No abstract

No abstract

Purpose: Ertumaxomab is an intact bispecific antibody targeting HER2/neu and CD3 with selective binding to activatory Fcγ type I/III receptors, resulting in the formation of a tri-cell complex between tumor cells, T cells, and accessory cells. Patients with metastatic breast cancer were enrolled into a multicenter phase I dose-escalating trial. Experimental Design: Three ascending doses of ertumaxomab (10-200 μg) were administered i.v. on day 1, 7 ± 1, and 13 ± 1. Safety and tolerability were the primary objectives. Secondary objectives were antitumor activity and different immunologic variables. Results: Fifteen out of 17 enrolled patients completed the study. One hundred micrograms was identified as the maximal tolerable single dose. Most drug-related adverse events were mild and transient including fever (94%), rigors (47%), headache (35%), nausea (29%), vomiting (29%). Grades 3 and 4 (Common Toxicity Criteria) were lymphocytopenia (76%) and elevation of liver enzymes (47%). One patient (200 μg dose) developed severe hypotension and respiratory distress syndrome, another patient (150 μg dose) developed a systemic inflammatory response syndrome and acute renal failure. Aggravation of congestive heart failure was seen in one patient with preexisting ventricular dysfunction after administration of the third dose (200 μg). All adverse events were fully reversible. Antitumor response was seen in 5 out of 15 evaluable patients (one with a complete response, two with partial responses, two with stable disease) at dose levels of ≥100 μg. Measurements of cytokines (interleukin-6, interleukin-2, tumor necrosis factor-α, and IFN-γ) suggest a strong T helper cell type 1–associated immune response. The induction of human anti-mouse/anti-rat antibodies was detected in 5 out of 16 (31%) patients. Discussion: Treatment with triple infusions of ertumaxomab yields a strong immunologic response. Doses up to 100 μg can be safely infused with close monitoring of patients. The observed clinical responses are encouraging and indicate antitumor efficacy.

No abstract

Background: To increase the evidence for treatment of breast cancer during pregnancy, the German Breast Group launched a registry (GBG-29/BIG 02-03) for patients with breast cancer diagnosed during pregnancy. Patients: Every pregnant breast cancer patient was eligible. The primary endpoint is the fetal outcome 4 weeks after delivery. Secondary endpoints were maternal outcome of pregnancy, stage and biological characteristics of breast cancer, breast cancer therapy (treatment, response to chemotherapy, type of surgery, outcome of the mother and newborn after 5 years. Results: From April 2003-June 2010, 313 patients have been prospectively (n=185) and retrospectively (n=128) registered. 24 pts were registered without clinical data and were removed from the data set. The median age was 33 years (range 23-47). T1-2: 71%; T3-4: 25%; inflammatory 4%, N+ 48%; ductal invasive/other 97%, grade 3: 64%, HR+/HER2- 26%; HR+/HER2+ 22%; HR-/HER2- 34%; HR-/HER2+ 18%. At the time of diagnosis the median gestational age was 23 weeks; 23% of all patients were diagnosed during the 1st, 42% during the 2nd and 36% during the 3rd trimester. 29 pts (10%) had an abortion. 260 continued pregnancy. 142/260 (54%) patients received 527 chemotherapy (CHT) cycles (c) during pregnancy with a median of 4 cycles per pt (1 n=8; 2 n=25; 3n=23; 4 n=52; 5 n=14; 6n=19; 8 n=1). CHT regimen used during pregnancy are: EC/AC n=70, FE(A)C n=29; Vincaalcaloids/A n=12; A/E mono n=10; CMF n=14, taxanes n=6. 48% had a caesarean section. Mean weight of the newborns after intrauterine CHT was 2810g (1270-4050g) delivered at median 37 weeks (range 31-42) compared with newborns not exposed to CHT with 2730g (1260-4295g) delivered at median 38 weeks (range 30-42 weeks). Patients w/o CHT during pregnancy had a significantly higher rate of premature deliveries compared with those with CHT (33% vs 17%; p=0.009). Of the 142 babies exposed to CHT adverse events are: 4 infections, 4 congenital malformations, 1 small for gestational age, 1 CPAP, 1 hyperbilirubinemia, 1 neutropenia, and 2 anemia; 1 thalassemia,1 trisomia 18 (died one week after birth), 1 necrotic enterocolitis (died 3 weeks after birth). The group w/o CHT during pregnancy reported temporary apnea; CPAP, hypoglycemia, congenital malformation, icterus, neutropenia (1 each). Overall median DFS of the mothers was 27 (95% CI 22-32) months. OS was 55 (95% CI 32-79) months. Significant differences in DFS were found between DFS in pts w/o CHT during pregnancy, pts with CHT during pregnancy, and pts with an abortion (29 vs 25 vs 15 months; log rank p=0.0372). Conclusion: Premature deliveries were significantly more common within the group of pts not receiving CHT during pregnancy probably to allow for an early start of CHT. However, fetal outcome in babies, who received intrauterine chemotherapy was not significantly different from those who did not if matched to gestational age. Pregnant breast cancer pts should be treated as closely as possible to standard recommendations. Early delivery with the risk of prematurity of the newborns is unnecessary and an abortion might even have a negative effect on the outcome. Supported by the BANSS Foundation Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S6-2.