Activity of multitargeted antifolate (Pemetrexed disodium, LY231514) in patients with advanced colorectal carcinoma: Results from a phase II study

William John, Joel Picus, Charles Blanke, Jeffery W. Clark, Lawrence N. Schulman, Eric K. Rowinsky, Donald E. Thornton, Patrick J. Loehrer

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

BACKGROUND. The aim of this study was to confirm the activity and assess the safety profile of multitargeted antifolate (MTA) for patients with metastatic colorectal adenocarcinoma. METHODS. Forty-six patients were enrolled in the study, 35 with colon and 11 with rectal carcinoma. Adjuvant therapy was allowed if completed 1 year previously. Patients received MTA 600 mg/m2 as a 10-minute intravenous infusion once every 21 days. Blood samples were taken every cycle for pharmacokinetic and vitamin metabolite assays. RESULTS. Among 39 patients eligible for efficacy analysis, 1 complete response and 5 partial responses were identified, for an overall response rate of 15.4% (95% confidence interval [CI], 4.1-26.7%) for all patients. Fifteen patients had stable disease, with 9 living longer than 1 year. The median survival was 16.2 months (95% CI, 10.5-17.0%); 65% of patients were alive at 1 year, and the median time to progression was 4.4 months (range, 3.2-5.7 months). The main toxicides were hematologic, with common toxicity criteria (CTC) Grades 3 or 4 noted as follows: thrombocytopenia (18%), neutropenia (55%), and anemia (18%). Nonhematologic toxicities included Grade 2 or 3 skin reaction (53%), ameliorated by dexamethasone, and Grade 3 transaminases (23%). Dose omissions were not required and 21% of doses were reduced. CONCLUSIONS. MTA has clear activity in patients with colorectal carcinoma, and encouraging survival times were noted. MTA was well tolerated in this patient group, but myelosuppression was frequent. Toxicity may be increased with folate deficiency. (C) 2000 American Cancer Society.

Original languageEnglish (US)
Pages (from-to)1807-1813
Number of pages7
JournalCancer
Volume88
Issue number8
DOIs
StatePublished - Apr 15 2000
Externally publishedYes

Fingerprint

Pemetrexed
Folic Acid Antagonists
Colorectal Neoplasms
Confidence Intervals
Survival
Transaminases
Neutropenia
Folic Acid
Intravenous Infusions
Vitamins
Thrombocytopenia
Dexamethasone
Anemia
Colon
Adenocarcinoma

Keywords

  • Advanced colorectal carcinoma
  • Metastasis
  • Multitargeted antifolate LY231514

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Activity of multitargeted antifolate (Pemetrexed disodium, LY231514) in patients with advanced colorectal carcinoma : Results from a phase II study. / John, William; Picus, Joel; Blanke, Charles; Clark, Jeffery W.; Schulman, Lawrence N.; Rowinsky, Eric K.; Thornton, Donald E.; Loehrer, Patrick J.

In: Cancer, Vol. 88, No. 8, 15.04.2000, p. 1807-1813.

