TY - JOUR
T1 - A Phase I/II Study of Evofosfamide, A Hypoxia-activated Prodrug with or without Bortezomib in Subjects with Relapsed/ Refractory Multiple Myeloma
AU - Laubach, Jacob P.
AU - Liu, Chia Jen
AU - Raje, Noopur S.
AU - Yee, Andrew J.
AU - Armand, Philippe
AU - Schlossman, Robert L.
AU - Rosenblatt, Jacalyn
AU - Hedlund, Jacquelyn
AU - Martin, Michael
AU - Reynolds, Craig
AU - Shain, Kenneth H.
AU - Zackon, Ira
AU - Stampleman, Laura
AU - Henrick, Patrick
AU - Rivotto, Bradley
AU - Hornburg, Kalvis T.V.
AU - Dumke, Henry J.
AU - Chuma, Stacey
AU - Savell, Alexandra
AU - Handisides, Damian R.
AU - Kroll, Stew
AU - Anderson, Kenneth C.
AU - Richardson, Paul G.
AU - Ghobrial, Irene M.
N1 - Publisher Copyright:
© 2018 American Association for Cancer Research.
PY - 2019/1/15
Y1 - 2019/1/15
N2 - Purpose: The presence of hypoxia in the diseased bone higher doses. For the combination of evofosfamide, borte-marrow presents a new therapeutic target for multiple mye-zomib, and dexamethasone, no patient had a dose-limiting loma. Evofosfamide (formerly TH-302) is a 2-nitroimidazole toxicity (DLT) and the recommended phase II dose was prodrug of the DNA alkylator, bromo-isophosphoramide established at 340 mg/m 2 . The most common grade 3 mustard, which is selectively activated under hypoxia. This adverse events (AE) were thrombocytopenia (25 patients), trial was designed as a phase I/II study investigating evofosfa-anemia (24 patients), neutropenia (15 patients), and leu-mide in combination with dexamethasone, and in combina-kopenia (9 patients). Skin toxicity was reported in 42 (71%) tion with bortezomib and dexamethasone in relapsed/refrac-patients. Responses included 1 very good partial response tory multiple myeloma. (VGPR), 3 partial response (PR), 2 minor response (MR), 20 Patients and Methods: Fifty-nine patients initiated therapy, stable disease (SD), and 4 progressive disease (PD) for 31 received the combination of evofosfamide and dexameth-evofosfamide þ dexamethasone and 1 complete response asone, and 28 received the combination of evofosfamide, (CR), 2 PR, 1 MR, 18 SD, and 5 PD for evofosfamide þ bortezomib, and dexamethasone. Patients were heavily pre-bortezomib þ dexamethasone. Disease stabilization was treated with a median number of prior therapies of 7 (range: observed in over 80% and this was reflective of the pro-2–15). All had previously received bortezomib and immuno-longed overall survival of 11.2 months. modulators. The MTD, treatment toxicity, and efficacy were Conclusions: Evofosfamide can be administered at 340 determined. mg/m 2 twice a week with or without bortezomib. Clinical Results: The MTD was established at 340 mg/m 2 evofos-activity has been noted in patients with heavily pretreated famide þ dexamethasone with dose-limiting mucositis at relapsed refractory multiple myeloma.
AB - Purpose: The presence of hypoxia in the diseased bone higher doses. For the combination of evofosfamide, borte-marrow presents a new therapeutic target for multiple mye-zomib, and dexamethasone, no patient had a dose-limiting loma. Evofosfamide (formerly TH-302) is a 2-nitroimidazole toxicity (DLT) and the recommended phase II dose was prodrug of the DNA alkylator, bromo-isophosphoramide established at 340 mg/m 2 . The most common grade 3 mustard, which is selectively activated under hypoxia. This adverse events (AE) were thrombocytopenia (25 patients), trial was designed as a phase I/II study investigating evofosfa-anemia (24 patients), neutropenia (15 patients), and leu-mide in combination with dexamethasone, and in combina-kopenia (9 patients). Skin toxicity was reported in 42 (71%) tion with bortezomib and dexamethasone in relapsed/refrac-patients. Responses included 1 very good partial response tory multiple myeloma. (VGPR), 3 partial response (PR), 2 minor response (MR), 20 Patients and Methods: Fifty-nine patients initiated therapy, stable disease (SD), and 4 progressive disease (PD) for 31 received the combination of evofosfamide and dexameth-evofosfamide þ dexamethasone and 1 complete response asone, and 28 received the combination of evofosfamide, (CR), 2 PR, 1 MR, 18 SD, and 5 PD for evofosfamide þ bortezomib, and dexamethasone. Patients were heavily pre-bortezomib þ dexamethasone. Disease stabilization was treated with a median number of prior therapies of 7 (range: observed in over 80% and this was reflective of the pro-2–15). All had previously received bortezomib and immuno-longed overall survival of 11.2 months. modulators. The MTD, treatment toxicity, and efficacy were Conclusions: Evofosfamide can be administered at 340 determined. mg/m 2 twice a week with or without bortezomib. Clinical Results: The MTD was established at 340 mg/m 2 evofos-activity has been noted in patients with heavily pretreated famide þ dexamethasone with dose-limiting mucositis at relapsed refractory multiple myeloma.
UR - http://www.scopus.com/inward/record.url?scp=85060015524&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-18-1325
DO - 10.1158/1078-0432.CCR-18-1325
M3 - Article
C2 - 30279233
AN - SCOPUS:85060015524
SN - 1078-0432
VL - 25
SP - 478
EP - 486
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 2
ER -
