Abstract：
:Between February 1987 and July 1988, 45 patients with advanced refractory cancer were treated with LY186641, a diarylsulfonylurea that has shown a broad spectrum of activity in preclinical testing. Patients received a weekly p.o. dose of LY186641 for 6 consecutive weeks; responding and stable patients continued weekly therapy until progression occurred. Using a standard phase I study design, the first three patients received LY186641 at 30 mg/m2 week; the dose was escalated in subsequent patients until dose-limiting toxicity occurred. Methemoglobinemia was the major toxicity observed and was dose related. Methemoglobin levels peaked approximately 24 h after LY186641 was administered and fell to low levels after 48 h. Six patients developed fatigue, cyanosis, and dyspnea associated with serum methemoglobinemia levels of greater than 20%; four of these patients were subsequently removed from the study. Hemolytic anemia was also observed but was clinically significant in only 10 patients. Other side effects were mild and infrequent. The maximum tolerated dose of LY186641, when given at this schedule, was 2550 mg/m2/week. No objective tumor responses were observed.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Hainsworth JD,Hande KR,Satterlee WG,Kuttesch J,Johnson DH,Grindey G,Jackson LE,Greco FAsubject
Has Abstractpub_date
1989-09-15 00:00:00pages
5217-20issue
18eissn
0008-5472issn
1538-7445journal_volume
49pub_type
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