Toxicity of Antineoplastic Agents in Man: Chromosomal Aberrations, Antifertility Effects, Congenital Malformations, and Carcinogenic Potential

Sieber, S. M.; Adamson, Richard H.

doi:10.1016/s0065-230x(08)60176-1

Cited by 250 publications

(57 citation statements)

References 312 publications

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“…This is likely to be due to anovulation following more intensive treatment. Studies have shown that the ovary has fewer primordial follicles following chemotherapy (Sieber and Adamson, 1975). Many patients experience a period of anovulation following the EMA/CO treatment regimen.…”

Section: Time To Conception and Termination Ratementioning

confidence: 99%

“…This is often because they were keen to start or continue their family when they developed their original tumour. However, they are routinely advised to avoid pregnancy for at least 1 year post chemotherapy because: (1) most relapses occur in the first year post-treatment and these relapses are detected by a rising hCG secreted by the tumour cells (a normal pregnancy also produces hCG and this acts as a smoke screen masking the detection of tumour relapse); (2) the potential risk of cytotoxic drug induced damage to the ova (Sieber and Adamson, 1975;Schilsky et al, 1980;Choo et al, 1985); (3) the potentially increased risk of pregnancy induced relapse.…”

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confidence: 99%

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The effect of early pregnancy following chemotherapy on disease relapse and foetal outcome in women treated for gestational trophoblastic tumours

et al. 2002

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Little literature exists on the safety of early pregnancy following chemotherapy. Here we assess the rate of relapse and foetal outcome in women who have completed single and multi-agent chemotherapy for gestational trophoblastic tumours. The records of 1532 patients treated for persistent gestational trophoblastic tumours at Charing Cross Hospital between 1969 and 1998 were reviewed. Patients were defined as receiving single agent or multi-agent treatment. Relapse rates and foetal outcome were reviewed in the 230 patients who became pregnant within 12 months of completing chemotherapy. In the single agent group 153 (22%) of 691 patients conceived early. Three subsequently relapsed. In the multi-agent group, 77 (10%) of 779 patients conceived early, two then relapsed. Relapse rates were 2% (3 out of 153) and 2.5% (2 out of 77) for each group compared to 5% and 5.6% in the comparative non-pregnant groups. Outcomes of 230 early pregnancies: 164 (71%) delivered at full term, 35 (15%) terminations, 26 (11%) spontaneous abortions, three (1.3%) new hydatidiform moles and two (1%) stillbirths. Early pregnancies were more common in the single agent group (P50.001), but spontaneous miscarriages and terminations were more likely to occur in the multi-agent group (P=0.04 and 0.03, respectively). Of the fullterm pregnancies, three (1.8%) babies were born with congenital abnormalities. Patients in either group who conceive within 12 months of completing chemotherapy are not at increased risk of relapse. Though, we still advise avoiding pregnancy within 12 months of completing chemotherapy, those that do conceive can be reassured of a likely favourable outcome.

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Section: Time To Conception and Termination Ratementioning

confidence: 99%

mentioning

confidence: 99%

The effect of early pregnancy following chemotherapy on disease relapse and foetal outcome in women treated for gestational trophoblastic tumours

et al. 2002

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“…During the past decade, approximately 150 case reports of ANLL developing after treatment with cancer chemotherapeutic agents have appeared in the literature (14). The great majority of these leukemias were morphologic variants of acute myelogenous or myelomonocytic leukemia, and developed after exposure to various alkylating agents either given as single agents or in combination with other drugs.…”

Section: Chemicals Implicated As Leukemogens In Humansmentioning

confidence: 99%

Chemically induced leukemia in humans.

Adamson¹,

Seiber²

1981

Environ Health Perspect

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The human population may be exposed to potentially leukemogenic agents, either in the form of drugs and food additives or as environmental contaminants and pollutants. However, in spite of the large number and diversity of these chemicals, only a few have been implicated as human leukemogens. One such agent is benzene, a known bone marrow depressant. A number of case reports have associated chronic exposure to this agent with the development of acute leukemia, as have several epidemiologic surveys. Treatment with various antitumor agents, including procarbazine, melphalan, thio-TEPA, chlorambucil, and cyclophosphamide, has also been associated with the development of acute leukemia. In addition, chloramphenicol and phenylbutazone have been implicated as human leukemogens, but the association between exposure to these two agents and acute leukemia appears at present to be weaker than it is for benzene and antitumor agent exposure. Despite such associations between exposure to chemicals and acute leukemia, several important problems exist with regard to implicating specific agents in the development of this neoplasm in man, including the paucity of animal models for chemically induced leukemia, and the frequent necessity to rely on single case reports or clusters of cases in which chemical exposures are associated with acute leukemia. Future efforts should be directed at performing properly designed and well executed epidemiologic studies, and at developing new in vitro and in vivo models for the study of this neoplasm.

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“…Alkylating agents such as cyclophosphamide have been reported to inhibit the growth of follicles, to destroy small oocytes and to induce gonadal atrophy and amenorrhoea (Sieber and Adamson, 1975;Sobrinho et al, 1971;Warne et al, 1973;Miller et al, 1971;Miller & Cole, 1970). Cytotoxic drugs inhibit cell proliferation and growth in actively growing cells through action on different phases of the cell cycle (Spiers, 1974).…”

Section: Discussionmentioning

confidence: 99%

“…Childhood leukaemia is treated with corticosteroids and cytotoxic agents. Several of these drugs are reported to induce gonadal atrophy and amenorrhoea in women (Sieber and Adamson, 1975). During the last decade, an increasing number of children with leukaemia have been successfully treated and reach adulthood.…”

mentioning

confidence: 99%

Morphological study of the ovaries of leukaemic children

Himelstein-Braw¹,

Peters²,

Faber³

1978

Br J Cancer

145

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Summary.-The ovaries of leukaemic children were studied in 31 specimens obtained at autopsy. Twenty-eight ovaries from normal children of the same age who died from misadventure served as control. All ovaries from normal children showed follicle growth and contained several large antral follicles.Follicle development was inhibited in all ovaries of leukaemic children; 22% showed no follicle growth (quiescent ovaries), and in the ovaries in which there was follicle development, the number and size of antral follicles was significantly smaller than in the control. All children had been treated with cytotoxic drugs, the duration of the treatment being correlated with the stage of ovarian development. The ovaries of children treated for only 1 week were near-normal, while those treated for more than 2 months showed inhibition of follicle growth. It is argued that the disturbance in follicle development is an effect of the cytotoxic drugs, and not an effect of the disease itself.

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Toxicity of Antineoplastic Agents in Man: Chromosomal Aberrations, Antifertility Effects, Congenital Malformations, and Carcinogenic Potential

Cited by 250 publications

References 312 publications

The effect of early pregnancy following chemotherapy on disease relapse and foetal outcome in women treated for gestational trophoblastic tumours

The effect of early pregnancy following chemotherapy on disease relapse and foetal outcome in women treated for gestational trophoblastic tumours

Chemically induced leukemia in humans.

Morphological study of the ovaries of leukaemic children

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