Phase I and pharmacological trial of lapatinib in combination with gemcitabine in patients with advanced breast cancer.

BACKGROUND: Lapatinib has proven efficacy as monotherapy and in combination with capecitabine in patients with metastatic breast cancer (MBC) overexpressing HER2 and/or EGFR. Gemcitabine also has anti-tumor activity in MBC and a favourable toxicity profile. In this phase I study lapatinib and gemcitabine were combined. METHODS: Female patients with advanced BC were given lapatinib once daily (QD) in 28-day cycles with gemcitabine administered on day 1, 8 and 15. Physical examinations, vital signs and blood sampling for hematology, clinical chemistry and pharmacokinetics (PK) and radiological assessments of disease were performed at regular intervals. RESULTS: In total, 33 patients were included. Six dose-limiting toxicities were observed, mostly grade 3 increases in liver function tests. Most common toxicities were fatigue (73%), nausea (70%), diarrhea (58%), increases in ALAT and ASAT (55 and 52%, respectively) and rash (46%). The maximum tolerated dose was lapatinib 1250 mg QD with gemcitabine 1000 mg/m(2). Lapatinib and gemcitabine PK did not appear to be influenced by each other. Anti-tumor activity was observed with one patient (4%) showing complete response and six (23%) partial response. CONCLUSION: Despite a slightly increased toxicity profile compared to their respective monotherapies, lapatinib and gemcitabine can be safely combined while showing signs of anti-tumor activity.

Citalopram serum and milk levels in mother and infant during lactation.

We present a case of intensified therapeutic drug monitoring (TDM) of citalopram in mother and newborn infant after clinically observed selective serotonin reuptake inhibitor (SSRI)-associated symptoms 2 weeks until 2 months after delivery. The SSRI-associated symptoms observed in the infant (up to 3 weeks after delivery) were irregular breathing, sleep disorders, hypotonia, and hypertonia. We conclude that the SSRI-associated symptoms in the infant represent citalopram withdrawal effects rather than side effects caused by breastfeeding. This case illustrates the importance of a flexible TDM program and a multidisciplinary approach in a hospital setting to deal with cases of drug-associated adverse effects, such as SSRI withdrawal effects.

[Diagnostic image (239). A male newborn with a skin lesion on a knee]. / Diagnose in beeld (239). Een pasgeboren jongen met een huidafwijking aan de knie.

Cutis marmorata teleangiectatica congenita was diagnosed in a male neonate.

Enlarged nuchal translucency and low serum protein concentrations as possible markers for Zellweger syndrome.

We present a case of a fetus in which an enlarged nuchal translucency was detected at 12 weeks' gestation. The karyotype was normal. Subsequent ultrasound examination showed no obvious fetal abnormalities apart from a mild pericardial effusion. Serum screening revealed very low concentrations of estriol and human chorionic gonadotropin. After birth the diagnosis of Zellweger syndrome was made. Nuchal translucency screening, estriol level identification and detailed ultrasound scanning may help to identify fetuses affected by this syndrome.