Procalcitonin and C-Reactive Protein/Procalcitonin Ratio as Markers of Infection in Patients With Solid Tumors.

Objectives: The roles of procalcitonin (PCT) and C-reactive protein (CRP) in febrile cancer patients is currently unclear. Our aim was to assess these in febrile patients with solid tumors and to identify cut-off values for ruling out infection. Methods: We retrospectively evaluated patients with solid tumors admitted to hospital due to fever. They were divided into those with Fever with microbiologically documented infection (FMDI), Fever with clinically documented infection (FCDI) and Tumor-related fever (TRF). PCT and CRP levels were compared. Receiver-operating curves were plotted to define the best cut-off values for discriminating between infection-related and cancer-related fever. Results: Between January 2015 to November 2018, 131 patients were recorded (mean age 68 years, 67% male, 86% with metastasis). Patients with FMDI or FCDI had significantly higher baseline levels of PCT and lower CRP/PCT than those with TRF. A PCT cut-off value of 0.52 ng/mL for discriminating between infection and cancer-associated fever yielded 75% sensitivity, 55% specificity, 77% positive predictive value (PPV), and 52% negative predictive value (NPV). A CRP/PCT ratio with a cut-off value of 95 showed 56% sensitivity, 70% specificity, 79% NPV, and 44% PPV. Discussion: PCT is a sensitive marker of sepsis or localized infection in patients with solid tumors, but its specificity is poor. The CRP/PCT ratio improves specificity, thus providing a reliable means of ruling out infection for values above 95.

Cetuximab is efficient and safe in patients with advanced cutaneous squamous cell carcinoma: a retrospective, multicentre study.

There is no standard of care for unresectable cutaneous squamous cell carcinoma (cSCC). Chemotherapy, alone or combined with radiotherapy, is commonly used mostly as palliative treatment; moreover, its poor safety profile limits its use most of the time, especially in elderly patients. Thus, alternative options are needed. Targeted molecular inhibitors, such as the epidermal growth factor receptor inhibitor cetuximab, seem promising, but data are limited. We retrospectively evaluated clinical outcomes of cetuximab as a single agent in this indication. The primary endpoint was the Disease Control Rate (DCR) at 6 weeks according to RECIST criteria. Secondary endpoints included DCR at 12 weeks, objective response rate (ORR) at 6 and 12 weeks, progression-free-survival (PFS), overall survival (OS), and safety profile. Fifty-eight patients received cetuximab as monotherapy. The median age was 83.2 (range, 47.4 to 96.1). The majority of patients was chemotherapy naïve. The median follow-up was 11.7 months (95% CI: 9.6-30.1). The DCR at 6 and 12 weeks was 87% and 70%, respectively. The ORR was 53% and 42%, respectively, at 6 and 12 weeks. The median PFS and OS were 9.7 months (95% CI: 4.8-43.4) and 17.5 months (95% CI: 9.4-43.1), respectively. Fifty-one patients (88%) experienced toxicity, and 67 adverse events related to cetuximab occurred. Most of them (84%) were grade 1 to 2. Our study shows that cetuximab is safe and efficient for the treatment of patients, even elderly ones, with advanced cSCC. These results indicate that cetuximab is a promising agent to test in new combinations, especially with immune checkpoint inhibitors such as anti-PD-1 agents.

Short-course daptomycin lock and systemic therapy for catheter-related bloodstream infections: a retrospective cohort study in cancer patients with surgically implanted devices.

PURPOSE: Few in vivo studies have been reported describing efficacy and duration of antibiotic lock therapy (ALT) with daptomycin (DPT) for long-term catheter-related bloodstream infections (CRBSI) due to coagulase-negative staphylococci (CoNS). We retrospectively analysed the efficacy of short-course ALT with DPT in combination with systemic treatment (ST) for CoNS-associated CRBSI in our hospital. METHODS: Patients admitted for CoNS-associated CRBSI and treated with DPT as ALT and ST were retrospectively analysed. Success was defined as preservation of the catheter device 30 days after ending treatment. Catheter removal within 30 days of discontinuing treatment, for either microbiological documentation of CRBSI relapse or re-occurrence of unexplained fever, was considered as failure. RESULTS: Among 7610 patients admitted to the Departments of Internal Medicine/Infectious Diseases and Pneumology in Cannes from January 2013 to November 2015, we identified 28 episodes of CoNS-associated CRBSI. Seven patients died of cancer during follow-up. Thus, 21 episodes were analysed among 20 patients (median age 67 years, 12 males, all treated for neoplasia and carrying a port-a-cath® device). Staphylococcus epidermidis was the main agent responsible for CRBSI. Median duration of systemic and ALT DPT was 3 days, in combination with rifampin for 4 days and then generally followed by a switch to oral drugs, most frequently cotrimoxazole or linezolid, to achieve 14 median days of treatment. Clinical success and failure rates were 76% and 24%, respectively. CONCLUSIONS: Short-course DPT as ALT, combined with 14 days of ST, allowed conservative management of CoNS-associated CRBSI in surgically implanted-catheters in three-fourth of cases.

Visceral leishmaniasis due to Leishmania infantum with renal involvement in HIV-infected patients.

