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Whereas the effects of chemotherapy during pregnancy for mother and fetus are well described, its effects on the placenta remain largely undetermined. We performed a retrospective clinicopathologic analysis of the placenta following chemotherapy. Charts were reviewed for type of malignancy, type and timing of chemotherapy, and fetal and pregnancy outcome. Placentas were studied by standard pathologic analysis as well as computer-assisted morphometry and fluorescence in situ hybridization (FISH) analysis. Patients (n = 13) underwent chemotherapy during pregnancy for carcinoma of breast (3), ovary (2), cervix (2), salivary gland (1), lymphoma/leukemia (4), or rhabdomyosarcoma (1). Eleven patients were treated with DNA-active cytotoxic agents during the 2nd and/or 3rd trimesters; their placentas showed nonspecific findings, including villous hypermaturity, distal villous hypoplasia, villous edema, and excessive extravillous trophoblast, and 4/11 (36%) were small-for-age. In one case (rhabdomyosarcoma), the mother was exposed to cytotoxic agents throughout the entire pregnancy. In this case, associated with severe congenital anomalies, the placenta showed striking nuclear pleomorphism of the extravillous trophoblast of the chorion laeve, associated with FISH-demonstrated hyperpolyploidy. One patient was treated with the targeted tyrosine kinase inhibitor, imatinib, in 2 consecutive pregnancies; these placentas showed no specific anomalies. Our findings suggest that chemotherapy during the 1st trimester induces excessive polyploidization of the chorion laeve trophoblast, likely representing an adaptive response to intraamniotic toxins. Second and 3rd trimester exposure to cytotoxic agents may predispose to placental underdevelopment. However, without appropriate controls (untreated patients with equivalent malignancies), the specific effects of chemotherapy in this group are difficult to assess.

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Female BALB/c mice were infected with coxsackievirus B3 in the diestrus, proestrus, estrus, or metestrus phases of the ovarian cycle. Cycle stage was determined by vaginal smear. All mice were killed 7 days after infection. Females infected in the diestrus and especially the proestrus phases developed myocarditis. CD4+ T cells expressing interferon-gamma (IFNgamma) infiltrate the myocardium in these two phases, whereas CD4+ T cells expressing IL-4 are more frequent during estrus. Cardiac virus titers were determined 15 h and 7 days after infection. No differences in virus titer were seen at 7 days. These studies show that natural hormone variations can have substantial effects on viral pathogenicity presumably due to hormone effects on the immune system.

Purpose Bone pain is a common side-effect of pegfilgrastim and can interfere with quality of life and treatment adherence. This study i nvestigated the impact of antihistamine prophylaxis on pegfilgrastim-induced bone pain. Methods This is a two stage enrichment trial design. Patients receiving an initial dose of pegfilgrastim after chemotherapy were enrolled into the observation stage (OBS). Those who developed significant back or leg bone pain (SP) were enrolled into the treatment stage (TRT) and randomized to daily loratadine 10 mg or placebo for 7 days. SP was defined by Brief Pain Inventory as back or leg pain score ≥ 5 and a 2 point increase after pegfilgrastim. The primary end-point of TRT was reduction of worst back or leg bone pain with loratadine, defined as 2 point decrease after treatment compared to OBS. Results 213 patients were included in the final analysis. Incidence of SP was 30.5%. The SP subset had a worse overall Functional Assessment of Cancer Therapy – Bone Pain score (33.9 vs. 51.7, p < 0.001) and a higher mean white blood cell count (15.4 vs. 8.4 K/cm3, p = 0.013) following pegfilgrastim than those without SP. 46 patients were randomized in the TRT. Benefit was 77.3% with loratadine and 62.5% with placebo (p = 0.35). Baseline NSAID use was documented in 4 patients (18.2%) in loratadine arm and 2 patients (8.3%) in placebo arm, with baseline non-NSAID use documented in 5 (22.7%) and 6 (25%) patients respectively. Eight additional patients used NSAIDS by day 8 compared to day 1 (6 in the loratadine and 2 in the placebo arm). A total of 6 additional patients used non-NSAIDS by day 8 compared to day 1 (4 in the loratadine and 2 in the placebo arm). Conclusions Administration of prophylactic loratadine does not decrease the incidence of severe bone pain or improve quality of life in a high-risk patient population.

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Erlotinib is the standard of care for epidermal growth factor receptor (EGFR) mutated lung adenocarcinomas in the United States. However, in pregnant patients with lung cancer, chemotherapy is recommended, irrespective of EGFR mutations, given the lack of experience and uncertainty for fetus's safety with erlotinib.