Efficacy and safety of 5HT3RA, DEX, and NK1RA for the prevention of FOLFIRINOX-induced nausea and vomiting in patients with pancreatic cancer: a retrospective cohort study

Support Care Cancer. 2023 Oct 26;31(12):657. doi: 10.1007/s00520-023-08136-0.

Abstract

Purpose: Modified FOLFIRINOX (mFFX), a standard chemotherapy regimen for advanced pancreatic cancer (APC), is expected to be associated with a higher risk of chemotherapy-induced nausea and vomiting (CINV). Herein, we conducted a retrospective cohort study to evaluate the efficacy and safety of a three-drug combination of 5-hydroxytryptamine-3 receptor antagonists (5HT3RA), dexamethasone (DEX), and neurokinin 1 receptor antagonists (NK1RA) for the prevention of CINV during mFFX therapy.

Methods: This study enrolled patients with APC who received mFFX as initial therapy with a combination of 5HT3RA, DEX, and NK1RA as antiemetic prophylaxis. The primary endpoint was the complete response (CR) rate during cycle 1, which was defined as no emetic episodes and no rescue medication use during the overall period (0-120 h). Safety was also evaluated with a focus on hyperglycemia, which is a concern in patients with APC.

Results: Seventy patients were eligible for this retrospective analysis. The CR rate during the overall period was 51.4%. Significant nausea, defined as grade 2 or higher, peaked to 77.1% on days 4-5, but remained above 65% until day 7. Hyperglycemia occurred in 37.1% of patients, and 34.3% were grade 3 hyperglycemia.

Conclusions: CINV induced by mFFX was poorly controlled even with prophylactic antiemetic therapy using 5HT3RA, DEX, and NK1RA, and was found to persist beyond 5 days. Enhanced antiemetic measures for mFFX are desirable. However, in patients with diabetes mellitus complications, sparing of steroids and glycemic control should be considered.

Keywords: Advanced pancreatic cancer; Antiemetic therapy; Chemotherapy; Chemotherapy-induced nausea and vomiting.

MeSH terms

  • Antiemetics* / therapeutic use
  • Antineoplastic Agents* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Dexamethasone / therapeutic use
  • Humans
  • Hyperglycemia*
  • Nausea / chemically induced
  • Nausea / drug therapy
  • Nausea / prevention & control
  • Neurokinin-1 Receptor Antagonists / therapeutic use
  • Pancreatic Neoplasms* / drug therapy
  • Retrospective Studies
  • Vomiting / chemically induced
  • Vomiting / drug therapy
  • Vomiting / prevention & control

Substances

  • Antiemetics
  • Neurokinin-1 Receptor Antagonists
  • folfirinox
  • Dexamethasone
  • Antineoplastic Agents