Cancer, treatment using antineoplastic Agents

While most drugs do not directly interact with endogenous metals, two clinically used antineoplastic agents are distinguished by this attribute bleomycin and doxorubicin. Metals also have a role in the treatment of cancer. The platinum-based antineoplastic agents, cw-diamminedichloro-platinum(II) (cisplatin) and cw-diamminedicarboxylatocyclobutaneplatinum... 

Cancer or neoplastic disease is a genomic disorder of the body s own cells which start to proliferate and metastasize in an uncontrolled fashion that is ultimately detrimental to the individual. Antineoplastic agents are used in conjunction with surgery and radiotherapy to restrain that growth with curative or palliative intention. The domain of antineoplastic chemotherapy is cancer that is disseminated and therefore not amenable to local treatment modalities such as surgery and radiotherapy. 

Cancer treatment is a multimodality treatment, i.e., surgery is combined with radiotherapy and antineoplastic chemotherapy. The latter treatment mode is used mainly for cancers which have disseminated. Different forms of cancer differ in their sensitivity to chemotherapy with antineoplastic agents. The most responsive include lymphomas, leukemias, choriocarcinoma and testicular carcinoma, while solid tumors such as colorectal, pancreatic and squamous cell bronchial carcinomas generally show a poor response. The clinical use of antineoplastic agents is characterized by the following principles. 

Intensive intermittent schedules of drug treatment should allow time for recovery from the acute toxic effects of antineoplastic agents, primarily bone marrow toxicity. The use of non-myelosuppressive agents can be considered during the recovery period, especially for treatment of fast-growing cancers. 

Platinum complexes (e.g., di-platinum, 8.100) are used as antineoplastic agents in the treatment of cancer. Their use is described in chapter 7. 

Mitomycin C is used as an antineoplastic agent and for slowing of fibroblast formation in open-angle glaucoma. Recently, mitomycin C has been used to induce tumor responses in patients with many types of cancer. For example, mitomycin C is used in the palliative treatment of various solid tumors such as nonsmall cell lung, cervical, colorectal, breast, bladder, pancreatic, and esophageal carcinomas. In addition to... 

This chapter introduces the basic concepts of carcinogenesis, tumor growth, and cancer treatment, provides general information on the pharmacology and clinical use of the antineoplastic agents, and presents an overview of supportive care issues in the oncology patient. 

Mitotane is an antineoplastic agent. The primary action is on the adrenal cortex. The production of adrenal steroids is reduced. The biochemical mechanism of action is nnknown. Data suggest that the drug modifies the peripheral metabolism of steroids and directly suppresses the adrenal cortex. Use of mitotane alters the peripheral metabolism of cortisol, even though plasma levels of corticosteroids do not fall. The drug causes increased formation of 6-beta-hydroxycortisol. Mitotane, a chlorophenothane (DDT) analog with antineoplastic properties (1 to 6 g p.o. daily in divided doses), is used in the treatment of inoperable adrenocortical cancer. 

Paclitaxel, an antineoplastic agent, is used in the treatment of metastatic ovarian cancer after failure of first-line or subsequent chemotherapy (135 mg/m IV over 24 hours q. 3 weeks) and breast carcinoma after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy (175 mg/m IV over 3 hours q. 3 weeks). 

It is the first ever antineoplastic agent that produced appreciable remissions in leukemia. It is extensively employed for the treatment of acute lymphoblastic leukemia. It is invariably used in combination cheotherapy for palliative management of limg eaneer, breast cancer and epidermoid cancers of the head. It is frequently recommended for the treatment and prophylaxis of meningeal leukemia based on its ability to penetrate the central nervous system. It is also of value in choricarcinoma and related trophoblastie tumours of women. 

This resonance-stabilized, mustard-like antineoplastic agent utilizes an estradiol carrier (Fig. 42.3) to selectively deliver drug to steroid-dependent prostate tissue, and its use is limited to the palliative treatment of progressive prostate cancer. The essential 17P-OH group has been esterified with phosphoric acid, and the C3-phenol has been carbamylated. The body still, however, transports the basic steroidal pharmacophore into cells. The ionized sodium phosphate ester of the active 17P-OH group makes the compound water soluble and able to distribute in the blood. The ester is readily cleaved during absorption to provide the active 17(3-OH. 

The loss of the 4-methoxy moiety also makes this compound more lipophilic than either doxorubicin or daunorubicin. This results in a better penetration into tumor cells and an enhanced antineoplastic potency. Increased rates of remission have been noted with the use of idarubicin compared to other anthracyclines antineoplastic agents. Unlike its congeners, idarubicin shows significant oral bioavailability and is lipophilic enough to penetrate the blood-brain barrier. Currently, however, it is given only by the IV route and is not used in the treatment of brain cancer. Its primary indication is in acute myeloid leukemia, and it is administered in combination with other antileukemic drugs. 

Many other alkaloid-based medicines exist. Drugs based on berberine are used in the treatment of infections as well as in the treatment of AIDS. The taxanes (e.g., paclitaxel in Taxol drug and its synthetic analogue, docetaxel in Taxotere) have antineoplastic agents to cure cancers, Kaposi s sarcoma, and squamous cell carcinomas. Several novel alkaloids and their synthetic analogues are under development and considered to being accepted by U.S. Food and Drug Administration for clinical use. ... 

N. poeticus and N. pseudonarcissus for this purpose. It is now known that N. poeticus contains 0.012% of the antineoplastic agent narciclasine (68) in the fresh bulb (14,101). Arabian, North African, and Chinese medical practitioners of the Middle Ages continued using Narcissus oil in cancer treatment (389). For example, bulbs of N. tazetta L. var. chinensis, cultivated in China as a decorative plant, were used topically for the treatment of tumors in folk medicine. In this case, pretazettine (64) was established to be one of the antitumor active compounds (133,390). The bulbs of N. tazetta continue to be used in Turkey as a home remedy for the treatment of abscesses because of their antiphlogistic and analgesic properties (391). 

Nevertheless, in some particular situations, CO can be considered a good choice for cancer treatment. Most of the data about CO s modulation of cell death indicate strong antiapoptotic properties, which is not compatible with chemotherapy strategies aiming the elimination of cancer cells. Thus, CORM-3 was used as an adjuvant in cancer therapy for limiting the antineoplastic agent cisplatin-induced nephrotoxicity [109], and CORM-2 was used for limiting doxorubicin-induced cardiotoxicity [79]. 

MTX is part of curative therapeutic schedules for acute lymphoblastic leukemias (ALL), Burkitt s lymphoma, and choriocarcinoma. It was also used in adjuvant therapy of breast cancer. High dose MTX with leucovorin rescue can induce about 30% remissions in patients with metastatic osteogenic sarcoma. MTX is one of the few antineoplastic drugs that can be safely administered intrathecally for the treatment of meningeal metastases and leukemic infiltrations (routine prophylaxis in ALL). In addition, MTX can be used as an immunosuppressive agent for the treatment of severe rheumatoid arthritis and psoriasis. 

Melphalan is an antineoplastic drug, listed also as a Class I immunosuppressive agent (effective only when given prior to the immune stimulus) [1]. It is used for the treatment of multiple myeloma, ovarian carcinoma, tumors of the testes, chronic granulocytic leukemia, chronic lymphocytic leukemia, seminoma, Ewing s sarcoma, reticulum cell sarcoma, and thymoma [1,2]. Its use as an adjuvant to surgery in the management of primary breast cancer was one of the first illustrations of the therapeutic potential of combined modalities of treatment [3]. 

---