Testicular carcinomas

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. 

The most widely used drug in this category is cisplatin. Therfeore, we have summarized below its action at the chromatin level. The anti-tumour drug cis-diamminedichloroplatinum(II) (cisplatin) is employed for the treatment of ovarian and testicular carcinomas, as well as solid tumours (Loehrer and Einhorn, 1984 Zamble and Lippard 1995). 

Bleomycin, in combination with cisplatin or etopo-side, is important as part of the potentially curative combination chemotherapy of advanced testicular carcinomas. Bleomycin is used in some standard regimens for the treatment of Hodgkin s and non-Hodgkin s lymphomas, and it is useful against squamous cell carcinomas of the head and neck, cervix, and skin. 

Plicamycin (mithramycin, Mithracin) is one of the chro-momycin group of antibiotics produced by Streptomyces tanashiensis. Plicamycin binds to DNA and inhibits transcription. It also inhibits resorption of bone by osteoblasts, thus lowering serum calcium levels. Very little is known about its distribution, metabolism, and excretion. Because of its severe toxicity, plicamycin has limited clinical utility. The major indication for plicamycin therapy is in the treatment of life-threatening hypercalcemia associated with malignancy. Plicamycin also can be used in the palliative therapy of metastatic testicular carcinoma when all other known active drugs have failed. 

Advanced testicular carcinoma Hodgkin s and non-Hodgkin s lymphomas squamous cell carcinoma of head, neck, cervix, skin Prostatic cancer Chronic granulocytic leukemia Testicular and ovarian cancer... 

Unlabeled Uses Adrenocortical, bladder, cervical, endometrial, prostatic, testicular carcinomas Ewing s sarcoma multiple sclerosis non-small cell, small cell lung cancer organ transplant rejection osteosarcoma ovarian germ cell, primary brain, trophoblastic tumors rheumatoid arthritis soft tissue sarcomas systemic dermato-myositis systemic lupus erythematosus Wilms tumor... 

Uniabeied Uses Treatment of acute myelocytic leukemia bladder, cervical, ovarian, prostatic, renal, and testicular carcinomas psoriatic arthritis systemic dermatomyo-sitis... 

It is indicated in Hodgkin s and non Hodgkin s lymphoma, testicular carcinoma, mycosis fungoides and Kaposi s sarcoma. 

Bleomycins are a group of glycopeptide antibiotics that degrade preformed DNA. Bleomycin is used in the treatment of testicular carcinoma, sarcomas, and carcinomas of the oesophagus and lung. In contrast to most anticancer drugs, bleomycin causes little myelotoxicity. It is... 

Plicamycin Mithracin Testicular carcinoma Blood disorders [leukopenia, thrombocytopenia] Gl distress [nausea, vomiting, diarrhea, Gl tract irritation] general weakness and malaise... 

Bleomycin (Blenoxane) causes chain scission and fragmentation of DNA. With the exception of the skin and lungs, most tissues can enzymatically inactivate bleomycin. Bleomycin is used in the management of squamous cell carcinoma of the head, neck, and esophagus in combination with other drugs in patients with testicular carcinoma, and in the treatment of Hodgkin s disease and other lymphomas. Bleomycin causes stomatitis, ulceration, hyperpigmentation, erythema, and pulmonary fibrosis. 

Almstrup K, Ottesen AM, Sonne SB, Hoei-Hansen CE, Leffers H, Rajpert-De Meyts E, et al. Genomic and gene expression signature of the pre-invasive testicular carcinoma in situ. Cell Tissue Res 2005 322(1) 159-165. 

Therapeutic applications Cisplatin has found wide application in the treatment of solid tumors such as metastatic testicular carcinoma in combination with vinblastine (see p. 390) and bleomycin (see p. 386), ovarian carcinoma in combination with cyclophosphamide (see p. 388), or alone for bladder carcinoma. Carboplatin is employed when patients cannot be vigorously hydrated as is required for cisplatin treatment, or if they suffer from kidney dysfunction or are prone to neuro- or ototoxicity. 

Platinum coordination complexes have been investigated as potential anticancer agents since 1972. The most successful of these is the cis dichlor-diammine platinum(II) complex which is particularly effective for the treatment of ovarian and testicular carcinomas. However, effective therapy requires high doses, typically 4.0/umol (825/ig)kg-1 given intravenously, which produce unpleasant and toxic reactions. Pharmaco-kinetic studies of the various Pt species in plasma indicate that the active species is of low molecular weight and the protein bound Pt species is apparently inactive [106]. Further work is needed to identify the active species and to develop therapeutic procedures that produce maximum anti-tumour activity with minimum toxicity. 

Kennedy BJ, Torkelson J, Fraley EE. Optimal number of chemotherapy courses in advanced nonseminomatous testicular carcinoma. Am J Chn Oncol 1995 18(6) 463-8. 

Meijer S, Mulder NH, Sleijfer DT, de Jong PE, Sluiter WJ, Schraffordt Koops H, van der Hem GK. Nephrotoxicity of cis-diam-minedichloride platinum [CDDP] during remission-induction and maintenance chemotherapy of the testicular carcinoma. Cancer Chemother Pharmacol 1982 8 27-30. 

Indications Melanomas, sarcomas, lymphomas, testicular carcinoma... 

Sonne SB, Herlihy AS, Hoei-Hansen CE, et al. Identity of M2A (D2-40) antigen and gp36 (Aggrus, TlA-2, podoplanin) in human developing testis, testicular carcinoma in situ and germcell tumours. Virchows Arch. 2006 449 200-206. 

Hoei-Hansen CE, Nielsen JE, Almstrup K, et al. Transcription factor AP-2gamma is a developmentally regulated marker of testicular carcinoma in situ and germ cell tumors. Clin Cancer Res. 2004 10 8521. 

The drug presently has its main carcinolytic indication in the treatment of testicular carcinoma. An unrelated effect, probably on osteoclast bone cells, leads to a significant reduction of plasma calcium at one-tenth the antineoplastic dose. This has been useful in hypercalcemia of malignancy, Paget s disease, and hyperparathyroid conditions. 

Dactinomycin is an antineoplastic agent that is the principal component of the mixture of actinomycins produced by Streptomyces parvullus. It inhibits messenger RNA synthesis. Dactinomycin (0.5 mg/day IV for 5 days), in combination with vincristine, radiotherapy, and surgery, is used in Wilms tumor in conjunction with vincristine, cyclophosphamide, and doxorubicin, it is used in choriocarcinoma in combination with methotrexate, it is used in testicular carcinoma and in combination with cyclophosphamide and radiotherapy, it is used in Ewing s sarcoma. Dactinomycin inhibits messenger RNA synthesis by anchoring to a purine-pyrimidine (DNA) base pair by intercalation (see Figure 15). The toxicity of dactinomycin increases when combined with radiation therapy. 

Etoposide (70 mg/m /day p.o.) is an antineoplastic agent that is indicated in smaU-ceU carcinoma of the lung and testicular carcinoma. Etoposide exerts its cytotoxic action by arresting cells in the metaphase portion of cell division. The drug also inhibits cells from entering mitosis and depresses DNA and RNA synthesis (see also Figure 15). 

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