Purpose To identify sunitinib alternative schedules (AS) that maintained dose intensity while decreasing adverse events (AEs) in patients with metastatic renal cell cancer (mRCC), and to determine impact of AS on clinical outcomes. Patients and Methods A retrospective review of patients ≥ 18 yr of age with clear-cell mRCC who received first-line sunitinib between 1/26/06 and 3/1/11 at a major Comprehensive Cancer Center. Subset of patients switched at first intolerable AE from traditional schedule (28 d on, 14 d off; TS) to 14 d on/7 d off schedule or other AS. Control group underwent standard dose reduction. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Predictors of PFS and OS were analyzed using Cox regression. Results One hundred eighty five patients were included for analysis; 87% were on TS at baseline. During treatment, 53% of patients continued TS and 47% initiated or transitioned to AS. Baseline characteristics were similar. AEs prompting schedule modification included fatigue (64%), hand-foot syndrome (38%) and diarrhea (32%). Median time to AS was 5.6 mo. Median OS was 17.7 mo (95% confidence interval [CI], 10.8-22.2) on TS compared to 33.0 mo (95% CI, 29.3- not estimable) on AS (P < 0.0001). By multivariable analysis; poor ECOG PS, increased LDH, decreased albumin, unfavorable Heng criteria, and TS are associated with decreased OS (P < 0.05). Conclusion Sunitinib administered on AS may mitigate AEs and has comparable outcomes as TS for mRCC patients. Prospective investigations of alternate dosing schemas are warranted.

In April 2010, sipuleucel-T became the first anticancer vaccine approved by the United States Food and Drug Administration. Different from the traditional chemotherapy agents that produce widespread cytotoxicity to kill tumor cells, anticancer vaccines and immunotherapies focus on empowering the immune system to overcome the tumor. The immune system consists of innate and adaptive components. The CD4+ and CD8+ T cells are the most crucial components of the adaptive arm of the immune system that act to mediate antitumor responses. However, T-cell responses are regulated by intrinsic and extrinsic mechanisms, which may interfere with effective antitumor responses. Many anticancer immunotherapies use tumor-associated antigens as vaccines in order to stimulate an immune response against tumor cells. Sipuleucel-T is composed of autologous mononuclear cells incubated with a fusion protein consisting of a common prostate cancer antigen (prostatic acid phosphatase) linked to an adjuvant (granulocyte-macrophage colony-stimulating factor). It is postulated that when the vaccine is infused into the patient, the activated antigen-presenting cells displaying the fusion protein will induce an immune response against the tumor antigen. In a recent randomized, double-blind, placebo-controlled, phase III clinical trial, sipuleucel-T significantly improved median overall survival by 4.1 months in men with metastatic castration-resistant prostate cancer compared with placebo. Although overall survival was improved, none of the three phase III clinical trials found a significant difference in time to disease progression. This, along with cost and logistic issues, has led to an active discussion. Although sipuleucel-T was studied in the metastatic setting, its ideal place in therapy is unknown, and clinical trials are being conducted in patients at different stages of disease and in combination with radiation therapy, antiandrogen therapy, and chemotherapy. Various other anticancer vaccines and immunotherapies for other tumor types are currently under investigation and in clinical trials. These immunotherapies were formulated to incorporate tumor-associated antigens aimed at stimulating effector T-cell responses or to block regulatory mechanisms that suppress the function of effector T cells. Additional studies will determine how these therapies can best improve clinical outcomes in patients with cancer.

Candida lusitaniae, a Candida species frequently resistant to amphotericin B (AMB), is a rare cause of candidemia. The clinical significance of this in vitro resistant phenotype, the risk factors for, and the clinical presentation of C. lusitaniae fungemia in comparison with those of Candida albicans have not been completely characterized. We reviewed 13 consecutive cases of C. lusitaniae fungemia in cancer patients and compared them with 41 consecutive cases of C. albicans fungemia (1990-2004). The AMB mutational frequency and rate of fungicidal activity was compared between a bloodstream, AMB-susceptible C. lusitaniae isolate associated with clinical failure and reference C. albicans and Candida glabrata strains. In multivariate analysis, patients having C. lusitaniae fungemia were more likely to have neutropenia (p=0.001), stem cell transplantation (p=0.014) and to have received prior antifungals (p=0.04). Mutational frequencies at clinically-achievable AMB exposures were 8 x 10(5) for C. lusitaniae and <1 x 10(9) for C. albicans and C. glabrata reference strains. Compared to C. albicans and C. glabrata, AMB had much less fungicidal activity against C. lusitaniae in time-kill curve analysis. Clinically, C. lusitaniae fungemia was more frequently associated with stem cell transplant and neutropenia. C. lusitaniae, even originally susceptible to AMB, might be less amenable to AMB therapy.

