Early Age Onset Colorectal Cancer Chemotherapy During Pregnancy

Early Age Onset Colorectal Cancer: Chemotherapy During Pregnancy Cynthia Gail Leichman, MD March 19, 2016

Scope of the Problem • CRC is increasing in the younger population • Cancer during pregnancy is increasing • Expected further increase with trend to delay pregnancy to later age

Chemotherapy During Pregnancy ISSUES: • Clinical suspicion for diagnosis – Overlapping pregnancy symptoms may yield later diagnosis • Stage and type of cancer and goals of therapy – Adjuvant, Disseminated • Stage of pregnancy – Trimester specific toxicity – Effect of pregnancy on maternal prognosis • Specific toxicities – Choice of therapy • Chemical, Biologic, ? Immunotherapy • Combinations of different drug classes – Ancillary medications • Support – Siblings, spouse

Chemotherapy During Pregnancy RISKS OF CHEMOTHERAPY DURING PREGNANCY • Fetal risks – First Trimester: – Spontaneous abortion, fetal death, major malformations – 10 -25% risk major malformation; higher with combination than single agent therapy • Fetal risks – Second and Third Trimester – Intrauterine growth retardation (IUGR), low birth weight, and premature delivery – Estimates: 7% IUGR, 5% premature delivery, 6% fetal or neonatal death (N=376)

Chemotherapy During Pregnancy Maternal Risk: • Impaired survival secondary to treatment delay • Enhanced physical stress of pregnancy and chemotherapy toxicity • Enhanced psychosocial stress Maternal and Fetal Risk: • Myelosuppression at delivery

Chemotherapy During Pregnancy GENERALLY ACCEPTED PRINCIPLES • Health of the mother should come first • Chemotherapy should be avoided in first trimester to avoid congenital malformation • Non-obstetrical surgery may be performed during pregnancy without increased adverse outcome • In most cancers, pregnancy doesn’t adversely affect maternal prognosis compared to matched non-pregnant cancer patients

Chemotherapy During Pregnancy WHAT DATA DO WE HAVE TO GUIDE DECISIONS? • Likely few cases for any single oncologist – 0. 02% to 0. 1% of all pregnancies – 1 cancer per 1000 pregnant women • Can mammalian animal data help? – Available preclinically for all new drugs – Human dosing likely. Pereg, lower et al ; Cancer Treatment Reviews 2008

Chemotherapy During Pregnancy WHAT DATA DO WE HAVE TO GUIDE DECISIONS? • Case reports and retrospective studies – Summary by chemotherapy agents; Summary by cancer type • Numbers range between 3 -150 pregnancies – Impacted by publication bias • Adverse outcome more likely reported • Favorable outcome less likely published – Lack long term follow-up • Incomplete understanding of long-term cognitive, cardiac, psychologic development; risk of subsequent malignancies • Registries and Databases – Few

Chemotherapy During Pregnancy November 5, 2015

Chemotherapy During Pregnancy Study Overview • Fetal exposure to maternal cancer during pregnancy with or without treatment did not have an adverse effect on cognitive, cardiac, or general development in early childhood.

Chemotherapy During Pregnancy Study Design and Recruitment. 3 CRC Amant F et al. N Engl J Med 2015; 373: 1824 -1834

Chemotherapy During Pregnancy Characteristics of the Children at Baseline. Birth weight below 10 th percentile (small for gestational age): • 28/127 (22. 0%) in prenatal exposure group • 19/125 (15. 2%) in control group • P=0. 16 Amant F et al. N Engl J Med 2015; 373: 1824 -1834

Chemotherapy During Pregnancy Cancer Treatment during Pregnancy for All Children and Those Categorized as Small for Gestational Age. Amant F et al. N Engl J Med 2015; 373: 1824 -1834

Chemotherapy During Pregnancy Cognitive Outcome. Bayley Scales of Infant Development: • Motor and Verbal Skills • Scores range 50 -150 • Higher score = more development • Mean=100+/-15; <85= developmental delay • Gestational age relates to cognitive score in both groups (2 A) • Average cognitive score increases 2. 9 points for each additional week in gestational age at birth Amant F et al. N Engl J Med 2015; 373: 1824 -1834

Chemotherapy During Pregnancy Echocardiographic Data and Other Measurements of Cardiac Function at 36 Months. Amant F et al. N Engl J Med 2015; 373: 1824 -1834

Chemotherapy During Pregnancy Conclusions • Prenatal exposure to maternal cancer with or without treatment did not impair the cognitive, cardiac, or general development of children in early childhood. • Prematurity was correlated with a worse cognitive outcome, but this effect was independent of cancer treatment.

Chemotherapy During Pregnancy IN CONCLUSION: • Given according to the best available data, appropriate treatment for maternal cancer appears to be safe in 2 nd and 3 rd trimesters for both mother and fetus. • The ultimate decision is individual to the patient – based on informed discussion with her family and her multidisciplinary care team • We need to continue to improve upon the best available data to provide to our patients to aid in these decisions • Continued development of registries into which ALL data is entered is essential to accomplishing this goal

Chemotherapy During Pregnancy References 1. Cardonick E, Iacobucci A. Use of chemotherapy during human pregnancy. The Lancet Oncology, 5: 283 -91; 2004. USA 2. Pereg D, Koren G, Lishner M. Cancer in pregnancy: gaps, challenges, and solutions. Cancer Treatment Reviews, 34: 302 -12; 2 EUR 3. Amant F, Vandenbroucke M, Verheecke M, et. al. for the International Network on Cancer, Infertility and Pregnancy (INCIP). Pediatric outcome after maternal cancer diagnosed during pregnancy. N Engl J Med 373: 1824 -34; 2015. EUR 4. Koren G, Carey N, Gagnon, et. al. for the Society of Obstetricians and Gynaecologists of Canada (SOGC). Cancer Chemotherapy and Pregnancy. JOGC, 288: 263 -78; 2013. CAN 5. Perspective on a modified developmental and reproductive toxicity testing strategy for cancer immunotherapy. Int J Toxicol 2016 [epub] 6. CCOPE Database www. motherisk. org