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Podophyllotoxin is a non-alkaloid toxin lignan extracted from the roots and rhizomes of Podophyllum species. Under the trade name Condylox, a topical gel, it is used on the skin to treat external genital warts, caused by some types of the human papillomavirus.

The derivatives Etoposide  and teniposide  are used in chemotherapy.  Both exploit the normal mechanism of action of the enzyme topoisomerase II, which aids in DNA unwinding, and by doing so causes DNA strands to break. Cancer cells rely on this enzyme more than healthy cells, since they divide more rapidly

• Etoposide phosphate  - brand names: Eposin, Etopophos, Vepesid , VP-16. It is used for cancers such as Ewing's sarcoma, lung cancer, testicular cancer, lymphoma, non-lymphocytic leukemia, and glioblastoma multiforme. It is often given in combination with other drugs. It is also sometimes used in a conditioning regimen prior to a bone marrow or blood stem cell transplant.

• Teniposide (Vumon) is a chemotherapeutic medication mainly used in the treatment of childhood acute lymphocytic leukemia.

Remembering that the patients are dying of their cancers anyway, the side effects of chemotherapy with these drugs is often considered a ‘necessary evil’, however, they are severe, for example…………

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Side effects of chemotherapy for advanced urothelial carcinoma with etoposide and ifosfamide. - Müller M, Heicappell R, Steiner U, Goessl C, Miller K; Department of Urology, Universitätsklinikum Benjamin-Franklin, Freie Universität Berlin, Germany.

OBJECTIVES:  To date, chemotherapy for advanced urothelial carcinoma has been associated with only moderate therapeutic success and minimal extension of survival. This, coupled with the occurrence of serious side effects and the resulting reduced quality of life, underscores the need for new chemotherapeutic agents. A first study investigating combination therapy with etoposide and ifosfamide reported not only comparable therapeutic effectiveness but, due primarily to the elimination of the cisplatin component, a reduction in nephrotoxic side effects. In the present study, therefore, patients with advanced urothelial carcinoma and minor compromised renal function received combination chemotherapy with etoposide and ifosfamide.

METHODS:  Fourteen patients with advanced urothelial carcinoma underwent chemotherapy with a combination of etoposide and ifosfamide. On days 1-5, patients received 1,500 mg/m2 ifosfamide and 120 mg/m2 etoposide. The next corresponding cycle was started on day 22.

RESULTS:  A number of serious side effects were observed. These consisted predominantly of high-grade myelosuppression requiring therapy, as well as disturbances in the central nervous system and impairment of renal function. Due to severe side effects, chemotherapy had to be prematurely terminated in 8 of 14 patients (57%). The efficacy of therapy, however, was observed in patients completing the treatment regimen.

CONCLUSIONS:  The new combined chemotherapy with etoposide and ifosfamide shows efficacy in the treatment of advanced urothelial carcinoma. This, however, is overshadowed by the high rate of serious side effects leading to premature interruption of therapy.