Cyclophosphamide with or without fluorouracil followed by subcutaneous or intravenous interleukin-2 use in solid tumors: A feasibility off-label experience.

BACKGROUND: Immune tolerance seems to correlate with disease progression and T regulatory cells (Tregs) and myeloid-derived suppressor cells play a relevant role in immunosuppression. Cyclophosphamide (Cyt) and Fluorouracil (FU) seem to reduce these cell populations. METHODS AND OBJECTIVE: Establishing safety, feasibility, activity and impact on the immune system (neutrophil/lymphocyte [N/L], platelet/L [Plt/L], monocyte [M] and lymphocyte subpopulation (CD3, CD4, CD8, CD16, HLADR/CD3, Tregs, cells count), CD8/Treg and C-reactive protein (CRP). TREATMENT: 1) Cyt 300 mg/sqm ±â€¯FU 500 mg/sqm day (d) 1 and interleukin 2 (IL-2) 18 MUI/sqm intravenous (I.V.) d 4-6, 18-20 or 2) Cyt 300 mg/sqm + FU 500 mg/sqm day d 1, IL-2 4.5 MUI subcutaneous (S.C.) d 3-6, 17-20. The cycle was repeated every four weeks for 2 cycles. Stable or responding patients (pts) continued therapy for 3 cycles. RESULTS: From February 2014 to December 2016, 13/14 pre-treated pts (mean 3 lines) with solid tumors were enrolled. Male/Female: 1/1. The median age and Eastern Cooperative Oncology Group Performance Status (ECOG PS) was 68 years and 1 respectively. Mean 2 cycles of therapy were administered. G3-4 toxicities presented as diarrhea and bleeding anemia in 2 pts and proteinuria and erhytroderma in 1pt, respectively. Regarding the hematological profile, a more reduction in Plt, less decrease of Plt/Ly, and less increase of Treg with I.V. than S.C. IL-2 administration was observed. However a transient decrease of Treg on day 7 of first cycle in the I.V. IL-2 was reported. RESPONSE: PR 3 (23%), SD 3 (23%), PD 7 (54%). The response duration was 2+ and 3 months in 2 HCC and 18+ months in the pancreatic cancer (PC). Pathological CR was reported in one HCC treated with I.V. IL-2. The median progression-free-survival (PFS) and overall survival (OS) were 1 and 7 months. CONCLUSION: Cyt-FU-IL-2 can be considered safe, feasible and moderately active in heavily pre-treated pts. Plt, Plt/Ly, CD8/Treg and a transient Tregs reduction were observed without significative difference on survival.

Cumulative effects of volcanic ash on the food preferences of two Orthopteran species.

Inert dusts are an early form of insecticide which is still in use. One of the most common inert dusts is volcanic ash. In order to study the reaction of rangeland grasshoppers, Dichroplus vittigerum (Acrididae) and a katydid, Burgilis mendosensis (Phaneropteridae), to the presence of volcanic ash in their food sources and how this reaction changed as a function of time, we conducted paired preference tests between clean leaves of their preferred host plant and leaves exposed to volcanic ash of different grain size. The behavioral response was measured as the rating on the Thurstonian preference scale of leaves with ash in relation to clean leaves. The results showed that the avoidance of volcanic ash increased as a function of time in both species. Both species studied are occasionally exposed to volcanic activity, and come from an area in which a volcanic eruption had recently occurred. As their populations did not decrease after the ash fall, we propose that some behavioral responses such as avoidance of places with ash, works as tolerance mechanism to inert dusts exposure.