Testicular tumors, treatment

Mithramycin (also known as MIT and plicamy-cin) is an antibiotic that binds to DNA to regulate transcription. It attaches to specific regions of DNA that are rich in guanine and cytosine. It appears to lower serum calcium concentrations by blocking the hypercalcemic action of Vitamin D. After IV administration about 25% of the drug is excreted in the urine after 2 hours, and 40% after 15 hours. The main indications are treatment of testicular tumors and control of hypercalcemia and hypercalciuria. 

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 observation that fractions of the rosey periwinkle, Catharanthus rosea, produced severe leukopenia, resulted in the isolation and development of two major anticancer drugs, vincristine and vinblastine. These two complex, dimeric indole-indoline alkaloids are important in the treatment of acute childhood leukemia (vincristine), Hodgkin s disease (vinblastine), and metastatic testicular tumors (vinblastine), and continue to be manufactured today by mass cultivation and processing of their natural source. 

A reduced capacity to repair cisplatin-DNA adducts may be responsible for the clinical effectiveness of the drug in the treatment of certain types of cancer. Cell lines derived from human testicular tumors are hypersensitive... 

Therapeutic applications Bleomycin is primarily employed in the treatment of testicular tumors in combination with vinblastine (see p. 390) or etoposide (see p. 397). Response rates are close to... 

Although many other alkaloids have been isolated from C. roseus only vinblastine and vincristine have been developed for clinical use. The antiproliferative activity of the two compounds is related to their specific interaction with tubulin, thus preventing assembly of tubulin into microtubules and arresting cell division (59). However, despite this apparent identical mechanism of action and their clear chemical similarities, vinblastine and vincristine display very different clinical effects. Vinblastine, for example, is used to treat Hodgkin s disease and metastatic testicular tumors, whereas vincristine is used mainly in combination with other anticancer drugs for the treatment of acute lymphocyticleukemia in children. Toxicity profiles are also different, in that vinblastine causes bone-marrow depression, whereas peripheral neuropathy often proves to be dose-limiting in vincristine therapy. 

Etoposide is used primarily in treatment of testicular tumors in combination with bleomycin and cispiatin, and in combination with cispiatin and ifosfamide for small-cell carcinoma of the lung. It also is active against non-Hodgkin s lymphomas, acute nonlymphocytic leukemia, and Kaposi s sarcoma associated with AIDS. Etoposide has a favorable toxicity profile for dose escalation in that its primary acute toxicity is myelosuppression. In combination with ifosfamide and carboplatin, it is frequently used for high-dose chemotherapy in total doses of 1500 to 2000 mg/m. ... 

A semisynthetic podophyllotoxin derivative, VP 16213 (etoposide), has been approved in the United States as a chemotherapeutic agent (often in combination regimes with cisplatin, bleomycin, and others) for the treatment of refractory testicular tumors and for the treatment of small cell lung cancer. VM26 (teniposide) is being investigated for the treatment of acute lymphoblastic leukemia, various lymphomas, and other carcinomas. Semisynthetic derivatives are being used in Europe for the treatment of psoriasis and rheumatoid arthritis. 

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. 

Bleomycin is partially inactivated by bleomycin hydrolase present in various tissues. Some bleomycin-resistant cells contain high levels of hydrolase activity. Bleomycin is used in combination regimens for the treatment of lymphomas and in treating testicular, ovarian cancers and other solid tumors. 

The application of these principles is well illustrated in the current approach to the treatment of acute leukemia, lymphomas, Wilms tumor, and testicular neoplasms. 

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). 

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