Peripheral motor neuropathy occurred in 1 individual (1.9?%; grade 2). most common grade 3 non-hematological toxicities were fatigue (9.6?%), decreased hunger (7.7?%), sensory neuropathy (5.8?%), and diarrhea (5.8?%). Grade 3/4 neutropenia occurred in 46.2?% of individuals. Conclusions Ixabepilone is definitely active in Asian individuals with advanced gastric malignancy and shows a toxicity profile much like those previously reported in additional tumor types. (%)12 (23.1)Gender, (%)?Male34 (65.4)?Female18 (34.6)Ethnicity, (%)?Chinese23 (44.2)?Japanese15 (28.9)?Korean13 (25.0)?Asian additional1 (1.9)ECOG performance status, (%)?020 (38.5)?132 (61.5)Quantity of disease sites, (%)?111 (21.2)?213 (25.0)?328 (53.8)Disease sites, (%)?Lymph node37 (71.2)?Gastric29 (55.8)?Peritoneum (including ascites)23 (44.2)?Liver19 (36.5)?Lung8 (15.4)?Other30 (57.7) Open in a separate windows Eastern Cooperative Oncology Group Exposure Ixabepilone was administered for any median of 3.5 courses (range: 1C10). Of the 45 individuals who received at least 2 programs, 18 (40?%) required at least 1 dose reduction of ixabepilone. The reasons for the first dose reduction included hematologic toxicity in 6 individuals (13.3?%), neuropathy in 4 individuals (8.9?%), and additional non-hematologic toxicity in 8 individuals (17.8?%). Rabbit polyclonal to LIPH Effectiveness The ORR with ixabepilone therapy was 15.4?% (95?% CI 6.9C28.1); all objective reactions were PR (Table?2). Twenty-six additional individuals (50.0?%) experienced SD and, consequently, the DCR was 65.4?% (95?% CI 50.9C78.0). For individuals achieving PR, the median time to response was 8.9?weeks (range: 5.1C12.1?weeks) and the median period of response was 3.1?weeks (95?% CI 2.6C4.1?weeks). Median EG01377 TFA PFS was 2.8?weeks (95?% CI 2.1C3.5?weeks) (Fig.?1). Table?2 Best overall response (%)?CR0 (0)?PR8 (15.4)?SD26 (50.0)?Progressive disease15 (28.8)?Unable to determine3 (5.8)ORR (95?% CI)15.4 (6.9C28.1)DCR (95?% CI)65.4 (50.9C78.0) Open in a separate window Open in a separate windows Fig.?1 KaplanCMeier plot of progression-free survival Safety The adverse events reported were consistent with the known safety profile of ixabepilone. Fifty individuals (96.2?%) experienced at least 1 adverse event, most commonly alopecia, decreased hunger, neutropenia, peripheral sensory neuropathy, and fatigue (Table?3). Most non-hematologic toxicity was grade 1 or 2 2; the most common grade 3 events were fatigue (9.6?%), decreased hunger (7.7?%), peripheral sensory neuropathy (5.8?%), and diarrhea (5.8?%). Overall, peripheral neuropathies were reported by 33 individuals (63.5?%), with the most common forms becoming peripheral sensory neuropathy (48.1?%) and hypoesthesia (11.5?%). Peripheral engine neuropathy occurred in 1 patient (1.9?%; grade 2). In terms of hematological toxicity, grade 3/4 neutropenia and leukopenia occurred in 24 (46.2?%) and 11 (21.1?%) individuals, respectively, with febrile neutropenia in 4 individuals (7.7?%). Grade 3 anemia and thrombocytopenia occurred in 3 (5.8?%) EG01377 TFA and 2 (3.8?%) individuals, respectively. Table?3 Treatment-related adverse events (AEs) reported at an incidence 10?% thead th align=”remaining” rowspan=”1″ colspan=”1″ AE /th th align=”remaining” rowspan=”1″ colspan=”1″ Grade 1 /th th align=”remaining” rowspan=”1″ colspan=”1″ Grade 2 /th th align=”remaining” rowspan=”1″ colspan=”1″ Grade 3 /th th align=”remaining” rowspan=”1″ colspan=”1″ Grade 4 /th th align=”remaining” rowspan=”1″ colspan=”1″ Total /th /thead Any AE7 (13.5)11 (21.2)12 (23.1)19 (36.5)50 (96.2)a Hematologic AEs?Neutropenia0 (0)2 (3.8)8 (15.4)16 (30.8)26 (50.0)?Leukopenia0 (0)1 (1.9)9 (17.3)2 (3.8)12 (23.1)Non-hematologic AEs?Alopecia26 (50.0)9 (17.3)0 (0)0 (0)35 (67.3)?Decreased appetite14 (26.9)11 (21.2)4 (7.7)0 (0)29 (55.8)?Peripheral sensory neuropathy12 (23.1)10 (19.2)3 (5.8)0 (0)25 (48.1)?Fatigue5 (9.6)12 (23.1)5 (9.6)0 (0)22 (42.3)?Rash11 (21.2)5 (9.6)1 (1.9)0 (0)17 (32.7)?Diarrhea10 (19.2)1 (1.9)3 (5.8)0 (0)14 (26.9)?Constipation9 (17.3)4 (7.7)0 (0)0 (0)13 (25.0)?Nausea8 (15.4)4 (7.7)1 (1.9)0 (0)13 (25.0)?Myalgia9 (17.3)2 (3.8)1 (1.9)0 (0)12 (23.1)?Arthralgia7 (13.5)4 (7.7)0 (0)0 (0)11 (21.2)?Excess weight decreased2 (3.8)9 (17.3)0 (0)0 (0)11 (21.2)?Pruritus6 (11.5)3 (5.8)0 (0)0 (0)9 (17.3)?Pyrexia8 (15.4)0 (0)0 (0)0 (0)8 (15.4)?Vomiting5 (9.6)3 (5.8)0 (0)0 (0)8 (15.4)?Stomatitis2 (3.8)3 (5.8)2 (3.8)0 (0)7 (13.5)?Asthenia1 (1.9)5 (9.6)0 (0)0 (0)6 (11.5)?Dysgeusia5 (9.6)1 (1.9)0 (0)0 (0)6 (11.5)?Hypoesthesia2 (3.8)3 (5.8)1 (1.9)0 (0)6 (11.5)?Nail disorder5 (9.6)0 (0)1 (1.9)0 (0)6 (11.5) Open in a separate window aIncludes 1 patient with grade 5 pneumonia and neutropenic sepsis Four individuals (7.7?%) discontinued treatment because of drug-related adverse events, including 3 individuals with peripheral neuropathy and 1 patient with febrile neutropenia. There was 1 death because of drug-related toxicity: a 69-year-old male patient died of pneumonia and neutropenic sepsis during program 6 of ixabepilone therapy. The patient started program 6 with a reduced dose of 32?mg/m2 because the investigator had considered the patient too weak to continue at the initial dose. The death occurred 18?days after the last treatment. Three additional individuals died within 30?days of their last dose of ixabepilone, all of which were assessed from EG01377 TFA the investigator while due to disease progression. Conversation The results of this phase II study demonstrate that ixabepilone offers activity of medical interest when given at a dose of 40?mg/m2 every 21?days to Asian individuals with unresectable or metastatic gastric malignancy who also had progressed on or within 12?months after receiving fluoropyrimidine-based therapy. With this population, ixabepilone.