TY - JOUR
T1 - Phase II trial of nolatrexed dihydrochloride [Thymitaq™, AG 337] in patients with advanced hepatocellular carcinoma
AU - Jhawer, Minaxi
AU - Rosen, Lee
AU - Dancey, Janet
AU - Hochster, Howard
AU - Hamburg, Solomon
AU - Tempero, Margaret
AU - Clendeninn, Neil
AU - Mani, Sridhar
PY - 2007/2
Y1 - 2007/2
N2 - Background: To evaluate the tolerability and efficacy of nolatrexed in patients with advanced hepatocellular carcinoma. Patients and methods: Forty-eight patients were entered onto this study. Nolatrexed was administered every 3 weeks as a 24-h continuous intravenous infusion of 725 mg/m 2/day for 5 days. Doses were adjusted to maintain a dose level that produced grade 2 toxicity. Response was assessed after every two cycles. Plasma pharmacokinetic samples were assayed using a validated high performance liquid chromatography ultraviolet method. Results: Thirty-nine (81%) patients were evaluable for response. The mean number of cycles received was 2.8 (range 1-12). The mean dose intensity was 700 mg/m2/day (SD of 71). One patient had a partial response (2.6%) for 7 months. Eighteen (46%) patients had SD, 20 (51%) patients had progressive disease. The median duration of SD was 93 days. The median overall survival was 32 weeks [95% CI (22-37)]. The most frequent Grade 3 or 4 adverse events were stomatitis (25%), dehydration (23%) and asthenia (21%). There was no evidence of cumulative toxicity. The overall median plasma concentration (Cmax) was 14.20 μg/mL (range 1.41 to 119 μg /mL) with no accumulation observed between cycles 1-6. Conclusion: This phase II study of nolatrexed in advanced HCC patients, demonstrated minimal activity and significant stomatitis. Hence, it does not warrant further study as a single agent for this disease.
AB - Background: To evaluate the tolerability and efficacy of nolatrexed in patients with advanced hepatocellular carcinoma. Patients and methods: Forty-eight patients were entered onto this study. Nolatrexed was administered every 3 weeks as a 24-h continuous intravenous infusion of 725 mg/m 2/day for 5 days. Doses were adjusted to maintain a dose level that produced grade 2 toxicity. Response was assessed after every two cycles. Plasma pharmacokinetic samples were assayed using a validated high performance liquid chromatography ultraviolet method. Results: Thirty-nine (81%) patients were evaluable for response. The mean number of cycles received was 2.8 (range 1-12). The mean dose intensity was 700 mg/m2/day (SD of 71). One patient had a partial response (2.6%) for 7 months. Eighteen (46%) patients had SD, 20 (51%) patients had progressive disease. The median duration of SD was 93 days. The median overall survival was 32 weeks [95% CI (22-37)]. The most frequent Grade 3 or 4 adverse events were stomatitis (25%), dehydration (23%) and asthenia (21%). There was no evidence of cumulative toxicity. The overall median plasma concentration (Cmax) was 14.20 μg/mL (range 1.41 to 119 μg /mL) with no accumulation observed between cycles 1-6. Conclusion: This phase II study of nolatrexed in advanced HCC patients, demonstrated minimal activity and significant stomatitis. Hence, it does not warrant further study as a single agent for this disease.
KW - Hepatocellular carcinoma
KW - Phase II clinical trial
KW - Thymidylate synthase inhibitors
KW - Thymitaq
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U2 - 10.1007/s10637-006-9003-x
DO - 10.1007/s10637-006-9003-x
M3 - Article
C2 - 16957834
AN - SCOPUS:33750489731
SN - 0167-6997
VL - 25
SP - 85
EP - 94
JO - Investigational New Drugs
JF - Investigational New Drugs
IS - 1
ER -