Objective: Previously, we suggested that oxaliplatin (L-OHP)-related grade 3/4 hypersensitivity reactions occurred immediately after the initiation, but grade 1/2 reactions did not. This study was conducted to clarify the risk factors for L-OHP-related hypersensitivity reactions.Methods: Clinical data from 108 Japanese patients with colorectal cancer were analyzed, who were treated with L-OHP-containing regimens, FOLFOX4 and/or mFOLFOX6. The risk factors examined included demographic data, preexisting allergies, laboratory test data, treatment regimen, treatment line of therapy, pretreatment with steroids, total number of cycles and cumulative amount of L-OHP.Results: The incidence of grade 1/2 and grade 3/4 hypersensitivity reactions were found at 13.0% (14/108) and 9.3% (10/108), respectively. Female (P=0.037), preexisting allergies (P=0.004) and lower level of lactate dehydrogenase (P=0.003) were risk factors for grade 1/2 hypersensitivity reactions, and higher neutrophil count (P=0.043) and lower monocyte count (P=0.007) were for grade 3/4 reactions. Total number of cycles were larger in the patients with grade 3/4 reactions than those without reactions (P=0.049).Conclusions: Further extensive examination with a large number of patients is needed to establish a patient management strategy.

Ointments of the skin depigmentation agent hydroquinone (HQ) have been prepared by extemporaneous nonsterile compounding in our hospital. The HQ ointments were highly effective in the treatment of various types of skin pigmentations; however, various problems have emerged including chromatic aberration of the ointments, a relatively large variability of efficacy, and mild topical side effects including irritation. In this paper, the cytotoxicity of HQ was assessed in vitro using rat skin fibroblasts as the concentration with 50% survival after 24 h exposure to be 16.5 microM. The intradermal concentrations at 2 h after application of the HQ ointments was also estimated to be 358 mM and 51.7 mM in stratum corneum and viable tissue (viable epidermis+dermis), respectively, by an in vitro rat skin permeation study with rat full-thickness abdominal skin and Franz-type diffusion cells. It was demonstrated that the intradermal concentration of HQ was much higher than that eliciting cytotoxicity, suggesting that the topical side effects after application of HQ ointment were due to the cytotoxicity of HQ.

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Objective: Clinical laboratory test data obtained prior to treatments were previously analyzed from the standpoint of susceptibility to hypersensitivity reactions in patients treated with the platimun anticancer agent, oxaliplatin (L-OHP). In the present study, the time course from the first to last cycle of the treatment was additionally analyzed to determine a better predictor of these reactions.Methods: A total of 20 laboratory test data were obtained from 108 Japanese patients with advanced colorectal cancer who were treated with the L-OHP-containing regimens, FOLFOX4 and/or mFOLFOX6. The averages and variation coefficients (CV%) of the data until the last cycle of the treatment were compared between patients with hypersensitivity reactions and those without.Results: The average serum lactate dehydrogenase (LDH) level was lower in patients with grade 1/2 reactions (P=0.016), whereas its CV% value was higher in patients with grade 3/4 reactions (P=0.005) than in those without reactions. An increase in serum LDH levels was observed in some patients with grade 3/4 reactions as the cycle number increased, and thereafter hypersensitivity reactions occurred. This phenomenon was not always observed, but was never detected in patients with grade 1/2 reactions.Conclusions: Serum LDH levels may be a predictive marker of hypersensitivity reactions in patients treated with L-OHP. Further extensive examinations with a larger number of patients are needed to establish a patient management strategy.

Ointments of the skin depigmentation agent hydroquinone (HQ) have been prepared by extemporaneous nonsterile compounding in Japan by imitating skin lightening creams commercially available in the U.S.A. and European Union. [1][2][3][4][5][6][7][8] In our hospital, HQ ointments consisting of 5 or 10% HQ, 1.6% L(ϩ)-ascorbic acid (AsA), 0.5% Na 2 SO 3 , 10% (v/w) glycerin and hydrophilic ointment have been prepared (Table 1). 9) However, various problems have been observed during usage for about 4 years including chromatic aberration of the ointments, a relatively large variability of efficacy, and mild side effects. In our previous report, the pharmaceutical and clinical properties of HQ ointments were evaluated, and the following observations were made: 1) HQ ointments were highly effective in the treatment of various types of skin pigmentations; 2) Chromatic aberration occurred during 3 months of storage; 3) Chromatic aberration was independent of the prescribed HQ content; 4) Removal of both antioxidants resulted in the suppression of chromatic aberration; 5) Removal of Na 2 SO 3 only was further effective in suppressing chromatic aberration; 6) Chromatic aberration was due to a newly developed water-soluble material and insoluble noncovalent complex formed by HQ and p-benzoquinone, which was formed from HQ.In this paper, the effects of various storage conditions on the chromatic aberration and HQ content of HQ ointments for clinical use were evaluated to clarify the conditions that encourage or discourage the chromatic aberration. The storage conditions were chosen to imitate the actual situation during usage by patients. In addition, various types of HQ ointments were also prepared to find a formulation to minimize chromatic aberration. A relationship between the acidity of ointments and chromatic aberration was also demon-strated by addition of HCl or NaOH to the ointments.

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