Every-other-day palonosetron plus aprepitant for prevention of emesis following induction chemotherapy for acute myeloid leukemia: A randomized, controlled study from the “Rete Ematologica Pugliese”

Nicola Di Renzo, Lorella Melillo, Fernando Porretto, Michela Dargenio, Vincenzo Pavone, Domenico Pastore, Patrizio Mazza, Donato Mannina, Anxur Merenda, Nicola Cascavilla, Giuseppina Greco, Rosella Matera, Erminio Bonizzoni, Luigi Celio, Maurizio Musso

Research output: Contribution to journalArticle

Abstract

Background: Compared with older 5-HT3 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 languageEnglish
JournalCancer Medicine
DOIs
Publication statusAccepted/In press - Jan 1 2019

Fingerprint

aprepitant
Induction Chemotherapy
Acute Myeloid Leukemia
Vomiting
Drug Therapy
Nausea
Treatment Failure
Serotonin 5-HT3 Receptor Antagonists
palonosetron
Receptors, Serotonin, 5-HT3
Antiemetics
Anthracyclines
Cytarabine

Keywords

  • acute myeloid leukemia
  • AML
  • aprepitant
  • CINV
  • emesis
  • nausea
  • palonosetron

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Every-other-day palonosetron plus aprepitant for prevention of emesis following induction chemotherapy for acute myeloid leukemia : A randomized, controlled study from the “Rete Ematologica Pugliese”. / Di Renzo, Nicola; Melillo, Lorella; Porretto, Fernando; Dargenio, Michela; Pavone, Vincenzo; Pastore, Domenico; Mazza, Patrizio; Mannina, Donato; Merenda, Anxur; Cascavilla, Nicola; Greco, Giuseppina; Matera, Rosella; Bonizzoni, Erminio; Celio, Luigi; Musso, Maurizio.

In: Cancer Medicine, 01.01.2019.

Research output: Contribution to journalArticle

Di Renzo, Nicola ; Melillo, Lorella ; Porretto, Fernando ; Dargenio, Michela ; Pavone, Vincenzo ; Pastore, Domenico ; Mazza, Patrizio ; Mannina, Donato ; Merenda, Anxur ; Cascavilla, Nicola ; Greco, Giuseppina ; Matera, Rosella ; Bonizzoni, Erminio ; Celio, Luigi ; Musso, Maurizio. / Every-other-day palonosetron plus aprepitant for prevention of emesis following induction chemotherapy for acute myeloid leukemia : A randomized, controlled study from the “Rete Ematologica Pugliese”. In: Cancer Medicine. 2019.
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abstract = "Background: Compared with older 5-HT3 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.",
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author = "{Di Renzo}, Nicola and Lorella Melillo and Fernando Porretto and Michela Dargenio and Vincenzo Pavone and Domenico Pastore and Patrizio Mazza and Donato Mannina and Anxur Merenda and Nicola Cascavilla and Giuseppina Greco and Rosella Matera and Erminio Bonizzoni and Luigi Celio and Maurizio Musso",
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T1 - Every-other-day palonosetron plus aprepitant for prevention of emesis following induction chemotherapy for acute myeloid leukemia

T2 - A randomized, controlled study from the “Rete Ematologica Pugliese”

AU - Di Renzo, Nicola

AU - Melillo, Lorella

AU - Porretto, Fernando

AU - Dargenio, Michela

AU - Pavone, Vincenzo

AU - Pastore, Domenico

AU - Mazza, Patrizio

AU - Mannina, Donato

AU - Merenda, Anxur

AU - Cascavilla, Nicola

AU - Greco, Giuseppina

AU - Matera, Rosella

AU - Bonizzoni, Erminio

AU - Celio, Luigi

AU - Musso, Maurizio

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: Compared with older 5-HT3 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.

AB - Background: Compared with older 5-HT3 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.

KW - acute myeloid leukemia

KW - AML

KW - aprepitant

KW - CINV

KW - emesis

KW - nausea

KW - palonosetron

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