Prolonged Administration of Aprepitant Does Not Increase Toxicity in Patients Undergoing High Dose Chemotherapy and Autologous Stem Cell Transplant.

Aprepitant is a neurokinin-1 receptor antagonist used for the prevention of chemotherapy induced nausea and vomiting (CINV) with highly emetogenic chemotherapy. The recommended dose for the prevention of CINV is 125 mg orally on day of treatment, followed by 80 mg orally on days 2 and 3. It is known that aprepitant inhibits cytochrome P450 3A4, therefore elevating plasma concentrations of various drugs, including certain chemotherapy drugs such as etoposide. Given the highly emetogenic nature and length of conditioning regimens used in Bone Marrow Transplant (BMT) patients, we elected to treat patients for a longer period of time with aprepitant. Twenty-five patients received aprepitant for an average of 7.6 days, with an initial dose of 125 mg p.o. on day 1 and 80 mg p.o. on subsequent days. Eleven patients were women and the remaining fourteen were men. The youngest transplanted patient was 20 and the oldest was 68 years old. Engraftment was defined as

1. an absolute neutrophil count (ANC) greater than 1000 x 3 days and

2. number of days until platelet transfusion independence.

The mean day to ANC recovery was 12.3 and the mean day of platelet transfusion independence was 13. This data was based on 24 patients, as one male patient died day +10 secondary to RSV bronchiolitis prior to engraftment. The incidence of mucositis, neutropenic fevers, pulmonary toxicities, and other complications did not differ compared with previously established data. We conclude that aprepitant can be used safely without adding significant toxicity to therapy with high dose chemotherapy in autologous stem cell transplant patients. A randomized prospective trial should be considered to evaluate the efficacy in reducing CINV and to further evaluate toxicity.