Rossella Fisichella

Clinical Presentation and Outcome of Colorectal Cancer in HIV-Positive Patients: A Clinical Case-Control Study

Background: Data on colorectal cancer (CRC) in HIV-positive patients are limited. The study objective was to investigate and compare clinical presentation and outcome between HIV-positive and HIV-negative CRC patients. Patients and Methods: Between September 1985 and November 2003 we identified 27 cases of HIV-positive CRC patients from the cancer registry database – Italian Cooperative Group AIDS and Tumours (GICAT); the clinical presentation/outcome information was retrieved. Each HIV-positive patient from our institution was randomly matched (ratio 1:2) with HIV-negative patients (54 controls) based on age, sex, and year of diagnosis in the same time period. Differences in clinical presentation, treatment, and overall survival were assessed. Results: Of 1130 HIV-negative CRC patients, 54 were identified and matched with 27 HIV-positive patients. Compared with the HIV-negative patients, the HIV-positive patients had a higher risk of lower performance status (PS: ≥2) (odds ratio (OR) = 14.4; 95% confidence interval (CI): 3.6–57.7), a higher risk of unfavorable Dukes’ stage (D) (OR = 4.9; 95% CI: 1.8–13.5), and a higher risk of poor grading (G3–G4) (OR = 5.0; 95% CI: 1.9–13.4). Median overall follow-up was 27 months (range: 2–212). At multivariate analysis, the only characteristics that significantly reduced the survival of the CRC patients were: HIV-positive status (hazard ratio (HR): 2.4; 95% CI: 1.1–5.2) and Dukes’ stage D (HR: 3.7; 95% CI: 1.9–7.1). Conclusion: Our data show that HIV-positive CRC patients compared to HIV-negative patients have a poorer PS, an unfavorable Dukes’ stage, higher grading and shorter survival.

Anal Cancer: Focus on HIV-Positive Patients in the HAART Era

Anal cancer represents an increasing health problem, especially in immune-compromised patients, as HIV-positive patients. Notably, a significant higher incidence rate is reported among HIV infected patients with the advent of highly active antiretroviral therapy (HAART). To date, no randomised trial supports the correlation between existing screening strategies and reduced progression of anal intraepithelial neoplasia (AIN) to anal cancer or improved survival. Nevertheless, screening and treatment of AIN by topical agents should be implemented in high risk population. Data on invasive anal cancer treatment show that combined modality treatment (CMT) is the treatment of choice. Early reports on HIV-positive patients describe higher treatment toxicity and a relation with lower CD4 count and higher HIV viral load. More recently, reported outcomes seem to be similar in HIV-positive population and general population. Reports on a rise in local recurrence rates and in acute side effects along with a correlation with pre-treatment CD4 counts in HIV-positive patients, are not confirmed by all authors. The development of the first approved vaccine is a milestone in the field of anogenital cancers. However, many questions are still unresolved especially as concerns immunization in the setting of HIV infection.

Oxaliplatin Based Chemotherapy and Concomitant Highly Active Antiretroviral Therapy in the Treatment of 24 Patients with Colorectal Cancer and HIV Infection

BACKGROUND Although FOLFOX4 is considered the standard chemotherapy regimen for colorectal cancer (CRC), few data are available on its results in human immunodeficiency (HIV)-related CRC. The results were analyzed to evaluate feasibility and activity of FOLFOX4 plus highly active antiretroviral therapy (HAART) in metastatic CRC (mCRC) HIV-seropositive patients. PATIENTS AND METHODS From January 2002 to March 2007, 24 patients were selected among the CRC HIV-seropositive patients treated with FOLFOX4 and concomitant HAART within the Italian Cooperative Group on AIDS and Tumors (GICAT). RESULTS Four median cycles of chemotherapy were administered; the most common severe toxicity was neutropenia (37.5%). An overall response rate of 50% was observed; 4.2% of patients achieved complete response and 45.8% partial response. No opportunistic infections occurred during or immediately after chemotherapy. The median CD4+ count was 380 (range 220-570) at diagnosis. CONCLUSIONS To our knowledge, this is the largest study describing activity and tolerability of FOLFOX4 and HAART, in this setting. FOLFOX4 plus concomitant HAART resulted feasible and active also in HIV-seropositive patients. Moreover, the concomitant use of HAART did not to seem to increase the FOLFOX4 toxicity. This study suggests the good tolerability of the FOLFOX4, making it a reasonable option for combination with HAART.

