Lucia Fratino

Comprehensive Geriatric Assessment Adds Information to Eastern Cooperative Oncology Group Performance Status in Elderly Cancer Patients: An Italian Group for Geriatric Oncology Study

PURPOSE To appraise the performance of Comprehensive Geriatric Assessment (CGA) in elderly cancer patients (> or = 65 years) and to evaluate whether it could add further information with respect to the Eastern Cooperative Oncology Group performance status (PS). PATIENTS AND METHODS We studied 363 elderly cancer patients (195 males, 168 females; median age, 72 years) with solid (n = 271) or hematologic (n = 92) tumors. In addition to PS, their physical function was assessed by means of the activity of daily living (ADL) and instrumental activities of daily living (IADL) scales. Comorbidities were categorized according to Satarianos index. The association between PS, comorbidity, and the items of the CGA was assessed by means of logistic regression analysis. RESULTS These 363 elderly cancer patients had a good functional and mental status: 74% had a good PS (ie, lower than 2), 86% were ADL-independent, and 52% were IADL-independent. Forty-one percent of patients had one or more comorbid conditions. Of the patients with a good PS, 13.0% had two or more comorbidities; 9.3% and 37.7% had ADL or IADL limitations, respectively. By multivariate analysis, elderly cancer patients who were ADL-dependent or IADL-dependent had a nearly two-fold higher probability of having an elevated Satarianos index than independent patients. A strong association emerged between PS and CGA, with a nearly five-fold increased probability of having a poor PS (ie, > or = 2) recorded in patients dependent for ADL or IADL. CONCLUSION The CGA adds substantial information on the functional assessment of elderly cancer patients, including patients with a good PS. The role of PS as unique marker of functional status needs to be reappraised among elderly cancer patients.

Prevalence of functional disability among elderly patients with cancer

This study is part of a larger multicenter prospective study conducted in Italy to assess the efficacy of the comprehensive geriatric assessment (CGA) among elderly patients with cancer (i.e. aged 65 years or older). The prevalence of functional limitations, and its association with selected characteristics, was investigated among 303 elderly patients consecutively admitted at the Department of Medical Oncology, IRCCS Centro di Riferimento Oncologico, Aviano (Northeast Italy), between 1995 and 1998. These patients had a median age of 72 years (range, 65-94), and were affected by haematological (n=182) or solid tumours (n=121). At baseline, their physical function was assessed, in addition to performance status (PS), by means of the activity of daily living (ADL) and the instrumental activities of daily living (IADL) scales. Overall, 17% of the patients had a limitation for ADL, and 59% for IADL, the prevalence of functional disabilities increased with age. Specifically, 8% of patients had continence limitations and 13% had limitations in taking the prescribed drugs. By multivariate analysis, a poor PS turned out to be a strong independent determinant of both ADL and IADL disabilities.

Modulated Chemotherapy According to Modified Comprehensive Geriatric Assessment in 100 Consecutive Elderly Patients with Diffuse Large B-Cell Lymphoma

Chemotherapy is associated with toxicity in elderly patients with potentially curable malignancies, posing the dilemma of whether to intensify therapy, thereby improving the cure rate, or de-escalate therapy, thereby reducing toxicity, with consequent risks for under- or overtreatment. Adequate tools to define doses and combinations have not been identified for lymphoma patients. We conducted a prospective trial aimed to evaluate the feasibility and efficacy of chemotherapy modulated according to a modified comprehensive geriatric assessment (CGA) in elderly (aged ≥70 years) patients with diffuse large B-cell lymphoma (DLBCL). In June 2000 to March 2006, 100 patients were stratified using a CGA into three groups (fit, unfit, and frail), and they received a rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone modulated in dose and drugs according to comorbidities and activities of daily living (ADL) and instrumental ADL scores. Treatment was associated with a complete response rate of 81% and mild toxicity: grade 4 neutropenia in 14%, anemia in 1%, and neurological and cardiac toxicity in 2% of patients. At a median follow-up of 64 months, 51 patients were alive, with 5-year disease-free, overall, and cause-specific survival rates of 80%, 60%, and 74%, respectively. Chemoimmunotherapy adjustments based on a CGA are associated with manageable toxicity and excellent outcomes in elderly patients with DLBCL. Wide use of this CGA-driven treatment may result in better cure rates, especially in fit and unfit patients.

Clinical Outcomes of Castration-resistant Prostate Cancer Treatments Administered as Third or Fourth Line Following Failure of Docetaxel and Other Second-line Treatment: Results of an Italian Multicentre Study

BACKGROUND The availability of new agents (NAs) active in patients with metastatic castration-resistant prostate cancer (mCRPC) progressing after docetaxel treatment (abiraterone acetate, cabazitaxel, and enzalutamide) has led to the possibility of using them sequentially to obtain a cumulative survival benefit. OBJECTIVE To provide clinical outcome data relating to a large cohort of mCRPC patients who received a third-line NA after the failure of docetaxel and another NA. DESIGN, SETTING, AND PARTICIPANTS We retrospectively reviewed the clinical records of patients who had received at least two successive NAs after the failure of docetaxel. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The independent prognostic value of a series of pretreatment covariates on the primary outcome measure of overall survival was assessed using Cox regression analysis. RESULTS AND LIMITATIONS We assessed 260 patients who received one third-line NA between January 2012 and December 2013, including 38 who received a further NA as fourth-line therapy. The median progression-free and overall survival from the start of third-line therapy was, respectively, 4 mo and 11 mo, with no significant differences between the NAs. Performance status, and haemoglobin and alkaline phosphatase levels were the only independent prognostic factors. The limitations of the study are mainly due its retrospective nature and the small number of patients treated with some of the sequences. CONCLUSIONS We were unable to demonstrate a difference in the clinical outcomes of third-line NAs regardless of previous NA therapy. PATIENT SUMMARY It is debated which sequence of treatments to adopt after docetaxel. Our data do not support the superiority of any of the three new agents in third-line treatment, regardless of the previously administered new agent.

