Giuseppe Colloca

Second-line chemotherapy in metastatic docetaxel-resistant prostate cancer: a review.

The results of cytotoxic therapy in the second-line setting of metastatic castration-resistant prostate cancer have demonstrated that disease is poorly controlled after taxane resistance with a time to progression of 3xa0months or less. Many trials of second-line chemotherapy have been disappointing. However, most of patients with docetaxel-pretreated castration-resistant disease receive a second-line chemotherapy. Molecular mechanism of castration resistance and docetaxel resistance is resumed, and clinical trials of second-line chemotherapy after docetaxel progression are reviewed. Reintroduction of docetaxel after a drug-free interval is an active treatment in docetaxel-pretreated patients, and only recently a prospective study documented a survival benefit of 2.4xa0months after second-line taxane-based chemotherapy of metastatic docetaxel-resistant prostate cancer. Although a second-line chemotherapy with a taxane could improve overall survival, a change of biology of castration-resistant prostate cancer after docetaxel is suggested, as inferred by the renewed hormonal sensitivity, whose role on survival remains unknown, and from the activity of antiangiogenic drugs.

Health-related quality of life assessment in prospective trials of systemic cytotoxic chemotherapy for metastatic castration- resistant prostate cancer: which instrument we need?

Knowledge about psychological health of men with prostate cancer is still limited. HRQoL assessment adds value in symptom management by allowing a broader understanding of the impact of symptom management beyond the targeted symptom, on functioning, and on overall QoL. In this paper, the results of the commonly used HRQoL questionnaires in phase III randomized clinical trials of chemotherapy in metastatic castration-resistant prostate cancer has been discussed. An overview about symptom burden, treatments and HRQoL domains, a description of available HRQoL instruments used for patients with metastatic castration-resistant prostate cancer were reported. Finally, the characteristics of most commonly used HRQoL instruments were identified and compared. To provide better empirical justification for the selection of HRQoL instruments, head-to-head comparisons of them within the same studies are needed. Estimating a minimal important difference could be significant when interpreting trial results. The impact of HRQoL scores in clinical practice remains unclear; poor communication of clinical significance of the results and limited training of clinicians are the most important barriers to a widespread use of HRQoL questionnaires.

The Effects of Social Support on Health-Related Quality of Life of Patients with Metastatic Prostate Cancer

Patients with metastatic prostate cancer (PC) live longer than patients with metastatic tumours of other sites. Consequently, their social network can influence their quality of life (QoL) during a remarkable life span. The aim of this article is to present the findings of a systematic review of the studies that focused on social network supporting the quality of life of these patients. A systematic review for studies meeting specific criteria was undertaken on three databases. Some level of unmet psychological needs was present in 54xa0% of the patients. Depression and fatigue are highly prevalent, and the dyads, patient and partner, are at higher risk for distress symptoms. The efforts of individuals to cope with metastatic PC appear influenced by adaptative skills and specific types of family support. Psychological and relational problems predominate in the hormone-sensitive stage and are increasingly replaced by physical symptoms, social and spiritual needs in the later stages. In the early castration-resistant stage, patients will discuss with their doctors information about drugs, control of side effects and treatment strategies. In metastatic PC patients, needs change during the course of the disease. Social support plays a major role in maintaining or disrupting QoL and inxa0the efficacy of psychosocial treatments. The trajectory of disease and its effect on the reduced QoL over the entire life expectancy should be kept in mind by health system providers and social workers.