FOLFOX4 in the treatment of metastatic colorectal cancer in elderly patients: A prospective study

Elderly patients constitute a subpopulation with special characteristics that differ from those of the general population and have been under-represented in clinical trials. We, prospectively, analyzed the toxicity and efficacy of the original FOLFOX4-regimen in the treatment of elderly patients affected by metastatic (m) colorectal cancer (CRC). Thirty-six consecutive patients aged 67-82 years (median age 72 years), 22 males and 14 females, with mCRC and measurable disease, were enrolled in the study. The primary site of metastases was the liver (36.1% of patients). The median ECOG Performance Status (PS) was 1. The main hematological and extra-hematological (grade 3 or 4) toxicities were neutropenia (38.9%) and neurological (13.9%), respectively. A total of 36 patients, aged 67-82 years were included. Twenty-two and 14 patients were male and female, respectively. The median age was 72 years (range 67-82). The primary site of metastases was the liver (36.1% of patients). The median ECOG Performance Status (PS) was 1. The overall response rate (ORR) was 44.4% and similar to original study. Median progression-free survival (PFS) was 7.5 months and median overall survival (OS) was 16 months. The main hematological and extra-hematological (grade 3 or 4) toxicities were neutropenia (38.9%) and neurological (13.9%), respectively. Tolerability, however, was manageable and no toxic death occurred. FOLFOX4-regimen maintains its efficacy, and safety ratio in elderly patients with mCRC and good performance status. It would be considered the treatment of choice in the treatment of this particular setting of patients.

Prognostic and predictive response factors in colorectal cancer patients: Between hope and reality

Colorectal cancer (CRC) represents one of the most commonly diagnosed cancers worldwide. It is the second leading cause of cancer death in Western Countries. In the last decade the survival of patients with metastatic CRC has improved dramatically. Due to the advent of new drugs (irinotecan and oxaliplatin) and target therapies (i.e., bevacizumab, cetuximab and panitumab), the median overall survival has risen from about 12 mo in the mid nineties to 30 mo recently. Many questions needing of right collocations and more clearness still exist regarding the prognostic factors and the predictive factors of response to therapy. Despite advances in dosing and scheduling of chemotherapy in both adjuvant and advanced settings, and a greater emphasis on early detection, the outlook still remains poor for most patients. Molecular analyses have shown that the natural history of all CRCs is not the same. Individual patients with same stage tumours may have different long term prognosis and response to therapy. In addition, some prognostic variables are likely to be more important than others. Here we review the role of prognostic factors and predictive factors according to the recently published English literature.

Safety and efficacy of radiotherapy treatment in elderly patients with localized prostate cancer: A retrospective analysis

The purpose of this study was to evaluate the feasibility and the activity of radiotherapy treatment in patients aged ≥75 with prostate cancer (PC). From January 2000 to December 2007, 107 consecutive patients aged ≥75 years received radiotherapy with radical intent for PC. Eighty-one patients received radiotherapy in combination with a 6 months androgen suppression therapy. Variables considered were age, stage, co-morbidities according to the adult co-morbidity evaluation index (ACE-27) and performance status (PS). The median age was 79.1 years (range 76-87). The 23.4% of patients showed no co-morbidities, while the 46.7% had mild, 23.4% moderate, and 6.5% severe co-morbidities, respectively. All patients completed the planned radiation treatment. At a median follow-up of 37.8 months, the 5-year overall survival rate was 78%. There was a better survival for patients with no or mild co-morbidities (p<0.0001) and a good PS (p=0.009). The actuarial disease-free survival at 60 months was 75.8%. Difference in acute and late toxicity rate was detected between ACE-27 classes for diarrhea and marginally for urinary toxicity, but no difference was detected for different age. We conclude that compliance with radiotherapy is good and rate of toxicity is acceptable in elderly patients. Increasing severity of co-morbidity may sufficiently shorten remaining life expectancy to cancel gains with radical radiotherapy. Further prospective trials are needed to confirm these results.

Localized and systemic bacterial infections in necrotizing pancreatitis submitted to surgical necrosectomy or percutaneous drainage of necrotic secretions

BackgroundInfectious complications are observed in 40-70% of all patients with severe acute pancreatitis. Infections are associated with a significant increase in mortality rates.MethodsWe evaluated the prevalence and characteristics of pancreatic and systemic infections in 46 patients with necrotizing pancreatitis submitted to surgical procedures during their hospital stay as well as the impact of such infectious complications on patient clinical outcome. Samples for microbiological cultures were taken at hospital admission from blood and bile and 2 days after invasive procedure from blood, drainage fluid, bile and necrotic tissues.Results74% patients with necrotizing pancreatitis had a localized or systemic infection. At admission, 15% of subjects had positive blood cultures whereas 13% had evidence of bacterial growth from bile cultures. Two days after the invasive procedures for removal of necrotic materials and fluids, blood cultures became positive in 30% of patients in spite of antibiotic prophylaxis and bile cultures resulted positive in 22% of cases. Furthermore, bacterial growth from drainage fluids was found in 30% and from homogenized necrotic material in 44% of cases. As refers to bacterial isolates, all patients had a monomicrobial infection. Carbapenems were the drugs with the best sensitivity profile.Mortality rate was significantly (p < 0.05) higher among patients with infection (17%) than subjects without infection (8%). Within the infected group, those subjects with evidence of systemic infection (positive blood cultures) developed more complications and demonstrated a higher (p < 0.05) mortality rate (28%) than those who had only a localized infection (10%).ConclusionsInfectious complications significantly increase mortality in patients with necrotizing pancreatitis. In addition, subjects with systemic infections developed more complications and demonstrated a higher mortality rate in comparison with those having a localized infection. In our study, the sensitivity pattern of the isolated microorganisms suggests to consider carbapenems as the best option for empirical treatment in patients with necrotizing pancreatitis who develop a clear-cut evidence of systemic or localized bacterial infection.

