Mucocutaneous side effects of Brequinar sodium. A new inhibitor of pyrimidine de novo biosynthesis.
Brequinar sodium (NSC 368390; DUP 785) is a new inhibitor of pyrimidine de novo biosynthesis which has completed Phase I clinical trials within the framework of the Early Clinical Trials Group of the European Organization for Research and Treatment of Cancer (EORTC). The main side effects of this compound are myelosuppression, nausea and vomiting, stomatitis and/or mucositis, and skin rash. In this report, the authors describe the pattern of mucocutaneous side effects of Brequinar sodium in patients who received the drug by four different schedules: (1) short-term intravenous (IV) infusion every 3 weeks; (2) weekly; (3) twice weekly; and (4) five times daily every 4 weeks. Mucocutaneous toxicities of Brequinar sodium included mainly cytotoxic reactions (stomatitis and/or mucositis and skin rash). However, rare episodes of local reactions (phlebitis at the site of injection), photosensitivity reactions (to sun light), angioneurotic edema, and localized secondary hyperpigmentation of the inflamed skin also occurred. Stomatitis and/or mucositis appeared to be dose-dependent and schedule-dependent. The skin rash consisted of a drug-induced toxic dermatitis which occurred mostly at the highest dose levels. Initial recommendations for the management of mucocutaneous toxicities of Brequinar sodium during Phase II trials are discussed.
Schwartsmann
G
G
Department of Oncology, Free University, Amsterdam, The Netherlands.
Bork
E
E
Vermorken
J B
JB
Nieboer
C
C
Dodion
P
P
ten Bokkel Huinink
W W
WW
Seldenrijk
C A
CA
Armand
J P
JP
Pinedo
H M
HM
D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D003967:Diarrhea / Q000139:chemically induced; D004334:Drug Administration Schedule; D003875:Drug Eruptions / Q000209:etiology*; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000187:drug effects; D009325:Nausea / Q000139:chemically induced; D009369:Neoplasms / Q000188:drug therapy; D012883:Skin Ulcer / Q000209:etiology; D013280:Stomatitis / Q000139:chemically induced; D014839:Vomiting / Q000139:chemically induced; D011798:Quinaldines
D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; C046943:brequinar; D011798:Quinaldines