CA125-related Measures of Tumor Kinetics and Outcome of Patients with Recurrent Ovarian Cancer Receiving Chemotherapy: A Retrospective Evaluation

OBJECTIVEnDefining the reliability of cancer antigen-125-related kinetics criteria versus Gynecologic Cancer Inter Group criteria in predicting the tumor outcome after chemotherapy in patients with recurrent ovarian cancer.nnnMETHODSnA retrospective monoinstitutional assessment of CA125-related versus Gynecologic Cancer Inter Group-related parameters was performed after cytotoxic chemotherapy in patients with metastatic ovarian cancer treated from 2006 to 2011. A correlation analysis between the response and progression measurements has been performed, and the outcome has been reported.nnnRESULTSnAmong 42 eligible patients, tumor response and progression calculated by CA125 kinetics, with tumor response at 8 weeks and specific growth rate at progression, exhibited a significant correlation with progression-free and overall survival, similar to tumor response and progression by Gynecologic Cancer Inter Group criteria.nnnCONCLUSIONSnThe tumor response at 8 weeks higher than 1.77 appears to be a good surrogate of clinical response, whereas the definition of progression when CA125 increases above a value double than the nadir suggests a similar performance of growth rate at progression versus Gynecologic Cancer Inter Group criteria and warrants further investigation.

Analysis of Response-Related and Time-to-event Endpoints in Randomized Trials of Gemcitabine-Based Treatment Versus Gemcitabine Alone as First-Line Treatment of Patients With Advanced Pancreatic Cancer

BACKGROUNDnGemcitabine-based combinations in advanced pancreatic cancer have been reported to have superior activity compared with gemcitabine alone. The results of the commonly used endpoints of clinical trials after chemotherapy or targeted therapy have been poorly reported.nnnMETHODS AND MATERIALSnWe performed a search of randomized trials of systemic treatment that included gemcitabine plus chemotherapy or targeted therapy versus gemcitabine alone. For selected trials, the differences between the treatment arms for every endpoint were calculated, and a correlation analysis between these differences and the differences in overall survival was performed for every intermediate endpoint. Whenever a correlation coefficient was significant, regression analysis was performed. Finally, an analysis was performed to evaluate the factors that could mediate and moderate the effect of progression-free survival on overall survival.nnnRESULTSnIn addition to overall survival, progression-free survival, the overall response rate, and the disease control rate were the most frequently reported endpoints. Of the possible surrogate endpoints of overall survival, progression-free survival appears to be a reliable endpoint to assess chemotherapy (R(2)xa0= 0.646) and chemotherapy plus targeted therapy (R(2)xa0= 0.530) regimens and the disease control rate to assess chemotherapy (R(2)xa0= 0.569). Of the factors that could limit the effect of progression-free survival on overall survival, the interval of radiologic evaluation could play a role.nnnCONCLUSIONnIn the selected trials, progression-free survival and the disease control rate were the most reliable surrogate endpoints of overall survival. Similar to the time-to-event endpoints, a standardization of response-related endpoints is strongly recommended.

Trial-level analysis of progression-free survival and response rate as end points of trials of first-line chemotherapy in advanced ovarian cancer

Progression-free survival (PFS) has been reported as surrogate end point of overall survival (OS) in trials of advanced ovarian cancer (AOC). However, there is not a trial-level evaluation of surrogacy. The aim of this study is to perform an analysis of randomized trials enrolling patients with AOC receiving a first-line systemic chemotherapy, in order to evaluate the results of PFS, the other intermediate end points and their relationship with OS. A literature search of phase 3 randomized trials was performed by a predefined protocol. For each trial, the differences between arms of the results of OS and of other end points were calculated. These differences were compared by Spearman’s rho coefficient to find out the potential correlation between every end point and OS. For the end points with the higher relationships with OS, the proportion of variability explained (R2) was calculated by regression analysis. Thirty-eight studies have been included. PFS appears to be the end point more closely related to OS (R2xa0=xa00.506; pxa0<xa00.001), and this correlation is higher among studies published before 2003. ORR is correlated with OS only in the trials published after 2003 (R2xa0=xa00.344; p 0.027; 14 trials). In conclusion, in more recent trials ORR shows a level of correlation with OS similar to that of PFS. Though PFS should no longer be considered a surrogate end points of OS in trials of patients receiving a first-line chemotherapy for AOC, a prospective evaluation of new response-related end points is strongly recommended.