BACKGROUND: We describe histological, clinical findings and outcomes of renal involvement during Leishmania infantum infection in four HIV-infected patients in South France and North Italy hospital settings. CASES PRESENTATION: Four HIV-infected Caucasian patients (age 24-49) performed renal biopsy during episodes of visceral leishmaniasis. They presented severe immunosuppression, frequent relapses of visceral leishmaniasis during a follow-up period of several years and partial or complete recovery of renal function after anti-parasitic treatment. Main clinical presentations were nephrotic or nephritic syndrome and/or acute renal failure secondary to membranoproliferative type III glomerulonephritis or acute interstitial nephritis. Clinical outcome was poor, probably as a consequence of insufficient immuno-virological control of the HIV infection. CONCLUSIONS: Our findings suggest that the main histological findings in case of renal involvement due to Leishmania infantum infection in HIV-infected patients are type III MPGN and acute interstitial nephritis, with a histological specificity similar to that observed in canine leishmaniasis. Poor immune status in HIV-infected patients, altering the capacity for parasite clearance, and prolonged course of chronic active VL in this population may lead to the development of specific renal lesions.

Final results of ERASME-4: a randomized trial of first-line docetaxel plus either capecitabine or epirubicin for metastatic breast cancer.

OBJECTIVE: To assess the efficacy of capecitabine plus docetaxel (XT) versus epirubicin plus docetaxel (ET) as first-line therapy for metastatic breast cancer (MBC). PATIENTS AND METHODS: Patients with no prior chemotherapy for MBC were randomized to 3-weekly cycles of either XT (capecitabine 1,000 mg/m(2) twice daily, days 1-14; docetaxel 75 mg/m(2), day 1) or ET (epirubicin 75 mg/m(2), day 1; docetaxel 75 mg/m(2), day 1). The primary endpoint was non-progression rate 6 months after randomization. The planned sample size was 106 patients based on a randomized, phase II selection design. RESULTS: Between April 2004 and January 2007, 68 patients were randomized, giving 82% power to select the best regimen according to a 6-month non-progression rate. Slow accrual led to premature study termination. Baseline characteristics were generally well balanced between arms. The 6-month non-progression rates were 75.8% with XT versus 65.7% with ET (p = 0.36). After 42 months' median follow-up, median progression-free survival was 12.4 versus 6.8 months, respectively (p = 0.040). The safety profiles were consistent with previous experience. CONCLUSION: Further larger studies are warranted to validate these results. Despite more grade 3 hand-foot syndrome, first-line XT may be a valid alternative to ET, potentially improving efficacy.

Phase II trial evaluating a docetaxel-capecitabine combination as treatment for hormone-refractory prostate cancer.

BACKGROUND: Docetaxel is a well-recognized drug in patients with hormone-refractory prostate cancer (HRPC), either alone or combined with estramustine. In this indication, a Phase II trial was conducted investigating a docetaxel-capecitabine combination. METHODS: Forty-six patients presenting with documented HRPC were enrolled in the study. The treatment regimen consisted of docetaxel (D) at a dose of 35 mg /m2/week (intravenously, 3 consecutive weeks) plus oral capecitabine (C) at a dose of 625 mg/m2 twice daily (Days 5-18) every 28 days for 4 cycles. The primary endpoint was the biological response defined as a reduction in prostate-specific antigen (PSA) level > or =50%. Secondary endpoints were overall survival, safety, and quality of life. RESULTS: Thirty of 44 assessable patients (68.2%) achieved a biological response, 14 of whom (31.8%) normalized their PSA value. The median overall survival time was 17.7 months (95% confidence interval, 15.8 to not reached). Four treatment cycles were completed by 87% of the patients. Hematologic toxicity was mild. The main Grade 3-4 toxicities were cutaneous toxicity (13.1%) and changes in nails (6.5%). Physical functioning and role scales were higher before treatment (P = .02 and P = .003, respectively), fatigue and diarrhea were more frequent during and after treatment (P = .0003 and P = .03, respectively), and pain was lower during and after treatment. CONCLUSIONS: The results of the current study demonstrated the high efficacy of the DC combination in patients with HRPC, and the associated good tolerability. This combination offers a new alternative to the docetaxel-estramustine combination. Further randomized trials are warranted.

Incidence of non-AIDS-defining cancers before and during the highly active antiretroviral therapy era in a cohort of human immunodeficiency virus-infected patients.

PURPOSE: To determine incidence of non-AIDS-defining cancers (NADC) in HIV-infected patients before (P1) and during (P2) the use of highly active antiretroviral therapy (HAART) relative to that observed in the French general population (FGP) of the same age and sex. PATIENTS AND METHODS: Sex- and age-adjusted NADC standardized incidence ratios (SIR), with FGP as reference, were estimated in 1992 to 1995 (P1) and in 1996 to 1999 (P2) in a French Hospital Database on HIV prospective hospital cohort study. RESULTS: NADCs were diagnosed in 260 patients during P1 and 391 patients during P2 among the 77,025 patients included in the database between January 1, 1992, and December 31, 1999. Estimated incidence of all cancers was higher in HIV-infected men than in FGP during both periods (P1 SIR = 2.36 and P2 SIR = 1.91). No excess of cancers was observed among HIV-infected women in either period. Incidence of all cancers did not change from P1 to P2 in either sex (SIR = 0.96 for men and 1.00 for women). In contrast, incidence of Hodgkin's disease (HD) was higher than in FGP in both sexes and both periods and increased in P2 as compared with P1; incidence of lung cancer was higher in both sexes during P2. CONCLUSION: Relative to FGP, the overall incidence of NADCs was increased in HIV-infected men but not in women and did not differ between P1 and P2. Only HD was much more common in HIV infection, and the potential role of HAART on HD cannot be excluded.