To determine whether pre-treatment neutrophil/lymphocyte (NLR) or platelet/lymphocyte ratios (PLR) are predictive for progression in early-stage classical Hodgkin lymphoma (cHL), we derived NLR and PLR values for 338 stage I/II cHL patients and appropriate cut-off point values to define progression. Two-year freedom from progression (FFP) for patients with NLR ≥6·4 was 82·2% vs. 95·7% with NLR <6·4 (P < 0·001). Similarly, 2-year FFP was 84·3% for patients with PLR ≥266·2 vs. 96·1% with PLR <266·2 (P = 0·003). On univariate analysis, both NLR and PLR were significantly associated with worse FFP (P = 0·001). On multivariate analysis, PLR remained a significant, independent prognostic factor (P < 0·001).

Based on our preliminary data, we conclude that patients with advanced prostate cancer referred to PC experience severe and clinically significant symptoms. An outpatient PCconsultation is associated with significant symptom improvement in this subset of a distressed population. Future prospective studies are warranted to further describe symptom burden and the role for outpatient PC for advanced prostate cancer patients.

Objectives To identify the clinical outcomes of mRCC patients with PM treated with either pazopanib or sunitinib and assess whether PM is an independent prognostic variable in the current therapeutic environment. Patients and Methods Retrospective review of mRCC patients in an outpatient clinic was done from January 2006 to November 2011. Patient characteristics including demographics, laboratory data, and outcomes were analyzed. Comparison of baseline characteristics was done using chi2 and t-test and Overall Survival (OS) and Cancer-Specific Survival (CSS) was estimated using Kaplan-Meier methods. Predictors of OS were analyzed using Cox regression. Results A total of 228 patients were reviewed of which 44 (19.3%) had metastases to the pancreas and 184 (81.7%) had metastasis to sites other than the pancreas. The distribution of baseline characteristics was equal in both groups with the exception of a higher incidence of prior nephrectomy, diabetes and number of metastatic sites in the pancreatic metastasis group. 4 patients had isolated metastases to the pancreas, however, the majority of patients (68%) with pancreatic metastases had at least three different organ sites of metastases, as compared to 29% in patients without pancreatic metastases (p<0.01). Distribution of organ sites of metastases was similar (p>0.05), excluding pancreas. Median OS was 39 months (95% confidence interval [CI], 24–57, HR=0.66, 95% CI = 0.42–0.94, p=0.02) for patients with pancreatic metastases, compared to 26 months (95% CI, 21–31) for patients without pancreatic metastases (p-value <0.01). CSS was 42 months (95% CI: 30–57 months) in the PM group and 27 months (95% CI: 22–33 months, p-value = 0.05) in the control group. Conclusions Despite a higher number of affected organ sites in the pancreatic metastasis cohort, mRCC behavior in this cohort appears to be more indolent, as demonstrated by a higher median OS. These findings suggest that host or tumor features associated with pancreatic metastases may represent a less aggressive tumor phenotype.

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Renal cell carcinoma (RCC) encompasses a heterogeneous group of histological subtypes of which clear-cell RCC (CCRCC) is the most common comprising more than 70–80% of all cases. Papillary renal cell carcinoma (PRCC) is the next most common comprising 10–15% of cases. PRCC is refractory to chemotherapy, immunotherapy and hormonal therapy. Insights into the biology of clear-cell RCC have identified multiple pathways associated with the pathogenesis and progression of this cancer. This has led to the development of multiple agents targeting these pathways including the small molecule tyrosine kinase inhibitors sorafenib, sunitinib and pazopanib, the monoclonal antibody bevacizumab and the mTOR inhibitors temsirolimus and everolimus. These drugs have shown significant clinical benefits in randomised trials in advanced CCRCC and have become the standard of care for most patients. With the exception of temsirolimus, phase III trials tested these agents in patients with clear-cell histology, and therefore, their efficacy in non-clear cell RCC is unclear. To date, there is no established effective therapy for patients with advanced non-clear cell RCC (NCCRCC). This review will focus on the treatment options of metastatic NCCRCC.