Choriocarcinoma, treatment

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. 

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. 

Its mechanism of action is based on intercalation in the minor groove of double stranded DNA, interference with RNA polymerase and with topoiso-merase II. Its primary indications are rhabdomyosarcoma and Wilms tumor in children. In combination with methotrexate, it is used in the treatment of choriocarcinoma. 

Dactinomycin is used in curative combined treatment of Wilms tumor, Ewing s sarcoma, rhabdomyosarcoma, and gestational choriocarcinoma. It is active in testicular tumors, lymphomas, melanomas, and sarcomas, although its use in most of these malignancies has been supplanted by other agents. 

The antibiotics that bind to DNA are nonspecific to the cell-cycle phase. Dactinomycin (actinomycin D and Cosmegen) binds to double-stranded DNA and prevents RNA synthesis by inhibiting DNA-dependent RNA polymerase. It is administered intravenously in the treatment of pediatric solid tumors such as Wilms tumor and rhabdomyosarcoma and for gestational choriocarcinoma. Dactinomycin causes skin reactions, gastrointestinal injury, and delayed bone marrow depression. 

Therapeutic modalities in cancer treatment may involve surgery, radiation, and/or chemotherapy. The objectives of cancer chemotherapy include (1) cure, (2) reduction in tumor size, and (3) prolongation of life. At the present time, approximately 50 percent of patients with cancer can be cured, with drug treatment estimated to contribute in 17 percent of cases. Cancer chemotherapy can be curative in testicular cancer, diffuse large cell lymphoma, Hodgkin s disease, choriocarcinoma, certain childhood tumors (acute lymphoblastic leukemia, Burkitt s lymphoma, Wilms tumor, and embryonal rhabdomyosarcoma). Certain cancers are more resistant to chemotherapy than others (e.g., lung and colon). 

Therapeutic applications Dactinomycin is used in combination with surgery and vincristine (see p. 390) for the treatment of Wilm s tumor. With methotrexate (see p. 378) it is effective in the treatment of gestational choriocarcinoma. Some soft-tissue sarcomas also respond. 

Methotrexate is a valuable drug in the treatment of many rapidly growing tumors, such as those in acute leukemia and choriocarcinoma, a cancer derived from placental cells. However, methotrexate kills rapidly replicating cells whether they are malignant or not. Stem cells in bone marrow, epithelial cells of the intestinal tract, and hair follicles are vulnerable to the action of this folate antagonist, accounting for its toxic side effects, which include weakening of the immune system, nausea, and hair loss. 

In relation to immunoassays, interference from proteins (usually antibodies) should be recognized. Ismail et aft found in a survey comprising more than 5000 TSH results that interference occurred in 0.5% of the samples, leading to incorrect results that in a majority of the cases could have changed the treatment. Rotmensch and Cole" described 12 patients in whom a diagnosis of postgestational choriocarcinoma was made based on false-positive test results for... 

Folate analogues, such as methotrexate (Figure 27-3), are folate antagonists. They block production of FH2 and FH4 by dihydrofolate reductase and lead to diminished purine biosynthesis (inhibition of reactions 3 and 9 in Figure 27-8). Methotrexate also affects metabolism of amino acids and pyrimidine (inhibition of thymidylate synthesis) and inhibits DNA, RNA, and protein synthesis. It is effective in the treatment of breast cancer, cancer of the head and neck, choriocarcinoma, osteogenic sarcoma, and acute forms of leukemia. High doses of methotrexate can be tolerated provided that the patient also receives folinic... 

VINBLASTINE is administered i.v. once weekly in doses of 6 mg/m (up to 18 mg/ m body area) in the treatment of Hodgkin s disease and choriocarcinoma. 

In addition, 5-FU and methotrexate are used to treat certain forms of breast cancer, and methotrexate is the drug of choice for the treatment of choriocarcinoma in women. It is also effective in the treatment of psoriasis, a disease in which there is an over-proliferation of epidermal cells in the skin. Finally, it is worth recalling that azidothymidine (AZT) was first synthesised in 1964 as a potential anti-metabolite for cancer chemotherapy, but proved to be ineffective in this role. Its subsequent efficacy as an inhibitor of viral reverse transcriptase in the treatment of HIV infections has assured its place in the history of the 20th century. 

Actinomycin is particularly effective in the treatment of Wilm s tumor in the kidney (of children) and, as a member of combination protocols, against adult Ewing s and Kaposi s sarcoma. This agent is also useful in MTX-resistant choriocarcinoma. The drug is cell-cycle specific in the S and G, phase. 

The most important clinical use of dactinomycin is in the treatment of rhabdomyosarcoma and Wilms tumor in children, where it is curative in combination with primary surgery, radiotherapy, and other drugs, particularly vincristine and cyclophosphamide. Antineoplastic activity has been noted in Ewing s tumor, Kaposi s sarcoma, and soft-tissue sarcomas. Dactinomycin can be effective in women with advanced cases of choriocarcinoma in combination with methotrexate. Dactinomycin also has been used as an immunosuppressant in renal transplants. 

Antifolate chemotherapy occupies a Special place in the history of cancer treatment, as this class of drugs produced the first striking, although temporary, remissions in leukemia, and the first cure of a solid tumor, choriocarcinoma. These advances provided great impetus to the development of chemotherapy for cancer. Interest in folate... 

Vinblastine, with the commercial names Velbe , Velban and Vinblastine , is used alone and as a component of combined regimens with other anticancer drugs in the treatment of Hodgkin s disease and other lymphomas, in advanced carcinoma of the testis, in Kaposi s sarcoma and histiocytosis X. It can also be used in the treatment of breast carcinoma and choriocarcinoma. The use of vinblastine is mainly limited by its hematological toxicity due to destruction of the bone marrow [13-15]. 

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