[Clinical Pharmacology Research for Promoting Individualized Cancer Chemotherapy]

Yakugaku Zasshi. 2019;139(6):901-909. doi: 10.1248/yakushi.18-00213-1.
[Article in Japanese]

Abstract

Cancer chemotherapy has progressed remarkably with conventional and molecular-targeted anticancer drugs as well as immune checkpoint inhibitors. However, adverse drug reaction (ADR) management remains a challenge in cancer chemotherapy. Therefore, improving the quality of medical care through clinical pharmacology research is warranted. Intravenous injection of bendamustine in patients with follicular or mantle cell lymphoma frequently causes venous irritation. Because the underlying mechanisms are not clear, we investigated the factors responsible for bendamustine-induced venous irritation. Based on the results of our analysis, we altered the administration regimen and observed that the incidence of venous irritation, which manifested in a concentration-dependent manner following conventional approaches, significantly decreased when following the modified regimen. Guidelines on the management of chemotherapy-induced nausea and vomiting recommend aprepitant, a selective neurokinin-1 (NK-1) receptor antagonist, 5-hydroxytryptamine 3 (5-HT3) receptor antagonists, and dexamethasone as prophylactic antiemetics. Pretreatment with high-dose chemotherapy before hematopoietic stem cell transplantation has extremely high emetogenic potential. This can be countered by using aprepitant in combination with conventional antiemetics. However, the safety and efficacy of such combinations are unexplored. Upon evaluation, we observed improved antiemetic effects without an increase in ADRs. At this symposium, I highlight the significance of clinical pharmacology research for promoting individualized cancer chemotherapy.

Keywords: aprepitant; bendamustine; chemotherapy-induced nausea and vomiting; clinical pharmacology research; venous irritation.

Publication types

  • Review

MeSH terms

  • Antiemetics / administration & dosage
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects*
  • Aprepitant / administration & dosage
  • Bendamustine Hydrochloride / administration & dosage
  • Bendamustine Hydrochloride / adverse effects
  • Dose-Response Relationship, Drug
  • Humans
  • Injections, Intravenous
  • Nausea / chemically induced
  • Nausea / prevention & control
  • Neoplasms / drug therapy*
  • Pharmacology, Clinical*
  • Precision Medicine*
  • Quality of Health Care
  • Research*

Substances

  • Antiemetics
  • Antineoplastic Agents
  • Aprepitant
  • Bendamustine Hydrochloride