The Carcinogenic Properties of Some of the Principal Drugs Used in Clinical Cancer Chemotherapy

Weisburger, John H.; Griswold, Daniel P.; Prejean, Joseph; Casey, Albert E.; Wood, Harry B.; Weisburger, Elizabeth K.

doi:10.1007/978-3-642-80940-8_1

Cited by 109 publications

(20 citation statements)

References 9 publications

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“…42 Alkylators, by alkylating DNA to disrupt cancer growth, may also cause DNA damage in normal tissue such that replication is impaired, placing those exposed at risk for solid tumors. 43 Our findings suggest potential gene-environment interactions causing SMN. Sarcoma (with the exception of Ewing sarcoma [EWS]) and leukemia are cancers known to be associated with LiFraumeni syndrome (LFS).…”

Section: Discussionmentioning

confidence: 71%

Breast Cancer Risk in Childhood Cancer Survivors Without a History of Chest Radiotherapy: A Report From the Childhood Cancer Survivor Study

Henderson

Moskowitz

Chou

et al. 2016

JCO

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Purpose Little is known about the breast cancer risk among childhood cancer survivors who did not receive chest radiotherapy. We sought to determine the magnitude of risk and associated risk factors for breast cancer among these women. Patients and Methods We evaluated cumulative breast cancer risk in 3,768 female childhood cancer survivors without a history of chest radiotherapy who were participants in the Childhood Cancer Survivor Study. Results With median follow up of 25.5 years (range, 8 to 39 years), 47 women developed breast cancer at a median age of 38.0 years (range, 22 to 47 years) and median of 24.0 years (range, 10 to 34 years) from primary cancer to breast cancer. A four-fold increased breast cancer risk (standardized incidence ratio [SIR] = 4.0; 95% CI, 3.0 to 5.3) was observed when compared with the general population. Risk was highest among sarcoma and leukemia survivors (SIR = 5.3; 95% CI, 3.6 to 7.8 and SIR = 4.1; 95% CI, 2.4 to 6.9, respectively). By the age of 45 years, the cumulative incidence of breast cancer in sarcoma and leukemia survivors was 5.8% (95% CI, 3.7 to 8.4) and 6.3% (95% CI, 3.0 to 11.3), respectively. No other primary cancer diagnosis was associated with an elevated risk. Alkylators and anthracyclines were associated with an increased breast cancer risk in a dose-dependent manner (P values from test for trend were both < .01). Conclusions Women not exposed to chest radiotherapy who survive childhood sarcoma or leukemia have an increased risk of breast cancer at a young age. The data suggest high-dose alkylator and anthracycline chemotherapy increase the risk of breast cancer. This may suggest a possible underlying gene-environment interaction that warrants further study.

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Section: Discussionmentioning

confidence: 71%

Breast Cancer Risk in Childhood Cancer Survivors Without a History of Chest Radiotherapy: A Report From the Childhood Cancer Survivor Study

Henderson

Moskowitz

Chou

et al. 2016

JCO

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“…Procarbazine is a potent carcinogen in rodents as well as in nonhuman primates; however, the tumors it induces in mice and rats are not ANLL, but instead are lung and mammary carcinomas and lymphocytic leukemia (12,39,40). As noted above, few experimental animals develop ANLL in response to carcinogen exposure.…”

Section: Procarbazinementioning

confidence: 99%

“…In one survey (67) (74) reported that melphalan increases the incidence of pulmonary tumors in strain A mice, and the drug was also found to increase the number of lung tumor nodules per mouse from a control level of 0.5 to 4.5 (75). Melphalan treatment also resulted in a significant increase in the incidence of peritoneal sarcomas in the CD rat (40). doses into perspective, women receiving prophylactic melphalan therapy for ovarian carcinoma would receive in the prescribed 18 month dosing period a total dose of 660 mg/M2 (76), a dose some 100-fold lower than that already ingested by these monkeys.…”

Section: Melphalanmentioning

confidence: 99%

“…Chlorambucil has carcinogenic activity in rodents, inducing lymphosarcomas and pulmonary and ovarian tumors in mice (40,74,75) and lymphomas in rats (40). In view of the numerous case reports in which prolonged chlorambucil treatment has been associated with the development of ANLL and the positive results with this drug in the rodent carcinogenesis bioassay, it is highly likely that chlorambucil is a human leukemogen.…”

Section: Chlorambucilmentioning

confidence: 99%

“…Moreover, ANLL has been reported to be the terminal event in five patients with multiple myeloma (71,72,113,114), two ovarian carcinoma patients (58), and four women with breast cancer (115). Cyclophosphamide has well-demonstrated carcinogenicity in rodents (40,74,75,116), and a study of its leukemogenic potential in nonhuman primates was recently initiated in this laboratory.…”

Section: Cyclophosphamidementioning

confidence: 99%

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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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1‐Acetyl‐2‐Picolinolhydrazine 17433‐31‐7

2004

Sax's Dangerous Properties of Industrial Materials

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The Carcinogenic Properties of Some of the Principal Drugs Used in Clinical Cancer Chemotherapy

Cited by 109 publications

References 9 publications

Breast Cancer Risk in Childhood Cancer Survivors Without a History of Chest Radiotherapy: A Report From the Childhood Cancer Survivor Study

Breast Cancer Risk in Childhood Cancer Survivors Without a History of Chest Radiotherapy: A Report From the Childhood Cancer Survivor Study

Chemically induced leukemia in humans.

1‐Acetyl‐2‐Picolinolhydrazine 17433‐31‐7

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