Andrea Saini

Prognostic Role of Vitamin D Status and Efficacy of Vitamin D Supplementation in Cancer Patients: A Systematic Review

BACKGROUND Whether or not hypovitaminosis D can influence the prognosis of cancer patients and whether or not vitamin D (vitD) supplementation improves outcome remain controversial. DESIGN Studies evaluating the prognostic role of vitD and vitD receptor (VDR) in cancer patients and trials evaluating the efficacy of vitD administration on patient outcome were identified by a search of MEDLINE, EMBASE, ISI Web of Knowledge, and the Cochrane Library through June 2010. RESULTS Twenty-five studies were included. A negative prognostic role for low serum vitD level was observed in five cohort studies including patients with breast cancer (one study), colon cancer (two studies), prostate cancer (one study), and melanoma (one study), but not in two studies on non-small cell lung cancer and one study on breast cancer. Three of four studies showed that VDR(+) tumors carry a better prognosis than VDR(-) tumors, whereas VDR polymorphisms were significantly associated with prognosis in five of 10 studies. A significant interaction between serum vitD level and VDR polymorphism was observed in one study. Three randomized trials involving advanced prostate cancer patients explored the prognostic role of vitD supplementation. A meta-analysis of these trials showed no effect on survival (pooled risk ratio, 1.07; 95% confidence interval, CI, 0.93-1.23), with strong heterogeneity among studies. CONCLUSION Hypovitaminosis D seems to be associated with a worse prognosis in some cancers, but vitD supplementation failed to demonstrate a benefit in prostate cancer patients. The currently available evidence is insufficient to recommend vitD supplementation in cancer patients in clinical practice.

Psychological distress in men with prostate cancer receiving adjuvant androgen-deprivation therapy

OBJECTIVES To compare the occurrence of depression, anxiety, self body image perception, sleep disturbances, and diminished quality of life in prostate cancer patients undergoing adjuvant androgen-deprivation therapy (ADT) as opposed to patients in follow-up alone. METHODS AND MATERIALS Hospital Anxiety and Depression Scale, Pittsburgh Sleep Quality Index, Restless Legs Syndrome Study Group essential diagnostic criteria, Body Image Scale and Functional Assessment of Cancer Therapy Prostate were administered to consecutive prostate cancer patients who underwent radical prostatectomy or radiation therapy and are presently either under adjuvant ADT or included in a follow-up program. RESULTS Of the 103 patients enrolled, 49 (47.6%) were receiving adjuvant ADT and 54 (52.4%) were not. Compared with the controls, the patients undergoing ADT showed higher levels of depression (P = 0.002), worse self body image perception (P = 0.001), worse quality of life (P = 0.0001) and worse sleep quality (P = 0.04). ADT was significantly associated with depression at multivariate analysis after adjustment for age, stage, Gleason score, as well as demographic and social variables (P = 0.001). Depression scores showed a strong inverse correlation with quality of life scores (P < 0.01). CONCLUSIONS Adjuvant ADT is associated with depression, worse quality of life, and altered self body image in prostate cancer patients.

Effects of Serum Testosterone Levels After 6 Months of Androgen Deprivation Therapy on the Outcome of Patients With Prostate Cancer

BACKGROUND Controversy exists about whether testosterone serum levels at a cutoff point of < 50 ng/dL during luteinizing hormone-releasing hormone analogue (LHRHA) treatment are related to the outcome of patients with prostate cancer. We assessed the relationship between serum testosterone levels after 6 months of LHRHA therapy and disease outcome in a consecutive series of patients with prostate cancer. PATIENTS AND METHODS Serum testosterone levels were measured prospectively in a cohort of patients given LHRHA for 6 months. End points were time to progression (TTP) and overall survival (OS). RESULTS The study population was 153 patients: 54 with metastatic disease and 99 with biochemical failure. In multivariate analysis, adjustment for age, baseline serum prostatic specific antigen (PSA) levels, Gleason score, and disease stage, testosterone levels < 50 ng/dL failed to be associated with TTP and OS. A cutoff of < 20 ng/dL was associated with a nonsignificant lower risk of progression (adjusted hazard ratio [HR] 0.58; 95% confidence interval [CI] 0.30-1.15; P = .12) and a significant lower risk of death (adjusted HR, 0.19; 95% CI, 0.04-0.76; P = .02). Only 25 patients attained serum testosterone levels < 20 ng/dL. Using a receiver operating characteristic curve (ROC), we found that a testosterone value of 30 ng/dL offered the best overall sensitivity and specificity for prediction of death. Serum testosterone levels < 30 ng/mL were associated with a significantly lower risk of death (adjusted HR, 0.45; 95% CI, 0.22-0.94; P = .034. CONCLUSIONS Serum testosterone levels lower than the currently adopted cutoff of 50 ng/dL have a prognostic role in patients with prostate cancer receiving LHRHA and are a promising surrogate parameter of LHRHA efficacy.

