71 4 CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING | PART TWO this study, three antiemetic regimens for prevention of delayed CINV were compared: ondansetron 8 mg IV and DEX 8 mg IV on day 1 with DEX 4 mg orally (PO) twice daily on days 2-3 (DEX arm); ondansetron 8 mg IV and DEX 8 mg IV on day 1 with metoclopramide 10 mg PO three times daily on days 2-3 (MCP arm); palonosetron 0.25 mg IV and DEX 8 mg IV on day 1 with no additional doses of antiemetics (PAL arm). Dose, dosage, and route of administration of antiemetic treatment were according to current clinical guidelines (supplemental Table S1). Ondansetron, metoclopramide, DEX, and benzodiazepines were permitted as rescue antiemetics during chemotherapy treatment. During days 1–5 (0-120 hr), each patient completed a diary, capturing emetic episodes, severity of nausea and intake of rescue antiemetics. An emetic episode was defined as any episode of vomiting or retching, or combined vomiting and retching. Severity of nausea was evaluated using a 7-point Likert scale, ranging from no nausea (0 points) to nausea as bad it could be (7 points). On day 2, a telephone call was made by study personnel to ensure adherence to the required documentation and the prescribed study medication at home. On day 8, diaries were collected and reviewed. The proportions of patients with scores reflecting no vomiting, no nausea (score 0 on the Likert scale), no significant nausea (score ≤2 on the Likert scale), and no intake of rescue antiemetics were evaluated. The validated modified version of the Functional Living Index-Emesis (FLIE) questionnaire with a 5-day recall period was used to assess the impact of acute and delayed CINV on patients’ daily lives (24). The FLIE questionnaire (consisting of nine nausea-specific and nine vomiting-specific items) was completed by patients on days 2 and 6 post-chemotherapy. Responses were marked on a 100 mm VAS with anchors of 1 and 7. The proportion of patients with scores reflecting ‘no or minimal impact on daily life’ (NIDL), defined as total FLIE score >108, was evaluated. The Dexamethasone Symptom Questionnaire (DSQ), a self-report questionnaire designed to be completed one week after the initiation of MEC, was used to rate the incidence and severity of DEX-associated side effects (17). The DSQ includes eight items evaluating insomnia, gastroesophageal reflux, increased appetite, rash/acne, hiccups, oral candida, agitation, and feelings of depressing on ceasing medication. Responses were formatted using a four-point Likert scale (1 = not at all, 2 = a little bit, 3 = quite a bit, 4 = very much). The proportion of patients with moderate to severe side effects (score 3 or 4) was evaluated. The clinician-rated Abnormal Involuntary Movement Scale (AIMS) was used on day 8 to assess the severity of metoclopramide-associated dyskinesias (25). The AIMS consists of four categories: facial and oral movements (four items), extremity movements (two items), trunk movements (one item), global judgment (three items); each item being scored from 0 to 4 (i.e. none = 0 points, minimal = 1 point, mild = 2 points, moderate = 3 points, severe = 4 points). The proportion of patients with mild to severe dyskinesias (scores ≥2) was evaluated. The primary efficacy endpoint was total control (TC; defined as no emetic episodes, no use of rescue medication, and no nausea) in the delayed phase. Secondary efficacy endpoints included TC rates during the acute and overall (0-120 hr post-chemotherapy) phases, no vomiting, no significant nausea, no nausea, no use of rescue antiemetics, complete response (CR; defined as no emetic episodes, no use of rescue medication), and complete protection (CP; defined as no emetic episodes, no use of rescue medication, no significant nausea) during all phases. Mean FLIE scores and FLIE scores reflecting NIDL during the
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