Abstract
BACKGROUND: Compared with older 5-HT(3) receptor antagonists, palonosetron requires fewer drug administrations to prevent chemotherapy-induced nausea and vomiting (CINV) following multiple-day chemotherapy. We conducted a phase II multicenter study comparing palonosetron plus aprepitant to palonosetron alone in patients undergoing a range of induction chemotherapy regimens for acute myeloid leukemia (AML). METHODS: Patients were randomized to palonosetron (0.25 mg) every other day until the last dose of chemotherapy alone or with aprepitant on days 1-3. Patients mainly received an anthracycline on days 1-3 plus cytarabine administered for 5-10 days. The primary end point was complete response (CR; no emesis and no rescue medication) over the whole study period (days of chemotherapy plus two additional days). Unplanned analysis of time to anti-emetic treatment failure (TTF) was also performed. RESULTS: Of the 134 patients enrolled in the study, 130 were evaluable: 68 subjects received palonosetron plus aprepitant and 62 received palonosetron alone. Although the primary end point of CR was similar between the treatment arms (72% vs 69%; P = .55), a higher proportion of patients treated with palonosetron plus aprepitant were free from nausea during the whole study period (43% vs 27%; P = .03). There was also a significant difference in favor of the two-drug regimens in TTF (median: 5 days vs 3 days; P = .03). CONCLUSIONS: The study suggests that every-other-day palonosetron plus 3-day aprepitant can add clinical benefit to the control of CINV caused by multiple-day, corticosteroid-free chemotherapy for AML. In this challenging setting of CINV, further investigations of palonosetron in combination with aprepitant administered with an expanded schedule are warranted. ClinicalTrial.gov identifier: NCT02205164.
Original language | English |
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Pages (from-to) | 170-178 |
Number of pages | 9 |
Journal | Cancer Med. |
Volume | 9 |
Issue number | 1 |
DOIs | |
Publication status | Published - 2020 |
Keywords
- Adult
- Female
- Humans
- Male
- Middle Aged
- Aged
- Young Adult
- Aged, 80 and over
- Drug Administration Schedule
- Treatment Failure
- *acute myeloid leukemia
- *AML
- *aprepitant
- *CINV
- *emesis
- *nausea
- *palonosetron
- Anthracyclines/administration & dosage/adverse effects
- Antiemetics/*administration & dosage
- Antineoplastic Combined Chemotherapy Protocols/administration & dosage/*adverse effects
- Aprepitant/administration & dosage
- Cytarabine/administration & dosage/adverse effects
- Drug Therapy, Combination/methods
- Induction Chemotherapy/adverse effects/methods
- Leukemia, Myeloid, Acute/*drug therapy
- Nausea/chemically induced/*epidemiology/prevention & control
- Palonosetron/administration & dosage
- Vomiting/chemically induced/*epidemiology/prevention & control