The dose was rounded ARQ197 Tivantinib to 200 mgm2 as the ganetespib RP2D administered on Days 1, 8, 15 of a 28 day cycle. Toxicity All patients experienced at least one AE. The most common toxicities reported during the study treat ment are Inhibitors,Modulators,Libraries listed in Table 2, and were diarrhea and fa tigue, with Grade 1 and 2 reported in 47 and 30 patients, respectively. The incidence of diarrhea and fatigue increased with higher ganetespib doses. In most patients, the onset of diarrhea occurred between days 17, and generally resolved with anti diarrheal treatment. Other frequent AEs were mainly gastrointestinal, such as abdominal pain, nausea and vomiting, and were mild to moderate. Elevated hepatic enzymes were infrequent and gener ally Grade 1 or 2. Ten, 9, and 6 patients had transient ALP, AST, and ALT elevation, re spectively.

Four patients had Grade 2 or 3 hyberbilirubinemia. however, the events were not con sidered study drug related, as most of these patients presented with extensive hepatic metastases. Eight patients had visual changes, which were mild and transient. Three patients experienced Grade 1 or 2 blurred vision at doses of 35 mgm2, 114 mgm2 and 150 mgm2. Grade 1 Inhibitors,Modulators,Libraries transient visual impairment was reported in 2 patients each case considered to be possibly related to study drug. Other changes were Grade 1 conjunctiv itis, eyelid edema, and night blindness, which were study drug unrelated. One patient with a history of coronary artery disease had Grade 1 atrio ventricular block at 259 mgm2, which was possibly related to study drug.

Three patients expe rienced QTc prolongation at higher dose levels on Cycle 1 Day 1 post dose when QT438 ms, and QTc457. however, a repeat ECG Inhibitors,Modulators,Libraries performed later on the same day showed resolution of the reported changes, with QT414 ms and QTc433. QTc changes were reported in 48 patients that were not symptomatic, did not lead to brady arrhythmias, and were not considered clinically mean ingful by an independent cardiologist who reviewed the ECG data. No clinically significant changes were detected in the vital sign measurements at any dose level. The most common Inhibitors,Modulators,Libraries hematological toxicities considered by the investigators to be treatment related were anemia and neutropenia, occurring in 3 patients each. A total of 36 patients experienced Grade 3 or 4 AE at some point in their participation, with fatigue being the most Inhibitors,Modulators,Libraries commonly reported event.

The number of patients with on treatment SAEs is shown in Table 4. None of the observed SAEs were considered treatment related. selleck chemicals Three deaths were reported during the study. none was deemed to be treatment related. The causes of death were hepatic failure, intestinal obstruction, and respira tory failure. Clinical activity Forty two patients were evaluable for clinical activity, and 11 patients discontinued treatment before first dis ease assessment.