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Effects of Chemotherapy on Pregnancy for Survivors of Childhood Cancer Treated Between 1970 and 1999

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Key Points

  • Receipt of alkylating chemotherapy was associated with a reduced likelihood of pregnancy for both male and female survivors, according to an analysis in the Childhood Cancer Survivor Study cohort.
  • Associations with dose were observed for cyclophosphamide, ifosfamide, procarbazine, and cisplatin among males and for busulfan and lomustine among females.

In an analysis in the Childhood Cancer Survivor Study cohort reported in The Lancet Oncology, Chow et al found that increasing doses of several alkylating agents reduced the likelihood of fathering a pregnancy among male survivors of childhood cancer, with fewer drug associations with pregnancy observed among female survivors.

Study Details

The study involved data from 10,938 5-year survivors of the most common types of childhood cancer who were diagnosed before age 21 years and treated at 27 sites in the United States and Canada between 1970 and 1999 and who were not exposed to pelvic or cranial radiotherapy. Doses of 14 alkylating agents and cumulative cyclophosphamide equivalent doses were assessed in relation to pregnancies and live births occurring between the ages of 15 and 44 years. A total of 3,949 patient siblings were included as a comparison group.

Pregnancy and Live Birth

After a median follow-up of 8 years from the later of cohort entry or age 15 years, 4,149 survivors (38%) reported having or fathering a pregnancy, with 3,453 (83%) reporting at least one live birth. After a median follow-up of 10 years, 2,445 (62%) reported a pregnancy, with 2,201 (90%) reporting at least one live birth.

In multivariate analysis, both male survivors (hazard ratio [HR] = 0.63, P < .0001) and female survivors (HR = 0.87, P < .0001) had reduced likelihood of fathering or having a pregnancy, and both male survivors (HR = 0.63, P < .0001) and female survivors (HR = 0.82, P < .0001) had a reduced likelihood of having a live birth.

Dose Associations

Among male survivors, a reduced likelihood of pregnancy was associated with upper-tertile doses of cyclophosphamide (HR = 0.60, P < .0001), ifosfamide (HR = 0.42, P = .0069), procarbazine (Matulane; HR = 0.30, P < .0001), and cisplatin (HR = 0.56, P = .0023), with a cyclophosphamide equivalent dose being significantly associated with a decreased likelihood (HR = 0.82, P < .0001, per 5,000 mg/m2 increment).

Among female survivors, busulfan (HRs = 0.22, P = .020, for < 450 mg/m2, and 0.14, P = .0051, for ≥ 450 mg/m2) and lomustine (Gleostine; HR = 0.41, P = .046, for ≥ 411 mg/m2) were significantly associated with a reduced likelihood of pregnancy, with a cyclophosphamide equivalent dose being associated with a significantly reduced likelihood only for comparison of upper quartile vs no exposure (HR = 0.85, P = .023). Findings for live birth were similar to those for pregnancy.

The investigators concluded: “Greater doses of contemporary alkylating drugs and cisplatin were associated with a decreased likelihood of siring a pregnancy in male survivors of childhood cancer. However, our findings should provide reassurance to most female survivors treated with chemotherapy without radiotherapy to the pelvis or brain, given that chemotherapy-specific effects on pregnancy were generally few. Nevertheless, consideration of fertility preservation before cancer treatment remains important to maximise the reproductive potential of all adolescents newly diagnosed with cancer.”

The study was funded by the National Cancer Institute, the National Institutes of Health, and American Lebanese–Syrian Associated Charities.

Eric J. Chow, MD, of Fred Hutchinson Cancer Research Center, is the corresponding author of The Lancet Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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