maytansine and Hyperplasia

Trastuzumab is a monoclonal antibody targeted against the Human Epidermal Growth Factor Receptor 2 (HER2) overexpressed in some breast cancer. This targeted therapy significantly improves the prognosis of these cancers. Recently an anti-HER2 antibodydrug conjugate was shaped in order to facilitate the targeted delivery of potent cytotoxic drug to cancer cells and to reduce resistance. This formulation, called trastuzumab emtansine (T-DM1), consists of the monoclonal antibody trastuzumab linked to a cytotoxic drug (a derivative of maytansine) via a chemical linker. Little is known about adverse reactions due to this new formulation. Herein we described the case of a woman suffering from a HER2-positive breast cancer, treated with trastuzumab for 30 months followed by T-DM1 monotherapy. After 12 months of T-DM1 treatment, a nodular regenerative hyperplasia confirmed by liver biopsy occurred. T-DM1 was stopped and medical imagery showed a resolution of the nodular regenerative hyperplasia. Unfortunately, hepatic metastasis progressed. Few cases of nodular regenerative hyperplasia induced by T-DM1 have been described so far. Further studies are needed to explore pathogenesis of nodular regenerative hyperplasia with this new antibody-drug conjugate treatment.

Topics: Ado-Trastuzumab Emtansine; Biopsy, Needle; Breast Neoplasms; Carcinoma, Ductal, Breast; Female; Follow-Up Studies; Humans; Hyperplasia; Immunohistochemistry; Liver Neoplasms; Magnetic Resonance Imaging; Maytansine; Middle Aged; Molecular Targeted Therapy; Receptor, ErbB-2; Risk Assessment; Trastuzumab; Withholding Treatment

Topics: Ado-Trastuzumab Emtansine; Aged; Antibodies, Monoclonal, Humanized; Breast Neoplasms; Carcinoma, Ductal, Breast; Female; Humans; Hyperplasia; Hypertension, Portal; Liver; Maytansine; Middle Aged; Trastuzumab

Male Wistar Lewis rats were injected with maytansine at a total dose of 0.425 to 0.6 mg/kg over a 3-week period. Biopsies taken at 5 weeks showed that 23% of the bladders had hyperplasia or other abnormalities. Of the bladder biopsies done for the first time at 8 weeks, 80% demonstrated papillary hyperplasia. A small number of biopsies at 13 and 19 weeks still showed hyperplasia and minimal inflammatory reaction. These results were seen regardless of prior biopsy, the presence of bladder calculi, and/or the dose level used. It is not clear from the data whether the observed changes are reversible or precarcinogenic. However, these changes closely resembled the histologic features described in the evolution of bladder cancer in rats fed N-C4-(5-nitro-2-furyl)-2-thiazolyl formamide.

Topics: Animals; Epithelium; Hyperplasia; Male; Maytansine; Oxazines; Rats; Urinary Bladder