If it is determined that a tumor is overexpressing the erbB2 oncogene and the patient has no significant pre-existing heart disease, then a patient is eligible for treatment with trastuzumab. It is surprising that although trastuzumab has great affinity for HER2 and high doses can be administered (because of its low toxicity), 70% of HER2+ patients do not respond to treatment. In fact resistance to the treatment develops rapidly, in virtually all patients. A mechanism of resistance involves failure to downregulate p27 (Kip1)   as well as suppressing p27 translocation to the nucleus in breast cancer, enabling cdk2 to induce cell proliferation.In May 2021, the FDA approved pembrolizumab in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of people with locally advanced unresectable or metastatic HER2 positive gastric or gastroesophageal junction (GEJ) adenocarcinoma. Duration of treatment
The optimal duration of add-on trastuzumab treatment after surgery for early breast cancer is unknown. One year of treatment is generally accepted based on clinical trial evidence that demonstrated the superiority of one-year treatment over none. However, a small Finnish trial also showed similar improvement with nine weeks of treatment over no therapy. Because of the lack of direct head-to-head comparison in clinical trials, it is unknown whether a shorter duration of treatment may be just as effective (with fewer side effects) than the accepted practice of treatment for one year. Debate about treatment duration has become a relevant issue for many public health policy makers because administering trastuzumab for a year is very expensive.
Demeclocycline (INN, BAN, USAN, brand name Declomycin) is a tetracycline antibiotic which was derived from a mutant strain of Streptomyces aureofaciens. Uses
Demeclocycline is officially indicated for the treatment of various types of bacterial infections. It is used as an antibiotic in the treatment of Lyme disease, acne, and bronchitis. Resistance, though, is gradually becoming more common, and demeclocycline is now rarely used for treatment of infections.It is widely used (though off-label in many countries including the United States) in the treatment of hyponatremia (low blood sodium concentration) due to the syndrome of inappropriate antidiuretic hormone (SIADH) when fluid restriction alone has been ineffective. Physiologically, this works by reducing the responsiveness of the collecting tubule cells to ADH.The use in SIADH actually relies on a side effect; demeclocycline induces nephrogenic diabetes insipidus (dehydration due to the inability to concentrate urine).The use of demeclocycline in SIADH was first reported in 1975, and, in 1978, a larger study found it to be more effective and better tolerated than lithium carbonate, the only available treatment at the time. Demeclocycline used to be the drug of choice for treating SIADH. Meanwhile it might be superseded, now that vasopressin receptor antagonists, such as tolvaptan, became available. Contraindications
Like other tetracyclines, demeclocycline is contraindicated in children and pregnant or nursing women. All members of this class interfere with bone development and may discolour teeth. Side effects and interactions
These are similar to those of other tetracyclines. Skin reactions with sunlight have been reported.