Estradiol mustard (developmental code name NSC-112259), also known as chlorphenacyl estradiol diester, as well as estradiol 3,17β-bis(4-(bis(2-chloroethyl)amino)phenyl)acetate, is a synthetic, steroidal estrogen and alkylating antineoplastic agent and a nitrogen mustard-coupled estrogen ester that was never marketed.[1] It is selectively distributed into estrogen receptor (ER)-positive tissues such as ER-expressing tumors like those seen in breast and prostate cancers. For this reason, estradiol mustard and other cytostatic-linked estrogens like estramustine phosphate have reduced toxicity relative to non-linked nitrogen mustard alkylating antineoplastic agents. However, they may stimulate breast tumor growth due to their inherent estrogenic activity and are said to be devoid of major therapeutic efficacy in breast cancer,[3] although estramustine phosphate has been approved for and is used (almost exclusively) in the treatment of prostate cancer.

Estramustine is an antineoplastic agent indicated in the palliative treatment of patients with metastatic and/or progressive carcinoma of the prostate. Estramustine is a combination of estradiol with nitrogen mustard. In vivo, the nitrogen-mustard moiety becomes active and participates in alkylation of DNA or other cellular components. This causes DNA damage in rapidly dividing cancerous cells leading to cell death and ideally, tumor shrinkage. Also, due to the drugs estrogen component, it can bind more selectively to active estrogen receptors. Used for the palliative treatment of patients with metastatic and/or progressive carcinoma of the prostate.

Uramustine (INN) or uracil mustard is a chemotherapy drug which belongs to the class of alkylating agents. It is used in lymphatic malignancies such as non-Hodgkin's lymphoma. Uracil Mustard selectively inhibits the synthesis of deoxyribonucleic acid (DNA). The guanine and cytosine content correlates with the degree of Uracil Mustard-induced cross-linking. At high concentrations of the drug, cellular RNA and protein synthesis are also suppressed. After activation, it binds preferentially to the guanine and cytosine moieties of DNA, leading to cross-linking of DNA, thus inhibiting DNA synthesis and function. The DNA damage leads to apoptosis of the affected cells. Chemically it is a derivative of nitrogen mustard and uracil.

Creatinine is a product of metabolism of creatine phosphate, a molecule that serves as a rapidly mobilizable reserve of a brain and skeletal muscle. Creatinine is excreted by kidneys with little or no reabsorption. Serum creatinine is the most commonly used indicator of renal function.

Atrimustine [bestrabucil, busramustine, KM 2210, kregan], a conjugate of estradiol and chlorambucil, is a DNA antagonist that was developed by Kureha Corporation (Japan). Atrimustine is an antineoplastic drug that was used for the treatment of breast cancer, non-Hodgkin's lymphoma, as well as Graft-versus-host disease. Side effects of atrimustine in clinical trials included vaginal bleeding and gynecomastia. Atrimustine reached preregistration in Japan for the treatment of cancer, however, its development has been discontinued.

Trofosfamide is an orally bioavailable antineoplastic agent. Upon administration, it is predominantly metabolized to the cyclophosphamide analog ifosfamide, which is then metabolized by liver cytochrome P450s to the active isophosphoramide mustard (IPM). IPM alkylates DNA to form DNA-DNA cross-links, which may result in inhibition of DNA, RNA and protein synthesis, and tumor cell apoptosis. Trofosfamide is marketed in Germany by Baxter under tradename Ixoten. It is indicated for the treatment of non-Hodgkin's lymphoma after failure of the standard therapy. The drug was investigated in the clinical trials against soft tissue sarcoma and melanoma.

Defosfamide (Mitarson) was developed as antineoplastic agent. Mitarson and radioactive gold were used in some patients with poor results. The most serious complication resulting from therapy was hemorrhagic cystitis.

Trichlormethine is a nitrogen mustard vesicant that has application in chemical warfare and has been used as a cytostatic alkylating agent in leukemia and lymphoma therapy. Trichlormethine was tested for carcinogenicity by subcutaneous injection in mice and rats. The study in mice was inadequate for evaluation. In rats, trichlormethine induced a high incidence of sarcomas (mostly spindle-cell type) in animals of each sex at the site of subcutaneous injection, as well as a few intestinal adenocarcinomas; neither tumor type was seen in controls. Trichlormethine caused vomiting, anorexia and blood-containing feces in dogs a few hours after a single intravenous injection of 1 mg/kg BW. Decreased peripheral lymphocyte counts were observed in rabbits injected intravenously and in mice injected subcutaneously with trichlormethine. Trichlormethine was tested for carcinogenicity by subcutaneous injection in mice and rats. ln rats, trichlormethine induced a high incidence of sarcomas (mostly spindle-cell type) in animals of each sex at the site of subcutaneous injection, as well as a few intestinal adenocarcinomas; neither tumor type was seen in controls. Trichlormethine is possibly carcinogenic to humans (Group 2B).