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 > or = 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/m(2)/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 (C (max)) was 14.20 microg/mL (range 1.41 to 119 microg /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.
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 > or = 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/m(2)/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 (C (max)) was 14.20 microg/mL (range 1.41 to 119 microg /mL) with no accumulation observed between cycles 1-6. CONCLUSION: This phase II study of nolatrexed in advanced HCCpatients, demonstrated minimal activity and significant stomatitis. Hence, it does not warrant further study as a single agent for this disease.
Authors: I Rafi; A V Boddy; J A Calvete; G A Taylor; D R Newell; N P Bailey; M J Lind; M Green; J Hines; A Johnstone; N Clendeninn; A H Calvert Journal: J Clin Oncol Date: 1998-03 Impact factor: 44.544
Authors: H Tsukuma; T Hiyama; S Tanaka; M Nakao; T Yabuuchi; T Kitamura; K Nakanishi; I Fujimoto; A Inoue; H Yamazaki Journal: N Engl J Med Date: 1993-06-24 Impact factor: 91.245
Authors: S E Webber; T M Bleckman; J Attard; J G Deal; V Kathardekar; K M Welsh; S Webber; C A Janson; D A Matthews; W W Smith Journal: J Med Chem Date: 1993-03-19 Impact factor: 7.446
Authors: Abeer M El-Naggar; Mohsen M Abou-El-Regal; Souad A El-Metwally; Farag F Sherbiny; Ibrahim H Eissa Journal: Mol Divers Date: 2017-08-16 Impact factor: 2.943