The role of haemoglobin level in predicting the response to first-line chemotherapy in advanced colorectal cancer patients

The purpose of the study was to evaluate the influence of baseline haemoglobin level in predicting response to 5-fluorouracil (5FU)-based first-line chemotherapy in advanced colorectal cancer patients. Data from 631 patients were collected from three different institutions. Globally, overall response rate was 35.8% (226 out of 631). Factors influencing response rate were 5FU dose intensity (high: 43.1%, low: 34.0%, P=0.03); oxaliplatin (yes: 45.8%, no: 22.9%, P<0.0001), performance status (PS 0: 46.1%, 1: 28.8%, 2: 26.7%, P<0.0001), and haemoglobin levels (⩾12 g dl−1: 40.4%, <12 g dl−1: 29.2%, P=0.004). In subgroup analysis significant differences in response rate between anaemic and nonanaemic patients were recorded in those patients treated with infusional chemotherapies (45.7 vs 25.5%, P<0.0001), with high 5FU dose intensity (50.3 vs 32.7%, P=0.005), with PS=0 (49.8 vs 37.9%, P=0.03), and with liver metastases (44.8 vs 33.8%, P=0.002), whereas no difference was evident in those subjects treated with bolus schedules or according to gender. Anaemia was a strong predictor for activity of first-line 5FU-based chemotherapy especially in those groups that showed the best responses, for example high performance status, infusionally treated, higher 5FU dose and those with liver secondaries. Patients with higher haemoglobin levels recorded a greater response rate and a longer time to progression and survival than anaemic subjects. Prospective evaluation of role of correcting anaemia on response to therapy is justified by these results.

Candida albicans and HIV-1 infection.

Candida albicans virulence is in part mediated by fibronectin (FN) interaction. We compared the adherence level to FN (using Becton Dickinson FN‐coated plates) of several strains of yeast isolated from HIV‐1 infected or uninfected subjects affected by candidiasis (30 strains from HIV+ subjects and 18 from HIV− subjects). More adhesive strains were found in HIV+ patients than in HIV− subjects. In particular a mean increase of 120 per cent as regards the total number of adhesive cells and 230 per cent as regards the adhesive cells producing germ tubes was detected in the former group of strains as compared to the latter ( p < 0·001 in both cases). The enhancement of FN expression induced by HIV‐1 infection, as we have previously demonstrated, can increase interest in the adherence to FN of C. albicans strains isolated from AIDS‐affected patients. Moreover, we also underline the important role played by HIV Nef protein in increasing the C. albicans aggressiveness. In fact a significant inhibitory effect of Nef on the phagocytosis of this yeast by macrophages has been demonstrated and the oxidative processes of these cells seem to be down‐regulated by this protein. Copyright

