53 3 CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING | PART TWO Background Delayed CINV, defined as nausea and vomiting occurring more than 24 hours after completion of chemotherapy, remains an important and common adverse event complicating cancer treatment. Delayed CINV significantly interferes with patient’s quality of life and daily functioning [1,2]. Incidence and severity of CINV are affected by patient and treatment related factors. Characteristics associated with a higher risk include female sex, anxiety, and poor control with previous chemotherapy [3,4]. Delayed CINV is influenced by the effectiveness of control of the acute phase of CINV, as well as the intrinsic emetogenicity of the drug. The risk of delayed CINV has been studied best in chemotherapy regimens containing high-dose cisplatin or anthracyclines and cyclophosphamide (AC) combinations. However, delayed CINV is also associated with moderately emetogenic chemotherapy regimens (non-AC MEC) [5-10]. Non-AC MEC consists of a broad range of chemotherapeutic agents, with emetogenic potentials of 30% to 90%; agents like oxaliplatin and irinotecan have an emetogenic potential in the lower part of this range, as opposed to carboplatin, which is at the high end [11,12]. In 2013, the Multinational Association for Supportive Care in Cancer (MASCC) and the European Society of Medical Oncology (ESMO) last updated their guidelines for the management of CINV in adults [13]. In 2011, the American Society of Clinical Oncology (ASCO) published the last updated clinical practice guideline for antiemetics in oncology [14]. All guidelines recommend palonosetron combined with dexamethasone for the prevention of acute CINV following non-AC MEC, with multiday oral dexamethasone as the preferred treatment for the prevention of delayed CINV (level of evidence IIb). These recommendations are based however on phase III trials, which did not evaluate the combination of palonosetron and dexamethasone in MEC, but only in HEC and AC chemotherapy [15,16]. Also, patients in the aforementioned trials did not receive optimal antiemetic treatment with NK1 receptor antagonists, as recommended for HEC and AC chemotherapy, which may have influenced the results. Despite the recommended combination of palonosetron andmultiday dexamethasone, many patients still experience delayed CINV following non-AC MEC. In a small observational trial with colorectal cancer patients, palonosetron and dexamethasone failed to provide both complete response (CR) and complete control (CC) in 15% of the patients in the delayed phase [17]. In another phase III trial with palonosetron and dexamethasone administered for 3 days, almost 25% of the patients did not achieve CR in the delayed phase. [18]. Further evidence on the efficacy of new strategies to prevent delayed CINV after non-AC MEC is therefore needed. This systematic review aims to provide a comprehensive assessment of recently performed RCTs on this specific topic.
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