Assessment of safety and tolerability of subcutaneous trastuzumab in patients with HER2-positive early breast cancer: Results of an open-label, randomized, multicenter, phase IIIB ESCAPE trial.

Aim: To assess the safety and tolerability of subcutaneous (SC) trastuzumab (Herceptin) administered either with a single-use injection device (SID) or manually from a vial using a hand-held syringe.

Methods: The ESCAPE trial (NCT02194166) included 90 women aged 18 years or older with HER2-positive early breast cancer who underwent surgical treatment and completed (neo) adjuvant chemotherapy and radiotherapy (if indicated). Patients enrolled in the study were first subjected to 4 cycles of trastuzumab IV (8 mg/kg loading dose followed by 6 mg/kg maintenance dose, q3w) prior to being randomized into groups: [A] SC trastuzumab (fixed dose 600 mg, q3w) administered through a hand-held syringe followed by 7 cycles of SC trastuzumab administered with an SID or [B] the reverse sequence.

P-glycoprotein substrates and antagonists cluster into two distinct groups.

To gather further insight into the interaction between P-glycoprotein (Pgp) and its substrates, 167 compounds were analyzed in multidrug resistant human colon carcinoma cells. These compounds were selected from the National Cancer Institute Drug Screen repository using computer-generated correlations with known Pgp substrates and antagonists. The compounds were prospectively defined as Pgp substrates if cytotoxicity was increased > or =4-fold by the addition of cyclosporin A (CsA) and as Pgp antagonists if inhibition of efflux increased rhodamine accumulation by 4-fold.