Background:Hepatitis B virus (HBV) reactivation may occur with chemotherapy and has significant morbidity and mortality. The United States Centre for Disease Control and Prevention recommends pre-chemotherapy hepatitis B screening for all cancer patients, while the American Society of Clinical Oncology finds that there is insufficient evidence currently to support such a recommendation. Apart from anthracyclines, HBV reactivation rates from other commonly used chemotherapy regimens in solid tumours are not well described.Methods:We compared HBV reactivation risk in patients receiving several commonly used chemotherapy regimens for solid tumours associated with different immunosuppression risk at a tertiary cancer centre in an HBV endemic region.Results:A total of 1149 patients were identified, including 434, 196, 245 and 274, respectively, who received doxorubicin-based, oxaliplatin- or irinotecan-based, carboplatin/gemcitabine, and capecitabine chemotherapy. HBV screening rate was 39% overall. Thirty out of 448 (7%) screened patients were HBsAg positive and 28 out of 30 received prophylactic antiviral therapy with no reactivation. Three out of 1149 patients overall (0.3%) developed HBV reactivation, all from the unscreened doxorubicin group (3 out of 214, 1.4%). No unscreened patients (0 out of 487) in the other three treatment groups developed reactivation (P<0.001).Conclusion:Not all chemotherapy regimens result in HBV reactivation. Routine hepatitis B screening for low- or moderate-risk regimens may not be warranted.
770 Background: PK guided dose management and systemic plasma levels of 5FU have shown correlation with both reduced toxicity and improved efficacy. However, data for Asian patients are lacking. Levels are highly variable with doses based on body surface area. Methods: Area under the curve (AUC) was estimated using a nanoparticle immunoassay from Saladax Biomedical (My5-FU). Patients with GI cancers receiving de Gramont, FOLFIRI or mFOLFOX6 regimens had 5 PK sampling time points obtained (reduced to 2 samplings after first 15 patients). If target AUC (18-28 mg.h/L) was reached for 2 consecutive cycles, monitoring is performed for alternate cycles. With dose adjustments, PK sampling will be done in the next cycle. Results: 50 patients (33 males, 17 females) enrolled, with 349 PK samplings done, and 291 analyzable. 31 (62%) had mFOLFOX6, 18 (36%) FOLIRI and 1 (2%) de Gramont. Colorectal cancer (76%) and gastric cancer (12%) were the most common cancer types. Median AUC (35 evaluable) was 24.2 in C1, 23.65 in C2 (n=38), 20.6 in C3 (n=38) and 22 mg.hr/L in C4 (n=35). Proportion of patients achieving target AUC were 54.3%, 32%, 39.5% and 51% respectively and did not change significantly despite PK guided doses adjustments (C1 vs. C4 p=0.81, C2 vs. C3 p= 0.63, C2 vs. C4 p=0.085, C3 vs. C4 p=0.31). Higher than expected rate of G3/4 neutropenia (52%) and fewer mucositis (0%) and diarrhea (8%) were observed. Other toxicities (all grades) were fairly consistent with historical data. There were no inter-cycle differences in rates of toxicity, and no relationship with G3/4 toxicities and high AUC levels were observed. Correlation of response rates, efficacy with AUC were omitted due to heterogeneous tumor types. Conclusions: Contrary to past studies, PK guided 5FU did not result in a greater number of patients achieving target AUC in Asian patients. Furthermore, AUC levels of 5FU did not correlate with toxicity. Larger numbers are needed to confirm the clinical utility and benefit of PK guided 5FU in Asian patients. Clinical trial information: NCT00943137.
A 74-year-old woman had carcinoma of her right breast for which surgery was performed. Four weeks following the start of tamoxifen therapy, she developed papules and plaques over her face, trunk and limbs. A skin biopsy showed perivascular and periadnexal mixed inflammatory cellular infiltrate with fibroplasia. Notably, the dermis also showed squamous epithelial islands, which in foci were noted to be closely associated with eccrine epithelium. This was confirmed with double peroxidase - alkaline phosphatase immunohistochemistry - the eccrine lumina highlighted with carcinoembryonic antigen (polyclonal) and the squamous metaplasia positive for cytokeratin 5/6. Eccrine squamous syringometaplasia was diagnosed. With close clinicopathological correlation, the cutaneous eruption was attributed to tamoxifen. Following discontinuation of the drug, the eruption resolved. Eccrine squamous syringometaplasia has been reported to occur in association with diverse conditions, including skin ulcers, burns and as a cutaneous adverse drug reaction, most commonly to chemotherapeutic drugs. This is believed to be the first report involving tamoxifen.
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