Pathophysiology, Severity, Pattern, and Risk Factors for Carboplatin-induced Emesis

Abstract

Carboplatin has proven efficacy in the treatment of ovarian cancer and has been proven to be less toxic compared to the parent compound cisplatin. Nevertheless, emesis is still a major problem associated with carboplatin-containing chemotherapy. Several investigators have focussed on the understanding of the pathophysiology and pattern of cisplatin-induced emesis. Data describing both the pathomechanisms and pattern of carboplatin-induced emesis are still lacking. This paper combines data from the literature with our own experience with the pattern and control of carboplatin-induced emesis, and presents data contributing to the understanding of the underlying pathomechanisms. Carboplatin induces a significant increase in urinary 5-HIAA excretion, the main metabolite of serotonin. 5-HIAA excretion levels remain elevated over 3 days following chemotherapy. Carboplatin-induced emesis is observed in about 40% of patients despite anti-emetic prophylaxis with 5-HT₃ antagonists. Vomiting after carboplatin extends over days 1–3 with an equal distribution regarding the severity on each day. Analysis of the pattern of emesis revealed that delayed emesis ( > 24 h after chemotherapy) is a major problem associated with carboplatin therapy. Description of the pattern of emesis as ‘prolonged emesis’ seems to be appropriate. 5-HT₃ receptor antagonists such as ondansetron seem to be efficacious both in the control of acute and prolonged emesis following carboplatin chemotherapy, but randomly controlled data comparing ondansetron with other anti-emetic regimens have not yet been published. Univariate analysis reveals gender and combination therapy containing carboplatin and cyclophosphamide and/or anthracyclines as risk factors for emesis.

5-HT₃-Receptor Antagonists in the Management of Nausea and Vomiting in Cancer and Cancer Treatment

“…Delayed emesis starts at least 24 h after cancer therapy and may last for more than 5 days, with a peak incidence at around day 2–3 depending upon the agent [89,90,91,92] (fig. 3).…”

“…3). Delayed emesis is reported to occur in up to 93% of patients receiving cisplatin-based chemotherapy [89] and in a substantial proportion of those receiving cyclophosphamide or carboplatin [91, 92]. …”

Antiemetic efficacy of the neurokinin‐1 antagonist, aprepitant, plus a 5HT3 antagonist and a corticosteroid in patients receiving anthracyclines or cyclophosphamide in addition to high‐dose cisplatin

“…The development of classification systems for emetogenicity illustrates the importance of this feature of antineoplastic drugs in planning supportive care. 2,16 Furthermore, the mechanism of emetogenic action varies among different chemotherapeutic drugs, 17,18 suggesting a need for more than one class of antiemetic therapy to correspond with the different emetic stimuli potentially produced by a multidrug chemotherapy regimen. 19 Even a single drug may have an emetogenic potential of complex origin.…”

Paclitaxel, Carboplatin, and Trastuzumab

“…3,9 Although carboplatin is reported to cause delayed nausea or emesis similar to cisplatin, the mechanism of action and clinical course of carboplatin-induced nausea and vomiting differ from cisplatin. 31,32 Analysis of urinary 5-hydroxyindole acetic acid (5-HIAA) excretion indicates that carboplatin causes a lower peak level, but more prolonged release, of serotonin than cisplatin. The clinical course of carboplatin-induced emesis refl ects this pattern of serotonin release.…”