Erratum to: Role of family history and tumor location on prognosis of patients with colorectal cancer and synchronous metastases

Background/aims nFamily history of colorectal cancer and tumor location along colon-rectum have been reported as prognostic factors. The aim of the current study is to analyze the role of both on overall survival in a series of patients with metastatic colorectal cancer with synchronous metastases.

Incidence and Correlates of Fatigue in Metastatic Castration-Resistant Prostate Cancer: A Systematic Review.

Prostate cancer is the second most common malignancy of men in the western countries. Fatigue is the most stressful symptom of which patients with metastatic castration-resistant prostate cancer (mCRPC) complain. The aim of this article was to report available data about the incidence of fatigue in mCRPC and its correlates. The design involved a systematic review to define incidence of fatigue according to Common Toxicity Criteria in randomized controlled trials of medical treatments of mCRPC and according to International Classification of Diseases Revision 10 (ICD-10) criteria, and to define prevalence and correlates of fatigue in patients with mCRPC. The data source used was PubMed. In December 2014, 2 PubMed searches were performed and the clinical data on the occurrence of cancer-related fatigue along the course of metastatic disease, and findings about its pathogenesis were summarized. Cancer-related fatigue, as defined according to ICD-10 criteria, was reported in 12% to 21% of patients, and prospective clinical trials showed a prevalence of Grade 3/4 fatigue according to Common Toxicity Criteria of 0% to 18%. A list of possible correlates of fatigue in mCRPC, either patient-related, disease-related, or treatment-related, is proposed herein for future studies. Antineoplastic treatments, particularly chemotherapy and radiotherapy, have a major role in the pathogenesis of fatigue in metastatic prostate cancer, however, hormonal treatments remain the most prevalent therapies. A standardized tool for multidimensional assessment of fatigue in metastatic cancer is suggested.

End points of clinical trials in metastatic castration-resistant prostate cancer: A systematic review.

AIMnTo review the definition and performance of the commonly used end points in trials of systemic therapies in metastatic castration-resistant prostate cancer patients.nnnMETHODSnA literature search was undertaken on PubMed database to identify studies meeting established criteria, with the aim of selecting randomized clinical trials and study definition and performance of their end points. The end points were grouped into three categories: overall survival (OS), time-to-event end points, and response end points. A special analysis was performed for secondary end points of the studies which documented a benefit in OS in the experimental arm. Finally, publishes analyses for surrogacy of the included end points were also reported.nnnRESULTSnOS, time-to-event and response end points in 31 selected trials were analyzed. OS was the primary end point in 14 trials, and the secondary end point in 17. A time-to-event end point was the primary end point in 8 studies, and the secondary end point in 22; the most reported time-to-event end points were composite end points, and the events changed among trials. A response end point was the primary end point in 9 studies, in 3 it was prostate-specific antigen (PSA)-related, in 3 pain-related and in 3 mixed. A response end point was the secondary end point in 19 studies: PSA response and radiologic response were the most frequently used secondary end points in 19 and 11 trials, respectively, while pain response was used in 5 studies.nnnCONCLUSIONnA homogeneous definition of progression in future trials is mandatory. Among response end points, pain-response and PSA-response appear to be the most reliable.

Anthracycline-based chemotherapy in metastatic endometrial carcinoma: an update.

The purpose of this review is to analyze clinical evidence about the activity and efficacy of anthracycline‐based chemotherapy in metastatic endometrial cancer and to identify the most important preclinical findings that would address future clinical trials. A literature search of published studies was undertaken. Studies were selected by predefined criteria. Clinical trials and preclinical studies were analyzed. The search identified eight phase 3 and 13 phase 2 clinical trials of patients with metastatic endometrial carcinoma treated with an anthracycline‐based regimen. The planned dose intensity of the anthracycline had no effect on response rates and survival. Survival increased for patients with a good performance status, and sometimes the duration of responses to anthracycline monotherapy can be very long‐lasting. The major findings of anthracycline resistance in preclinical models are reported. Possible future biomarkers targeting mechanisms of anthracycline resistance are suggested, and efforts to define a molecular classification of endometrial cancer are desirable.