Prostate-specific antigen growth rate constant after first-line cytotoxic chemotherapy in metastatic castration-resistant prostate cancer: a monoinstitutional experience.

OBJECTIVE: Validation in clinical practice, after first-line chemotherapy (CT) of metastatic castration-resistant prostate cancer (PC), of prostate-specific antigen growth rate constant logarithm (PSA-G), calculated by a formula developed by Stein et al. in comparison with PSA decrease (PSA-D), calculated as recommended by PCWG2. PATIENTS AND METHODS: This study is a retrospective monoinstitutional assessment of PSA-G and PSA-D after 12 weeks from the beginning of first-line cytotoxic CT in 49 patients with metastatic castration-resistant PC treated from 2006 to 2011, and whose pre-CT PSA and post-CT PSA determinations have been measured at specific time points. The 12-week PSA was measured at 80 to 91 days from the beginning of CT. RESULTS: PSA-G exhibited a significant correlation with overall survival by Mann-Whitney U test and by linear regression, whereas PSA-D did only at the first test. After multivariate analysis, PSA-G was the only posttreatment measure to predict overall survival. CONCLUSION: PSA-G appears a reliable surrogate end point after first-line cytotoxic CT outside of clinical trials. A cutoff value of PSA-G post-CT higher than-2.4 could be considered suggestive for moving to another treatment.

CA125-related measures of tumor kinetics and outcome of patients with recurrent ovarian cancer receiving chemotherapy: a retrospective evaluation.

OBJECTIVE: Defining 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. METHODS: A 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. RESULTS: Among 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. CONCLUSIONS: The 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.

Uveal melanoma.

Uveal melanoma, which arises from melanocytes residing in the stroma, is the most common primary intraocular tumor in adults. Up to 50% of patients with primary uveal melanoma will ultimately develop distant metastasis, the liver being involved in up to 90% of individuals and the median survival reported to be 4-5 months. The current treatment of metastatic uveal melanoma is limited by the lack of effective systemic therapy. The intrinsic resistance of uveal melanoma to conventional systemic chemotherapy has led researchers to evaluate new approaches. Molecular biology and a better knowledge of cancer cells allowed the development of target therapies: these refer to drugs designed to interact with a specific molecular pathway known to have a critical role in tumor growth or progression. Several drugs, such as bevacizumab, imatinib and MEK-inhibitors, are currently under investigation as single agents or in combination with chemotherapeutic drugs for the treatment of metastatic uveal melanoma. Finally, ipilimumab, which targets the immune compartment, was reported to increase overall survival in cutaneous melanoma patients, with preliminary evidence of similar activity in ocular melanoma.

Impaired response to influenza vaccine associated with persistent memory B cell depletion in non-Hodgkin's lymphoma patients treated with rituximab-containing regimens.

Influenza vaccination is generally recommended for non-Hodgkin's lymphoma (NHL) patients, but no data are available about the activity of this vaccine after treatment with rituximab-containing regimens. We evaluated the humoral response to the trivalent seasonal influenza vaccine in a group of NHL patients in complete remission for ≥6 mo (median, 29 mo) after treatment with rituximab-containing regimens (n = 31) compared with age-matched healthy subjects (n = 34). B cell populations and incidence of influenza-like illness were also evaluated. For each viral strain, the response was significantly lower in patients compared with controls and was particularly poor in patients treated with fludarabine-based regimens. In the patient group, the response to vaccination did not fulfill the immunogenic criteria based on the European Committee for Medicinal Products for Human Use requirements. Among the patients, CD27(+) memory B cells were significantly reduced, and their reduction correlated with serum IgM levels and vaccine response. Episodes of influenza-like illness were recorded only in patients. These results showed that NHL patients treated with rituximab-containing regimens have persisting perturbations of B cell compartments and Ig synthesis and may be at particular risk for infection, even in long-standing complete remission.