Abstract and Introduction
Review the clinical evidence of tropisetron or palonosetron, an old- and new-generation serotonin (5-hydroxytryptamine) type 3 (5-HT3) receptor antagonist (RA), respectively, for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients with cancer, and evaluate any difference in efficacy trends. A literature search of the EMBASE and PubMed databases was performed to identify publications of intravenous (IV) tropisetron (generic forms or Navoban®) for the treatment of CINV in patients with various cancers. Data from the pivotal clinical studies evaluating the IV formulation of Aloxi® (palonosetron HCl) were also considered. The effectiveness and safety of each antiemetic was summarized. Sixteen papers for tropisetron fulfilled the inclusion criteria and were extracted for full analysis; publications from six pivotal palonosetron clinical trials were considered. No direct data comparisons could be made between the two drugs, due to the varying definitions of efficacy endpoints between studies. For tropisetron, the rates of no emesis were lower in patients receiving highly emetogenic chemotherapy (HEC) versus moderately emetogenic chemotherapy (MEC). For palonosetron, the rates of complete response (no emesis, no rescue medication) were comparable in the MEC and HEC settings, demonstrating the effectiveness of this agent in patients receiving HEC. Both antiemetics offered some protection against nausea, although lower rates of no nausea were achieved compared with rates of no emesis. Two trials that evaluated the efficacy of palonosetron and tropisetron within the same study reported that palonosetron was more effective than tropisetron in controlling delayed vomiting in the HEC and MEC settings, with significantly higher rates of no emesis observed (P≤0.01). Palonosetron was non-inferior or more efficacious in controlling CINV compared with other older 5-HT3RAs, such as dolasetron, ondansetron, and granisetron. Conversely, tropisetron was no more efficacious than ondansetron or granisetron. Both tropisetron and palonosetron were generally well tolerated, with adverse event profiles consistent with drugs of this class (e.g., headache, constipation, and diarrhea). These data suggest that palonosetron is a highly selective prophylactic agent that may have an improved therapeutic profile compared with tropisetron, and is a feasible treatment option for controlling CINV in patients with cancer.
Chemotherapy-induced nausea and vomiting (CINV), a highly distressing and frequent complication in patients with cancer, can negatively impact quality of life and adherence to therapy,[2–5] and may be associated with considerable healthcare costs.
CINV is a complex and multifactorial process mediated by multiple neurotransmitters, including serotonin, substance P, and dopamine. Serotonin (5-hydroxytryptamine) type 3 (5-HT3) receptor antagonists (RAs) block 5-HT3 receptors involved in regulating nausea and vomiting in the acute (0–24 hours after chemotherapy) setting. Thought to act via the central nervous system and the vagus and splanchnic nerves in the gastrointestinal tract, 5-HT/5-HT3 receptor signaling may also influence delayed (24–120 hours after chemotherapy) nausea and vomiting, possibly by sensitizing the vagus nerve to chemicals such as substance P.[9–11]
5-HT3 RAs, which may be described as old and new generation, form the cornerstone of antiemetic regimens recommended by international guidelines.[12–14] Currently used older 5-HT3 RAs include azasetron; dolasetron, granisetron, and ondansetron; tropisetron; and ramosetron. At the recommended dose, these agents show similar efficacy and safety,[8,18–20] with cost being the main differentiator. Despite their effectiveness in controlling CINV in the acute phase, they are not as effective in the delayed phase,[21–23] prompting the development of a new 5-HT3 RA, palonosetron.
Both palonosetron and tropisetron are used as first-line agents to prevent CINV in China, although anecdotal evidence suggests that tropisetron may be favored, despite the lack of evidence to support its superior efficacy. Tropisetron, one of the first 5-HT3 RAs to be developed, has shown promising antiemetic properties in pilot studies,[25,26] with acute CINV control rates of approximately 70%. Palonosetron is a pharmacologically and clinically distinct new-generation 5-HT3 RA[27,28] that various meta-analyses have shown to be more effective than older 5-HT3 RAs.[29–32] It exhibits a higher binding affinity for 5-HT3 receptors and synergistically interacts with the neurokinin 1 (NK1) receptor signaling pathway,[27,33] which may partially account for palonosetron's effectiveness in the delayed phase. Palonosetron comes in two formulations, oral (0.50 mg) and intravenous (IV; 0.25 mg).
This review aimed to summarize the clinical data on tropisetron IV and Aloxi® (palonosetron HCl) IV, in the first-line setting in patients with CINV, and evaluate the 5-HT3 RA benefit to patients in terms of preventing nausea and/or vomiting.
Chin Clin Oncol. 2020;9(2):17 © 2020 AME Publishing Company