TY - JOUR
T1 - Phase i and pharmacokinetic study of romidepsin in patients with cancer and hepatic dysfunction
T2 - A national cancer institute organ dysfunction working group study
AU - ETCTN-9008 Study Team
AU - Connolly, Roisin M.
AU - Laille, Eric
AU - Vaishampayan, Ulka
AU - Chung, Vincent
AU - Kelly, Karen
AU - Dowlati, Afshin
AU - Alese, Olatunji B.
AU - Harvey, R. Donald
AU - Haluska, Paul
AU - Siu, Lillian L.
AU - Kummar, Shivaani
AU - Piekarz, Richard
AU - Ivy, S. Percy
AU - Anders, Nicole M.
AU - Downs, Melinda
AU - O'Connor, Ashley
AU - Scardina, Angela
AU - Saunders, Jacqueline
AU - Rosner, Gary L.
AU - Carducci, Michael A.
AU - Rudek, Michelle A.
N1 - Publisher Copyright:
© 2020 American Association for Cancer Research.
PY - 2020/10/15
Y1 - 2020/10/15
N2 - Purpose: Romidepsin dosing recommendations for patients with malignancy and varying degrees of hepatic dysfunction was lacking at the time of regulatory approval for T-cell lymphoma. We conducted a multicenter phase I clinical trial (ETCTN-9008) via the NCI Organ Dysfunction Working Group to investigate safety, first cycle MTD, and pharmacokinetic profile of romidepsin in this setting. Patients and Methods: Patients with select advanced solid tumors or hematologic malignancies were stratified according to hepatic function. Romidepsin was administered intravenously on days 1, 8, and 15 of a 28-day cycle and escalation followed a 3 þ 3 design in moderate and severe impairment cohorts. Blood samples for detailed pharmacokinetic analyses were collected after the first dose. Results: Thirty-one patients received one dose of romidepsin and were evaluable for pharmacokinetic analyses in normal (n ¼ 12), mild (n ¼ 8), moderate (n ¼ 5), and severe (n ¼ 6) cohorts. Adverse events across cohorts were similar, and dose-limiting toxicity occurred in two patients (mild and severe impairment cohorts). The MTD was not determined because the geometric mean AUC values of romidepsin in moderate (7 mg/m2) and severe (5 mg/m2) impairment cohort were 114% and 116% of the normal cohort (14 mg/m2). Conclusions: Data from the ETCTN-9008 trial led to changes in the romidepsin labeling to reflect starting dose adjustment for patients with cancer and moderate and severe hepatic impairment, with no adjustment for mild hepatic impairment.
AB - Purpose: Romidepsin dosing recommendations for patients with malignancy and varying degrees of hepatic dysfunction was lacking at the time of regulatory approval for T-cell lymphoma. We conducted a multicenter phase I clinical trial (ETCTN-9008) via the NCI Organ Dysfunction Working Group to investigate safety, first cycle MTD, and pharmacokinetic profile of romidepsin in this setting. Patients and Methods: Patients with select advanced solid tumors or hematologic malignancies were stratified according to hepatic function. Romidepsin was administered intravenously on days 1, 8, and 15 of a 28-day cycle and escalation followed a 3 þ 3 design in moderate and severe impairment cohorts. Blood samples for detailed pharmacokinetic analyses were collected after the first dose. Results: Thirty-one patients received one dose of romidepsin and were evaluable for pharmacokinetic analyses in normal (n ¼ 12), mild (n ¼ 8), moderate (n ¼ 5), and severe (n ¼ 6) cohorts. Adverse events across cohorts were similar, and dose-limiting toxicity occurred in two patients (mild and severe impairment cohorts). The MTD was not determined because the geometric mean AUC values of romidepsin in moderate (7 mg/m2) and severe (5 mg/m2) impairment cohort were 114% and 116% of the normal cohort (14 mg/m2). Conclusions: Data from the ETCTN-9008 trial led to changes in the romidepsin labeling to reflect starting dose adjustment for patients with cancer and moderate and severe hepatic impairment, with no adjustment for mild hepatic impairment.
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U2 - 10.1158/1078-0432.CCR-20-1412
DO - 10.1158/1078-0432.CCR-20-1412
M3 - Article
C2 - 32816943
AN - SCOPUS:85101318513
SN - 1078-0432
VL - 26
SP - 5329
EP - 5337
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 20
ER -