Metronomic Therapy Concepts in the Management of Adrenocortical Carcinoma

Metronomic chemotherapy is the administration of cytotoxic drugs at low doses, on a frequent or continuous schedule, with no extended interruption. This treatment approach can target tumor cells indirectly since it can affect the endothelium of the growing tumor vasculature and stimulates the anticancer immune response. Both the antiangiogenetic and the immunomodulatory roles of metronomic chemotherapy favor a tumor dormancy, a condition that may improve the patient outcome. Prospective clinical trials conducted in several malignancies have shown that metronomic chemotherapy can obtain disease stabilization or responses in tumors that had been made resistant in vivo to conventional chemotherapeutic regimens. Three prospective phase II trials have been conducted in patients with adrenocortical carcinoma (ACC). In all of them, patients heavily pretreated with conventional chemotherapy and mitotane have been enrolled. One trial tested the activity of the association of gemcitabine and fluoropyrimidines administered on a metronomic schedule. In this trial, 40% of patients attained a disease stabilization or disease response that was long lasting in some of them. In the remaining two trials, metronomic chemotherapy was administered in association with antiangiogenetic drugs, and the results were disappointing since no response or stable disease was obtained. In conclusion, metronomic chemotherapy can delay tumor progression in advanced ACC and deserves to be further tested. The concomitant administration of antiangiogenetic drugs may be detrimental. Several important questions remain to be addressed such as the optimal dose and most effective dosing interval, when to use the metronomic approach in the natural history of the disease, the choice of cytotoxic drugs, and the most efficacious way to integrate metronomic chemotherapy with standard therapy protocols.

Recall inflammatory skin reaction after use of pegylated liposomal doxorubicin in site of previous drug extravasation

However, extravasation of pegylated liposomal doxorubicin is generally accompanied by a mild cutaneous reaction that is reversible in a few days. 2 Here, we describe a severe, recall cutaneous reaction to pegylated doxorubicin in a site of previous drug extravasation after the resumption of treatment. A 58-year-old woman with platinum-resistant ovarian cancer was treated at our institution with pegylated liposomal doxorubicin. She had received bilateral oophorectomy and hysterectomy for stage IIIC ovarian cancer with macroscopic residual disease in the peritoneum, the retrocrural lymph nodes, and the retroperitoneum. Use of six cycles of first-line chemotherapy with carboplatin (area under curve [AUC] 6) and paclitaxel (175 mg/m 2 ) on day 1 every 21 days gave a partial response. The disease progressed for the next 5 months, after which she received second-line chemotherapy with topotecan (1·5 mg/m 2

Alberta Breakthrough Pain Assessment Tool: A validation multicentre study in cancer patients with breakthrough pain

Cancer‐related breakthrough pain (BTP) is a common and quite challenging pain syndrome, with significant impact on quality of life. To date, no widely recognized and validated tool for the diagnosis and evaluation of BTP exists. The Alberta Breakthrough Pain Assessment Tool (ABPAT) underwent a validation process during its development, but no experience of its implementation in clinical practice has been reported.

Circadian variation of breakthrough pain in cancer patients

Breakthrough cancer pain (BTP) can place physical, psychological and economic burdens on patients and their productive life. By preventing instead of treating BTP after it occurs, the efficacy of analgesic treatment in cancer patients could be maximized. With this study, we investigated circadian variations in the occurrence of BTP events in cancer patients.

Pharmacoeconomic comparison between chronochemotherapy and FOLFOX regimen in the treatment of patients with metastatic colorectal cancer: A cost-minimization study

Aims and background The addition of oxaliplatin to the widely employed De Gramont schedule (FOLFOX regimen) in patients with metastatic colorectal cancer improved their outcome with a moderate toxicity pattern. The adaptation of the delivery rate of 5-fluorouracil, leucovorin and oxaliplatin to circadian rhythms (chronotherapy) resulted in a very high drug tolerability with clinical results at least comparable to those achieved with the FOLFOX regimen. However, chronomodulated infusion seemed to be more expensive, requiring dedicated electronic pumps and several disposable materials. The present study aimed to compare the direct costs of the two regimens and to determine whether chronotherapy was effectively more expensive than the FOLFOX regimen. Study design The direct costs of drug delivery devices derived from various publicly available sources and of toxicity management as extrapolated from two published studies considering comparable patient subsets were added and compared. Results Pump, central venous system and disposable materials for a single chronotherapy cycle were € 193 or € 212 according to whether the pumps were bought or rented, compared to € 58 for the FOLFOX regimen. Toxicity management costs were € 144 vs € 288 for the two schemes, respectively. Globally, a single course of chronotherapy cost € 337 or € 356, whereas a single FOLFOX cycle cost € 346. Conclusions Direct costs for a single chronotherapy cycle appeared to be comparable to a single course of the FOLFOX regimen. In fact, the major material cost of chronochemotherapy devices was balanced by a better tolerability profile. The overall improvement in quality of life with chronochemotherapy affecting indirect costs, such as reduction of work, and intangible costs is worthy of further pharmacoeconomic attention.