Efficacy in high burden locally advanced cervical cancer with concurrent gemcitabine and cisplatin chemoradiotherapy plus adjuvant gemcitabine and cisplatin: prognostic and predictive factors and the impact of disease stage on outcomes from a prospective randomized phase III trial.

OBJECTIVE: We recently published results of a phase III trial demonstrating superior outcomes in patients with locally advanced cervical cancer (LACC) when concurrent cisplatin chemoradiotherapy is supplemented with concurrent gemcitabine and adjuvant gemcitabine/cisplatin. We present prognostic and predictive factors identified in that study, along with analyses of the effect of disease stage and post-study therapy. PATIENTS AND METHODS: In that trial, 515 patients with stage IIB-IVA LACC were administered concurrent cisplatin chemoradiotherapy with or without gemcitabine and adjuvant gemcitabine/cisplatin. Cox models were used to identify prognostic and predictive factors. Survival was estimated using the Kaplan-Meier method. RESULTS: Advanced (stage III-IVA) disease, squamous histology, low hemoglobin, the presence of ≥1 enlarged para-aortic lymph nodes, and large tumor size, were associated with poorer prognosis, regardless of treatment assigned. Tumor size and histology were predictive of treatment efficacy. Chemoradiotherapy supplemented with gemcitabine produced relatively greater benefit in patients with stage III/IVA disease. Post-study therapy did not appear to affect the overall survival outcome. CONCLUSION: Prognostic factors identified in this study are consistent with other reports. The finding of relatively greater benefit in advanced-stage patients makes for an important factor in consideration of treatment for these patients and the design of future studies.

Release of sIL-2R alpha from and activation of native human peripheral blood mononuclear cells by recombinant IL-15.

The cytokine interleukin (IL)-15 shares several activities with IL-2. Both cytokines induced expression of cell-surface IL-2R alpha (CD25) on freshly isolated human peripheral blood mononuclear cells (PBMC) in the absence of other exogenous stimuli. They also stimulated the release of soluble IL-2R alpha and induced proliferation of these cells in 1-week cultures in a time- and dose-dependent manner. Recombinant IL-7 could also induce the expression of CD25, although sIL-2R alpha was released at only low levels. In monocyte-depleted PBMC the sIL-2R alpha release was minimal. When isolated T cells or non-T cells were stimulated by rIL-15 or rIL-2, cell surface CD25 was expressed, but released sIL-2R alpha was undetectable. On stimulation with rIL-15, more than 80% of all natural killer cells expressed CD25 and more CD8br+ lymphocytes were positive for CD25 compared to stimulation by rIL-2. These results may be clinically relevant because several diseases are associated with high serum levels of sIL-2R alpha which may he not only due to IL-2 but also due to IL-15 stimulation.