Cetuximab-induced skin reactions are suppressed by cigarette smoking in patients with advanced colorectal cancer.

BACKGROUND: Smoking is widely accepted as the most important risk factor for cancer in the modern world. Several constituents of cigarette smoke are known to interact with drug-metabolizing enzymes, potentially affecting the outcomes of drug treatment. Cetuximab (Erbitux(®); Merck Serono) is indicated for the treatment of colorectal cancer with respect to restoring chemosensitivity to irinotecan in irinotecan-resistant patients. The purpose of this study was to determine whether cigarette smoking adversely affects the actions of cetuximab in the treatment of colorectal cancer. METHODS: We studied 56 patients with colorectal cancer who were treated with cetuximab in our hospital during the time period from 2009 through 2010. We compared the adverse reaction rates of 16 patients who smoked (smokers) with those of 38 patients who did not smoke (non-smokers, including 16 patients who never smoked and 22 patients who were former smokers). RESULTS: The incidence of skin reactions after cetuximab treatment was lower in the smokers than in the non-smokers. In addition, the incidence of anorexia was higher in the smokers than in the non-smokers. Within the group of non-smokers, no statistically significant differences were observed between the never smokers and the former smokers with regard to adverse reactions. CONCLUSION: Our findings suggest that cigarette smoking during anticancer treatment with cetuximab-based regimens reduces the skin reaction, which leads to a reduction in the benefit of the treatment; therefore, patients should quit smoking, at least while receiving cetuximab-based treatment.

Quantitation and human monocyte cytotoxicity of the polymerization agent 1-hydroxycyclohexyl phenyl ketone (Irgacure 184) from three brands of aqueous injection solution.

In this study, levels of the photoinitiator 1-hydroxycyclohexyl phenyl ketone (1-HCHPK) in aqueous injection solutions were analyzed by GC-MS. In our previous studies, photoinitiators such as 2-methyl-4'-(methylthio)-2-morpholinopropiophenone (MTMP) were detected in intravenous (i.v.) injection bag solution, and they were found to be cytotoxic to human monocytes. Therefore, we hypothesized that 1-HCHPK might display similarly cytotoxicity. The purpose of this study was to quantitate the amount of contaminants from plastic containers such as those used for peripheral parenteral nutrition and to determine the cytotoxicity of such extracts on human monocytes. The sample extraction procedure for GC-MS analysis involved a liquid-phase extraction. The solvent was evaporated under a stream of nitrogen at 50°C to yield a residue, which was dissolved in n-hexane and injected into a GC-MS. Normal human peripheral blood mononuclear cells (PBMC), isolated from the buffy coat by centrifugation, were suspended in RPMI 1640 medium supplemented with 10% (v/v) heat-inactivated fetal calf serum. In the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assay, cells (1×10(4)) were treated with 1-HCHPK for 24 h or 48 h at 37°C. From the GC-MS analysis, 6.13-8.32 µg/mL of 1-HCHPK was found in 20 mL vials of water for injection solution. In the MTT assay, 1-HCHPK decreased cell viability for both the 24 h and 48 h incubation periods. In conclusion, our findings suggest that 1-HCHPK could promote adverse events in patients. Future studies will clarify the possible health risks of photoinitiator accumulation in human cells.

Cytotoxicity of the polymerization agent, 2-methyl-4'-(methylthio)-2-morpholinopropiophenone on human monocytes.

This is the first study to detect 2-methyl-4'-(methylthio)-2-morpholinopropiophenone (MTMP) from an intravenous injection bag solution by GC-MS. In previous studies, several other photoinitiators were reported to be very cytotoxic. Therefore, we theorized that photoinitiators such as MTMP might also have adverse cellular effects. The purpose of this study was to quantitate the amounts of contaminants from plastic containers such as those used for peripheral parenteral nutrition and to determine the cytotoxicity of such extracts on human monocytes. The sample extraction procedure for GC-MS analysis involved a liquid-phase extraction. The solvent was evaporated under a stream of nitrogen at 50°C. The residue was dissolved in n-hexane and injected into a GC-MS. Normal human peripheral blood mononuclear cells (PBMC), isolated from the buffy coat by centrifugation, were suspended in RPMI 1640 medium supplemented with 10% (v/v) heat-inactivated fetal calf serum. In the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cells (1×10(4)) were treated with MTMP for 24 h or 48 h at 37°C. From the GC-MS analysis, 5.62 ± 1.03 µg/mL of MTMP was found in the BFLUID(®) Injection 500 mL solution. In the MTT assay, MTMP decreased cell viability in a dose-dependent manner for both the 24 h and 48 h incubation periods. Our findings suggest that photoinitiators could promote adverse effects in patients. Future studies will clarify the possible health risks of photoinitiator accumulation in human cells.