Enzymes and antibodies exerting antineoplastic effects

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Asparaginase is a bacterial enzyme that is typically used in combination with other antineoplastic agents, to interfere with the availability of the amino acid asparagine to rapidly growing cancer cells. There have been seven case reports of pregnant women exposed to asparaginase during the second trimester (Turchi 1988, Scheuning 1987, Awidi 1983, Karp 1983, Okun 1979, Khurshid 1978). In each case, asparaginase was administered in combination with a number of other chemotherapeutic agents in the treatment of acute leukemias. No birth defects were noted in the offspring of these women, but two infants had transient bone marrow hypoplasia. One child was found to have chromosomal gaps and a ring chromosome.

Because multiple chemotherapeutic agents were involved in each pregnancy, no direct association with asparaginase exposure can be made.

Alemtuzumab, ibritumomab-tiuxetan, cetuximab, edrecolomab, bortezomib, and tositumomab arc monoclonal antibodies for which there are no data on tolerance during pregnancy.

There arc four reports on rituximab with apparently normal prcgnancy outcomes. Two treatments occurred inadvertently during the first trimester, the other from week 21 onwards (Ojeda-Uribe 2006, Kimby 2004, Herold 2001). The fourth patient, with a diffuse large B-celi lymphoma, was successfully treated with rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone, and filgastrim during the second trimester of pregnancy. At delivery of a premature but otherwise healthy girl the serum rituximab concentrations (half-life of 28 days) were similar in mother and child. The child's B cells were severely diminished at birth, but recovered faster than did those in the mother. Neither mother nor child developed any infections during the time of observation (Decker 2006).

Trastuzumab is a monoclonal antibody which blocks the "human epidermal growth factor 2" protein and has an estimated half-life of 12 days. Waterstone (2006) reported on an uneventful prcgnancy and the delivery of a healthy girl whose mother conceived 3 days after her second cyclc of trastuzumab. There is one case report of inadvertent exposure of a 28-year-old with breast cancer who was given the drug every 3 weeks until week 20 of her pregnancy. When, in week 23, the pregnancy was noticed, a lack of amniotic fluid prevailed with a healthy female fetus. Gradually, Lhe amount of amniotic fluid recovered. In week 37, a healthy girl was delivered whose kidney function was normal at the age of 6 months and who showed no sign of pulmonary hypoplasia (Watson 2005). There is another report regarding the development of an oligohydramnios after trastuzumab therapy. Fanale (2005) described a case where therapy with trastuzumab and vinorelbine was started after week 27 because of metastatic breast cancer. Despite extra hydration, the amniotic fluid indexes were low so that delivery was induced in week 35. The male infant was healthy, and no immediate postpartum neonatal complications were noted.

Gefitinib is still in the testing stage for small-cell bronchial carcinoma, and there are not yet any data on pregnancy. The same is true of lapatinib and bevacizumab. which are administered together with 5-fluorouracil to treat metastasizing colon or rectal carcinomas.

Aldesleukin is produced by genetic engineering in E. coli, and is used for the treatment of metastasizing renal cell carcinoma. There are no data concerning its use during pregnancy. This is also the case with lenalidomide, as therapeutic approach for myelodysplasia syndrome. Lenalidomide is structurally similar to thalidomide;

however, they have different developmental effects in animal experiments. In contrast to thalidomide, lenalidomide does not produce limb malformations in rabbits, but deaths, abortions and total litter losses (Christian 2006).

The liposomal cancer vaccine L-BLP25, against non-small-cell bronchial carcinoma, is still being tested in clinical trials, as is acti-nonin, an antibiotic with proliferation-inhibiting properties. There are obviously no data concerning use during pregnancy.

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