Real-world cabazitaxel safety: the Italian early-access program in metastatic castration-resistant prostate cancer.

AIM Cabazitaxel is a novel taxane that is approved for use in metastatic castration-resistant prostate cancer based on the Phase III TROPIC study, which showed improved overall survival with cabazitaxel/prednisone versus mitoxantrone/prednisone. A global early-access program was initiated in order to provide early access to cabazitaxel in docetaxel-pretreated patients and to obtain real-world data. PATIENTS & METHODS We report interim safety results from an Italian prospective, single-arm, multicenter, open-label trial of 218 patients receiving cabazitaxel 25 mg/m2 every 3 weeks plus prednisolone 10 mg/day, until disease progression, unacceptable toxicity, investigators decision or death. RESULTS Patients completing treatment received a median of six cabazitaxel cycles. The most common grade 3/4 adverse events were neutropenia (33.9%), leukopenia (15.6%), anemia (6%) and asthenia (6%). No peripheral neuropathy or nail disorders were observed. CONCLUSION These results confirm that cabazitaxel has a manageable safety profile in daily clinical practice and support its use in patients with prostate cancer who progress during or after a docetaxel-based therapy.

De novo malignancies after organ transplantation: focus on viral infections.

Organ transplantation is an increasingly used medical procedure for treating otherwise fatal end stage organ diseases with 107,000 transplants performed worldwide in 2010. Newly developed anti-rejection drugs greatly helped to prolong long-term survival of both the individual and the transplanted organ, and they facilitate the diffusion of organ transplantation. Presently, 5-year patient survival rates are around 90% after kidney transplant and 70% after liver transplant. However, the prolonged chronic use of immunosuppressive drugs is well known to increase the risks of opportunistic diseases, particularly infections and virus-related malignancies. Although transplant recipients experience a nearly 2-fold elevated risk for all types of de-novo cancers, persistent infections with oncogenic viruses - such as Kaposi sarcoma herpes virus, high-risk human papillomaviruses, and Epstein-Barr virus - are associated with up to 100-fold increased cancer risks. This review, focusing on kidney and liver transplants, highlights updated evidences linking iatrogenic immunosuppression, persistent infections with oncogenic viruses and cancer risk. The implicit capacity of oncogenic viruses to immortalise infected cells by disrupting the cell-cycle control can lead, in a setting of induced lowered immune surveillance, to tumorigenesis and this ability is thought to closely correlate with cumulative exposure to immunosuppressive drugs. Mechanisms underlying the relationship between viral infections, immunosuppressive drugs and the risk of skin cancers, post-transplant lymphoproliferative disorders, Kaposi sarcoma, cervical and other ano-genital cancers are reviewed in details.

Treatment of non-hodgkin's lymphoma in the elderly : An update

Recent studies specifically directed toward assessing the outcome of older patients with non‐Hodgkins lymphoma (NHL) indicate that age per se is an important and independent prognostic factor for response and survival. We report a review of the clinical trials of the literature and the Aviano Group experience in the treatment of NHL in the elderly. Prospective studies have addressed therapeutic approaches in these patients. Direct comparison of trial results is difficult since different age limits were set for the inclusion of patients under study. These studies suggest that older patients with aggressive NHL should be treated with curative intent. Copyright

Epidemiology of de novo malignancies after solid-organ transplantation: Immunosuppression, infection and other risk factors

Organ transplantation is an increasingly used medical procedure for treating otherwise fatal end-stage organ diseases, and a large number of anti-rejection drugs have been developed to prolong long-term survival of both the individual and the transplanted organ. However, the prolonged use of immunosuppressive drugs is well known to increase the risk of opportunistic diseases, particularly infections and virus-related malignancies. Although transplant recipients experience a nearly twofold elevated risk for all types of de novo cancers, persistent infections with oncogenic viruses are associated with up to hundredfold increased risks. Women of the reproductive age are growing in number among the recipients of solid-organ transplants, but specific data on cancer outcomes are lacking. This article updates evidences linking iatrogenic immunosuppression, persistent infections with oncogenic viruses, other risk factors and post-transplant malignancies. Epidemiological aspects, tumourigenesis related to oncogenic viruses, clinical implications, as well as primary and secondary prevention issues are discussed to offer clinicians and researchers alike an update of an increasingly important topic.

Hormone therapy in elderly breast cancer patients with comorbidities

Life-expectancy and comorbid conditions must be considered in the process of treatment decision-making for elderly patients affected by breast cancer both in the adjuvant and metastatic settings. Moreover, the choice of adjuvant treatment in all age groups is based on two main points: endocrine responsiveness and risk of relapse without setting an upper age limit. The hormonal therapeutic armamentarium of the medical oncologist is now open to different options that may best be tailored to different clinical situations, particularly in elderly women.

safety and clinical outcomes of patients treated with abiraterone acetate after docetaxel: results of the Italian Named Patient Programme

To assess the safety and efficacy of abiraterone acetate (AA) in patients with metastatic castration‐resistant prostate cancer (mCRPC) treated in a compassionate named patient programme (NPP).