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Heta Shah, Kinsuk Sarker, Rutvi Patel, Rajat Chaudhary, Dhruvi Pandit, Astha Sanyal, Yash Patel, Shruti Rai, Debojyoti Basu, Saurabh Patel, Divyesh Sharma and Prof. Dr. Dhrubo Jyoti Sen*


Alkylating agents were one of the earliest classes of drugs used to treat cancer, beginning in the 1940’s. The biggest weakness of most cancer cells is that they are very sensitive to DNA damage. Alkylating agents work by reacting with the proteins that bond together to form the very delicate double helix structure of a DNA molecule, adding an alkyl group to some or all of them. This prevents the proteins from linking up as they should, cause breakage of the DNA strands and eventually, the death of the cancer cell. This phenomenon is essentially a mutation that takes away the cancer cell’s ability to multiply. While there are many different classes of alkylating agents, they all work by this same chemical mechanism. Alkylating chemotherapy drugs have this effect on a cancer cell during every phase of its life cycle, making them desirable for use on a wide range of cancers. The most benefit is seen in their use to treat cancers that grow slowly, like solid tumors and leukemia, but they are also used to treat lung cancer, ovarian cancer, breast cancer, lymphomas, sarcomas, myelomas and Hodgkin’s disease. The five major categories of alkylating agents are nitrogen mustards, nitrosoureas, alkyl sulfonates, triazines and ethylenimines. The following gives a more detailed description of the most popular drugs in each category. In all cases, dosage and schedule are determined on an individual basis, considering the patient’s size, overall health and the type of cancer being treated. Mechlorethamine, marketed under the trade name Mustargen®, is given by injection to treat Hodgkin’s disease and non-Hodgkin’s lymphoma and as a palliative therapy for breast and lung cancers and given as a topical treatment for skin lesions of mycosis fungoides (cutaneous T-cell lymphoma). Ifosfamide, sold under the trade name Ifex®, is used to treat both Hodgkin’s and non-Hodgkin’s lymphoma, as well as recurrent testicular cancer and germ cell tumors, sarcomas, lung cancer, bladder cancer, head and neck cancer and cervical cancer. It is administered intravenously. Melphalan is a chemotherapy drug sold under the brand name Alkeran® and is also referred to as L-PAM or phenylalanine mustard. It is used to treat multiple myeloma, ovarian cancer, neuroblastoma, rhabdomyosarcoma and breast cancer. It comes as a 2 milligram pill to be taken daily on an empty stomach. More rarely, it can be administered by injection. Chlorambucil is sold by the trade name Leukeran® and is most widely used to treat chronic lymphocytic leukemia, malignant lymphomas including lymphosarcoma, giant follicular lymphoma and Hodgkin’s disease. It has also been successfully used to treat non-Hodgkin’s lymphoma, breast, ovarian and testicular cancer, Waldenstrom’s macroglobulinemia, thrombocythemia and choriocarcinoma. It comes in coated tablet form. Cyclophosphamide is marketed as Cytoxan® or Neosar® and is used to treat Hodgkin’s and non-Hodgkin’s lymphoma, Burkitt’s lymphoma, chronic lymphocytic leukemia, chronic myelocytic leukemia, acute myelocytic leukemia, acute lymphocytic leukemia, t-cell lymphoma, multiple myeloma, neuroblastoma, retinoblastoma, rhabdomyosarcoma, Ewing’s sarcoma; breast, testicular, endometrial, ovarian and lung cancers. Because of the wide variety of cancers it treats, there is also a wide range of administering options. The most common methods are by intravenous injection or mouth in the form of tablets. Tablets should be taken with food and not tampered with. Less commonly, this drug is also approved to be injected directly into muscle, abdominal lining, or lung lining.

Keywords: Sulfur mustard, Nitrogen mustard, DNA, Cytotoxicity, Mitosis, Aziridine, Crosslinking, Intercalation.

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