Oxaliplapin and Capecitabine (XELOX) Based Chemotherapy in the Treatment of Metastatic Colorectal Cancer: The Right Choice in Elderly Patients

PURPOSE Elderly patients with metastatic colorectal cancer (mCRC) differ from the general population and are underrepresented in clinical trials. We, retrospectively, analyzed the safety and efficacy of XELOX regimen in the treatment of elderly patients affected by mCRC. PATIENTS AND METHODS One-hundred-eleven consecutive patients, aged 70 years or older, were enrolled in the study. RESULTS All patients were evaluated for safety and efficacy (male/female, 63/48). Median age was 75 years (range 71-85 years). Median Eastern Cooperative Oncology Group Performance Status (ECOG PS) was 0 (range 0-2). Metastatic sites distribution is as follows: liver (44.1%), lung (13.5%), liver plus lung (12.6%) and other (29.7%). A total of 584 cycles were administered (median 6 cycles/patient, range 2-10). Median follow-up time was 14.5 months (range 1-41 months). In an intent-to-treat analysis, objective responses and stable disease were recorded in 41 (40.4%) and 29 (26.6%) patients, respectively. The median response duration was 5.9 months (range 0.5-28.8). The median progression free-survival (PFS) was 7.5 months (range 1-26 months). The median overall survival (OS) was 15 months (range 1-64 months). The grade 3 toxicities were: neutropenia (8.1%), diarrhea and neurotoxicity (5.4% respectively). Most adverse events were mild to moderate; the most common was acute sensory neuropathy (57.6%). CONCLUSION XELOX is a highly effective first-line treatment for mCRC elderly patients. Response rates, PFS and OS are similar to those observed with fluorouracil/leucovorin/oxaliplatin combinations. XELOX is a convenient regimen, likely to be preferred by both patient and healthcare providers.

Bevacizumab plus irinotecan-, fluorouracil-, and leucovorin-based chemotherapy with concomitant HAART in an HIV-positive patient with metastatic colorectal cancer.

Background: In the era of highly active antiretroviral therapy (HAART), malignancies are the primary cause of increased mortality in patients with human immunodeficiency virus (HIV) infection, hence representing a new challenge for oncologists. To date, there is little evidence in the English literature about chemotherapy treatment in HIV-positive patients with metastatic colorectal cancer. Case Report: We describe the case of an HIV-positive 48-year-old male patient with metastatic colorectal cancer, treated with a bevacizumab, irinotecan, fluorouracil, and leucovorin regimen, with concomitant HAART. No opportunistic infections and grade 3–4 haematological and non-haematological toxicity were reported. The HIV infection was kept under control during the bevacizumab chemotherapy treatment. Conclusions: This case suggests that, in the HAART era, the best multidisciplinary approaches can be offered to HIV-positive patients with metastatic colorectal cancer, who have a good performance status and a well controlled HIV infection. An HIV infection should not preclude the use of the best available chemotherapy treatment in this particular group of patients, including targeted/biological drugs.

Use of Complementary and Alternative Medicine (CAM) in cancer patients: An Italian multicenter survey

Introduction Complementary and Alternative Medicine (CAM) include a wide range of products (herbs, vitamins, minerals, and probiotics) and medical practices, developed outside of the mainstream Western medicine. Patients with cancer are more likely to resort to CAM first or then in their disease history; the potential side effects as well as the costs of such practices are largely underestimated. Patients and method We conducted a descriptive survey in five Italian hospitals involving 468 patients with different malignancies. The survey consisted of a forty-two question questionnaire, patients were eligible if they were Italian-speaking and receiving an anticancer treatment at the time of the survey or had received an anticancer treatment no more than three years before participating in the survey. RESULTS Of our patients, 48.9% said they use or have recently used CAM. The univariate analysis showed that female gender, high education, receiving treatment in a highly specialized institute and receiving chemotherapy are associated with CAM use; at the multivariate analysis high education (Odds Ratio, (OR): 1.96 95% Confidence Interval, CI, 1.27-3.05) and receiving treatment in a specialized cancer center (OR: 2.75 95% CI, 1.53-4.94) were confirmed as risk factors for CAM use. Conclusion Roughly half of our patients receiving treatment for cancer use CAM. It is necessary that health professional explore the use of CAM with their cancer patients, educate them about potentially beneficial therapies in light of the limited available evidence of effectiveness, and work towards an integrated model of health-care provision.