Epipodophyllotoxin-related leukemia: identification of a new subset of secondary leukemia

Article Abstract:

It is known that some chemotherapeutic agents are capable of causing cancer, as well as destroying it. The majority of cases of secondary cancer that have resulted from chemotherapeutic treatment have been caused by alkylating agents. This highly reactive group of chemical compounds works by reacting with DNA and adding methyl groups to its chemical structure. In a small number of cases these chemical reactions may cause a mutation that leads to cancer. However, evidence is accumulating that suggests other forms of chemotherapy may also cause cancer in a small fraction of cases. Nonalkylating chemotherapeutic agents that have been linked with cancer include etoposide and teniposide. These compounds are called epipodophyllotoxins and are derived from a substance that occurs naturally in plants. The epipodophyllotoxins work by inhibiting an enzyme called DNA topoisomerase II, which reversibly cleaves DNA chains as a part of a cell's normal management of the twisted and coiled DNA chain. When this enzyme is inhibited, DNA breaks accumulate, and the cell dies. In a recent case, a 22-month-old girl developed a mass in the lower spine that was diagnosed as a yolk-sac tumor. Treatment with vinblastine, bleomycin, cisplatin, and etoposide was successful. However, a little more than one year later the child developed acute monoblastic leukemia. The patient remains in remission 15 months after chemotherapy for the leukemia. This case adds to the 36 cases already published in the medical literature in which leukemia developed in a patient treated with etoposide or teniposide. The cases differed from the secondary leukemias that follow treatment with alkylating agents. In the reviewed cases, leukemia developed an average of 33 months after epipodophyllotoxin use, and an average of 58 to 73 months after alkylating agents. The leukemia following epipodophyllotoxin use was usually of the monocytic or myelomonocytic type. A particular chromosome abnormality seems to be especially common among these patients; about half of the cases had some abnormality involving chromosome 11, specifically 11q23. It is not yet known if the agents commonly used with epipodophyllotoxins, such as cisplatin, might enhance the development of leukemia. (Consumer Summary produced by Reliance Medical Information, Inc.)

Causes of, Complications and side effects, Leukemia, Chemotherapy, Etoposide, Podophyllotoxin

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Comprehensive management of disseminated breast cancer

Article Abstract:

In advanced disease, breast cancer cells may metastasize to the brain, lungs, bone, and liver. By the time that this dissemination of cancer cells has occurred, there is little likelihood of survival, and treatment is best thought of as palliative. Bone metastases, in particular, may be especially painful, and chemotherapy may result in a substantial improvement in the patient's quality of life if the pain can be substantially reduced. Unfortunately, the evaluation of the contribution of chemotherapy to the quality of life in a mortally ill patient is severely hampered by both the absence of objective measures and unreliable patient compliance. Some studies, however, have managed to show that the palliative results obtained from endocrine therapy, such as tamoxifen, are just as good as those obtained from cytotoxic chemotherapy when the patients are properly selected. In a group of randomly selected patients, those with estrogen-receptor negative cells were unlikely to respond to tamoxifen, and thus in any comparison of chemotherapy and endocrine therapy, the chemotherapy may have the edge. However, some patients are well suited to endocrine therapy, and these patients may be identified in advance. Patients with a long disease-free interval are more likely to respond to endocrine therapy, as are those whose metastatic disease is limited to bone and soft tissue. Among premenopausal women, those in their 40s are better candidates for endocrine therapy than younger patients, and women in the first five years after menopause are poorer candidates for endocrine therapy. An important unanswered question involves the timing of palliative treatment. Should palliative treatment be used in asymptomatic patients? Patients often desire to be treated, even when symptoms are minimal, but it is hard to justify the use of therapies that might be very important for the alleviation of symptoms later in the progression of the disease. A study is underway to determine if using experimental or unproven treatments during asymptomatic periods, and saving conventional therapy for when it is truly needed have a beneficial effect on the overall quality of life of the dying breast cancer patient. (Consumer Summary produced by Reliance Medical Information, Inc.)

Care and treatment, Drug therapy, Breast cancer

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