Phase II study of first-line LY231514 (multi-targeted antifolate) in patients with locally advanced or metastatic colorectal cancer: An NCIC Clinical Trials Group study

Cripps, C.; Burnell, Margot J.; Jolivet, Jacques; Batist, Gerald; Lofters, W.; Dancey, Janet; Iglesias, J.; Fisher, B.; Eisenhauer, E. A.

doi:10.1023/a:1008372529239

Cited by 89 publications

(59 citation statements)

References 7 publications

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“…Pemetrexed 500 or 600 mg/m 2 was administered as a 10-minute infusion once every 21 days. The lower dose of 500 mg/m 2 was instituted due to toxicities seen both in the study by Rusthoven et al [3] and a colorectal study by Cripps et al [6] conducted at the same institution. Results from the study by Rusthoven et al [3] and one by Clarke et al [2] were consistent with regard to end points, with an overall response rate of 23% [3] and 18% [2] (Table 3).…”

Section: Nsclcmentioning

confidence: 99%

Pemetrexed Disodium: A Novel Antifolate Clinically Active Against Multiple Solid Tumors

et al. 2001

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Pemetrexed disodium (ALIMTA ® , "pemetrexed") is a novel, multi-targeted antifolate that has demonstrated promising clinical activity in a wide variety of solid tumors, including non-small cell lung, breast, mesothelioma, colorectal, pancreatic, gastric, bladder, cervix, and head and neck. Pemetrexed inhibits multiple folate-dependent enzymes involved in both purine and pyrimidine synthesis including thymidylate synthase, dihydrofolate reductase, glycinamide ribonucleotide formyltransferase, and aminoimidazole carboxamide ribonucleotide formyltransferase. As a single agent, pemetrexed exhibits a moderate toxicity profile at a dose of 500 mg/m 2 by 10-minute infusion once every 21 days with myelosuppression being the dose-limiting toxicity. Folic acid added to the diet in preclinical studies reduced toxicities while maintaining antitumor activity. Based on this observation and clinical toxicities, folic acid and vitamin B 12 dietary supplementation has been recently introduced into all ongoing trials. Studies combining pemetrexed with other active chemotherapeutic agents demonstrate that these combination therapies may become important treatment regimens in a variety of cancer types. Currently, pemetrexed phase III trials are ongoing in mesothelioma and non-small cell lung cancer with future trials planned to explore this unique multitargeted antifolate.

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Section: Nsclcmentioning

confidence: 99%

Pemetrexed Disodium: A Novel Antifolate Clinically Active Against Multiple Solid Tumors

et al. 2001

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“…The maximum tolerated dose established in Phase I studies of pemetrexed was 600 mg/m 2 every 3 weeks (4,5). This dose was later reduced to 500 mg/m 2 every 3 weeks in several Phase II trials, particularly when used in combination with other cytotoxic agents (6,7). Folic acid and vitamin B 12 supplementation became a requirement for pemetrexed-based therapy early in this study, when analysis of safety data from multiple pemetrexed trials suggested that supplementation may decrease toxicity (8).…”

Section: Introductionmentioning

confidence: 99%

Phase II Study of Pemetrexed-Gemcitabine Combination in Patients with Advanced-Stage Non-Small Cell Lung Cancer

Monnerat

Chevalier

Kelly

et al. 2004

Clinical Cancer Research

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Purpose: Cisplatin is one of the most active agents for the treatment of non-small cell lung cancer (NSCLC). It is also known for significant toxicity, which makes it unsuitable for certain patients. Our purpose was to evaluate the efficacy and toxicity of a promising cisplatin-free combination, gemcitabine plus pemetrexed, in NSCLC.Experimental Design: Chemo-naive patients with inoperable NSCLC were eligible for this study. Gemcitabine (1250 mg/m 2 ) was given intravenously on days 1 and 8, followed by intravenous pemetrexed (500 mg/m 2 ) on day 8. After inclusion of 13 patients, folic acid and vitamin B 12 supplementation was added to lower pemetrexed-induced toxicity. Quality of life was assessed with the Lung Cancer Symptom Scale.Results: Sixty patients enrolled; 58 were evaluable for response. All patients had a World Health Organization performance status of 0 or 1. Eighty-seven percent had stage IV disease. Nine patients had a confirmed partial response [overall response rate, 15.5%; 95% confidence interval (CI), 7.3-27.4%]. Twenty-nine (50.0%) patients had stable disease. Median overall survival was 10.1 months (95% CI, 7.9 -13.0 months), with a 1-and 2-year overall survival of 42.6% (95% CI, 30.0 -55.3%) and 18.5% (95% CI, 7.9 -29.1%). Median progression-free survival was 5.0 months. Median response duration was 3.3 months. There were no deaths attributed to treatment. Common Toxicity Criteria grade 3/4 toxicities were neutropenia (61.7%), febrile neutropenia (16.7%), fatigue (23.3%), and elevations of aspartate aminotransferase (15.0%) and alanine aminotransferase (20.0%).Conclusions: This combination had good tolerance and achieved promising overall survival with extended 1-and 2-year survival rates. This cisplatin-free regimen warrants further evaluation in randomized trials.

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“…Pemetrexed has shown broad clinical antitumor activity in patients with colorectal, pancreatic, and breast cancers (Adjei et al, 2004) and has received regulatory approvals for treating patients with malignant mesothelioma and nonsmall cell lung cancer (Hazarika et al, 2004). Pemetrexed 500-600mg/m² administered every three weeks showed singleagent activity as first-line treatment for advanced CRC in two phase II trials (Cripps et al, 1999;John et al, 2000). The objective responses rates were 15% in the American study (John et al, 2000) and 17% in the Canadian study (Cripps et al, 1999) and the median overall survival times were 16.2 and 15.1 months, respectively.…”

Section: Resultsmentioning

confidence: 99%

“…Pemetrexed 500-600mg/m² administered every three weeks showed singleagent activity as first-line treatment for advanced CRC in two phase II trials (Cripps et al, 1999;John et al, 2000). The objective responses rates were 15% in the American study (John et al, 2000) and 17% in the Canadian study (Cripps et al, 1999) and the median overall survival times were 16.2 and 15.1 months, respectively. The major toxicities of pemetrexed are myelosuppression, skin rash, and mucositis, with neutropenia being the primary doselimiting toxicity (Louvet et al, 2004).…”

Section: Resultsmentioning

confidence: 99%

Pemetrexed is Mildly Active with Good Tolerability for Treatment of Patients with Colorectal Cancer

Zhang

Ping²,

Song³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Phase II study of first-line LY231514 (multi-targeted antifolate) in patients with locally advanced or metastatic colorectal cancer: An NCIC Clinical Trials Group study

Abstract: Single-agent MTA at 500 mg/m2 given every three weeks has modest activity in metastatic colorectal carcinoma.

Cited by 89 publications

References 7 publications

Pemetrexed Disodium: A Novel Antifolate Clinically Active Against Multiple Solid Tumors

Pemetrexed Disodium: A Novel Antifolate Clinically Active Against Multiple Solid Tumors

Phase II Study of Pemetrexed-Gemcitabine Combination in Patients with Advanced-Stage Non-Small Cell Lung Cancer

Pemetrexed is Mildly Active with Good Tolerability for Treatment of Patients with Colorectal Cancer

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