. Prochlorperazine was given to 71 patients by slow intravenous infusion 30 minutes before and 3 and 6 hours after the start of cisplatin chemotherapy. The higher doses of prochlorperazine proved to be effective in the control of cisplatin-induced emesis. For the 20 patients who completed all 4 study cycles of treatment, a relationship was discerned between the dose of prochlorperazine administered and the antiemetic effect. When all 71 patients were analyzed in terms of the results of the first cycle of chemotherapy, a significant dose-response effect was also found. Overall toxic reactions in 82 treatment cycles using either 30 mg or 40 mg of prochlorperazine were dystonia (1 patient), restlessness (2), hypotension (3), and drowsiness (12). This study demonstrates that higher-than-conventional doses of prochlorperazine have an impressive antinauseant effect with only moderate toxicity.

The induction of cancer by chemicals as presently understood involves a series of steps, some of which require the passage of time. Many substances that are potent carcinogens in experimental animals are known to exist in nature and occur as part of the human diet. In addition, many of the substances that are known to inhibit experimental carcinogenesis also exist in the human diet. Thus, in addition to industrially produced carcinogens, humans can be presumed to have evolved in an environment that contains both carcinogens and anti-carcinogens. There is also a great deal of experimental and human epidemiologic data on the influence of lipids, proteins and carbohydrates on cancer incidence rates; however, much of those data are confusing and conflicting.