[Therapeutic decisions and treatment with sorafenib in hepatocellular carcinoma: final analysis of GIDEON study in Italy]. / Scelte terapeutiche e trattamento con sorafenib nell'epatocarcinoma: analisi finale dello studio GIDEON in Italia.

INTRODUCTION: Sorafenib, an oral multikinase inhibitor, is the only targeted agent approved for the treatment of patients with hepatocellular carcinoma (HCC) after demonstration to increase overall survival compared to placebo in two randomized phase III study. GIDEON (Global Investigation of therapeutic DEcisions in HCC and Of its treatment with sorafeNib) is the largest, global, non-interventional, prospective study of patients with uHCC (n>3200) treated with sorafenib in real-life clinical practice conditions. Here we report the final analysis of safety and efficacy in the Italian cohort of patients. METHODS: Patients with unresectable HCC who are candidates for systemic therapy, and for whom a decision has been made to treat with sorafenib, are eligible for inclusion. Patients demographics disease characteristics and treatment history were recorded at baseline visit. Sorafenib dose, concomitant medications, performance status, liver function, adverse events and efficacy (survival and response rate) were collected throughout the study. RESULTS: In the Italian cohort of the GIDEON study 278 patients were included in 36 centers. The global rate of adverse events was 81%. Drug-related events accounted for 67%, mostly of grade 1 and 2, and only 8% were classified as serious. The most common were diarrhea (24%), fatigue (23%), dermatological (14%), rash/exfoliation (10%), hypertension (9%), hemorrage/bleeding of gastrointestinal tract (6%). Overall survival was 14.4 months and time to progression 6.2 months. Objective responses were observed in 14 patients (5%) with 3 complete responses (1%). Stable diseases of at least 6 weeks were observed in 113 patients (41%) with a 30% of disease control rate. DISCUSSION: The safety profile of sorafenib in terms of rate and type of adverse events is similar to that emerged in the global international GIDEON study as well as in the pivotal registration studies.

Sorafenib therapy for hepatocellular carcinoma in an HIV-HCV coinfected patient: a case report.

BACKGROUND/AIMS: HIV and hepatitis C virus (HCV) share common modes of transmission, resulting in about 33% incidence of coinfection among people infected with HIV. The survival benefit from highly effective antiretroviral therapy (HAART) for HIV infection is resulting in an increased incidence of hepatocellular carcinoma (HCC) in this population. There are no reports to date regarding the coadministration of HAART and sorafenib for hepatocellular carcinoma. METHODS: We report the case of a 42-year-old male patient coinfected with HIV and HCV who developed advanced HCC not amenable to curative therapy. The patient was treated with sorafenib, an oral multikinase inhibitor shown to lead to a longer median survival time and time to progression in patients with advanced HCC. Antiretroviral therapy was continued during sorafenib therapy. RESULTS: The patient achieved a partial tumor response after 3 months and continued to respond at subsequent assessments. His serum alpha-fetoprotein normalized from 2,172 IU/ml to 2 IU/ml. He had durable stable disease after 23 months of therapy. Antiretroviral therapy was efficacious (CD4(+) lymphocyte count, 377/microl; HIV viremia, <50 copies/ml). The simultaneous administration of these therapies was well tolerated. No grade 3 or 4 toxicities were observed. Exacerbation of pre-existing hypertension, grade 2 diarrhea, and grade 1 skin reaction were observed. CONCLUSIONS: This is the first report in which sorafenib has been successfully used to treat HCC in a patient with HIV-HCV coinfection.

Phase III, randomised, multicentre trial of maintenance immunotherapy with low-dose interleukin-2 and interferon-alpha for metastatic renal cell cancer.

This is the first phase III randomised trial to evaluate maintenance immunotherapy in metastatic renal cell cancer (mRCC). Patients were randomised to receive treatment with a 4-week cycle of subcutaneous low doses IL-2 + IFN in months 1, 3 and 5, and then every 3 months until the first documented disease progression (arm A, suspension), or the same regimen, with chronic maintenance of immunotherapy, regardless of tumour response, until death or intolerable toxicity (arm B, maintenance). The primary endpoint was overall survival (OS); secondary endpoints were time from first progression to death (TFPTD) and tolerability. One hundred and eighty-three patients were enrolled between January 1998 and November 2003. After a median follow-up of 53.9 months, response rate, median OS and median TFPTD were 14.7% (6.3% CR) versus 11.3% (5.5% CR), 14 versus 14 months, 6 versus 5 months, in arms A and B, respectively with no significant differences between the groups. Cox regression analysis showed that the use of chemotherapy after first progression (HR 0.54; 95% CI 0.35-0.86; p = 0.008), PS = 0 (HR 0.53; 95% CI 0.35-0.81; p = 0.001) and female gender (HR 0.63; 95% CI 0.41-0.98; p = 0.038) were significantly associated with a longer TFPTD; treatment arm was not significant (HR 0.88; 95% CI 0.60-1.31; p = 0.54). Toxicity was mainly limited to WHO grades 1 or 2. Chronic maintenance immunotherapy after disease progression is feasible, but does not significantly increase OS or the TFPTD.

Anxiety levels in cancer patients and "life sound" experience.

AIMS AND BACKGROUND: For the hospitalized cancer patient, time takes on a rhythm which is very different from the external reality. Based on the idea that time represents a fundamental dimension of human existence and is connected to future plans, time spent waiting and memories, we carried out this experience entitled "Life Sound" project. The objectives of the project were to experiment different and unusual ways of spending time in hospital in order to improve the quality of life of the hospitalized cancer patient, to help the patient adapt to the hospital environment, to encourage awareness of self and to give a different meaning to time spent in the hospital. In particular, we evaluated the reduction in the levels of anxiety, in psychological suffering and the improvement in communication. METHODS: We met with patients, family members, friends, volunteers and department personnel (doctors, psychologists, nurses) in a room in the Oncology and Hematology Department set aside specifically for recreation activities such as having a cup of tea while listening to music, talking, joking, listening to people's memories and celebrating birthdays, anniversaries and other special days. The study, which involved 109 patients, was carried out through the use of the questionnaire STAI-Y distributed before and after the event. RESULTS: The results showed a statistically significant difference in anxiety levels 2 hrs before participation (mean = 38.33) and 2 hrs after participation (mean = 34.77) in the program. This variation was also assessed based on gender, age, cancer stage, time since diagnosis and performance status but did not result in any statistically significant difference. CONCLUSIONS: The "Life Sound" project encourages the emergence of positive feelings, of a renewed willingness to invest in personal and caring relationships, which are connected to the patient's ability to face this illness, and the opening of new channels of communication with family members and hospital staff.