Research output: Contribution to journalArticle

John, William ; Picus, Joel ; Blanke, Charles ; Clark, Jeffery W. ; Schulman, Lawrence N. ; Rowinsky, Eric K. ; Thornton, Donald E. ; Loehrer, Patrick J. / Activity of multitargeted antifolate (Pemetrexed disodium, LY231514) in patients with advanced colorectal carcinoma : Results from a phase II study. In: Cancer. 2000 ; Vol. 88, No. 8. pp. 1807-1813.
@article{4b49078467f24453ba340bf4beafd2f0,
title = "Activity of multitargeted antifolate (Pemetrexed disodium, LY231514) in patients with advanced colorectal carcinoma: Results from a phase II study",
abstract = "BACKGROUND. The aim of this study was to confirm the activity and assess the safety profile of multitargeted antifolate (MTA) for patients with metastatic colorectal adenocarcinoma. METHODS. Forty-six patients were enrolled in the study, 35 with colon and 11 with rectal carcinoma. Adjuvant therapy was allowed if completed 1 year previously. Patients received MTA 600 mg/m2 as a 10-minute intravenous infusion once every 21 days. Blood samples were taken every cycle for pharmacokinetic and vitamin metabolite assays. RESULTS. Among 39 patients eligible for efficacy analysis, 1 complete response and 5 partial responses were identified, for an overall response rate of 15.4{\%} (95{\%} confidence interval [CI], 4.1-26.7{\%}) for all patients. Fifteen patients had stable disease, with 9 living longer than 1 year. The median survival was 16.2 months (95{\%} CI, 10.5-17.0{\%}); 65{\%} of patients were alive at 1 year, and the median time to progression was 4.4 months (range, 3.2-5.7 months). The main toxicides were hematologic, with common toxicity criteria (CTC) Grades 3 or 4 noted as follows: thrombocytopenia (18{\%}), neutropenia (55{\%}), and anemia (18{\%}). Nonhematologic toxicities included Grade 2 or 3 skin reaction (53{\%}), ameliorated by dexamethasone, and Grade 3 transaminases (23{\%}). Dose omissions were not required and 21{\%} of doses were reduced. CONCLUSIONS. MTA has clear activity in patients with colorectal carcinoma, and encouraging survival times were noted. MTA was well tolerated in this patient group, but myelosuppression was frequent. Toxicity may be increased with folate deficiency. (C) 2000 American Cancer Society.",
keywords = "Advanced colorectal carcinoma, Metastasis, Multitargeted antifolate LY231514",
author = "William John and Joel Picus and Charles Blanke and Clark, {Jeffery W.} and Schulman, {Lawrence N.} and Rowinsky, {Eric K.} and Thornton, {Donald E.} and Loehrer, {Patrick J.}",
year = "2000",
month = "4",
day = "15",
doi = "10.1002/(SICI)1097-0142(20000415)88:8<1807::AID-CNCR8>3.0.CO;2-L",
language = "English (US)",
volume = "88",
pages = "1807--1813",
journal = "Cancer",
issn = "0008-543X",
publisher = "John Wiley and Sons Inc.",
number = "8",

}

TY - JOUR

T1 - Activity of multitargeted antifolate (Pemetrexed disodium, LY231514) in patients with advanced colorectal carcinoma

T2 - Results from a phase II study

AU - John, William

AU - Picus, Joel

AU - Blanke, Charles

AU - Clark, Jeffery W.

AU - Schulman, Lawrence N.

AU - Rowinsky, Eric K.

AU - Thornton, Donald E.

AU - Loehrer, Patrick J.

PY - 2000/4/15

Y1 - 2000/4/15

N2 - BACKGROUND. The aim of this study was to confirm the activity and assess the safety profile of multitargeted antifolate (MTA) for patients with metastatic colorectal adenocarcinoma. METHODS. Forty-six patients were enrolled in the study, 35 with colon and 11 with rectal carcinoma. Adjuvant therapy was allowed if completed 1 year previously. Patients received MTA 600 mg/m2 as a 10-minute intravenous infusion once every 21 days. Blood samples were taken every cycle for pharmacokinetic and vitamin metabolite assays. RESULTS. Among 39 patients eligible for efficacy analysis, 1 complete response and 5 partial responses were identified, for an overall response rate of 15.4% (95% confidence interval [CI], 4.1-26.7%) for all patients. Fifteen patients had stable disease, with 9 living longer than 1 year. The median survival was 16.2 months (95% CI, 10.5-17.0%); 65% of patients were alive at 1 year, and the median time to progression was 4.4 months (range, 3.2-5.7 months). The main toxicides were hematologic, with common toxicity criteria (CTC) Grades 3 or 4 noted as follows: thrombocytopenia (18%), neutropenia (55%), and anemia (18%). Nonhematologic toxicities included Grade 2 or 3 skin reaction (53%), ameliorated by dexamethasone, and Grade 3 transaminases (23%). Dose omissions were not required and 21% of doses were reduced. CONCLUSIONS. MTA has clear activity in patients with colorectal carcinoma, and encouraging survival times were noted. MTA was well tolerated in this patient group, but myelosuppression was frequent. Toxicity may be increased with folate deficiency. (C) 2000 American Cancer Society.

AB - BACKGROUND. The aim of this study was to confirm the activity and assess the safety profile of multitargeted antifolate (MTA) for patients with metastatic colorectal adenocarcinoma. METHODS. Forty-six patients were enrolled in the study, 35 with colon and 11 with rectal carcinoma. Adjuvant therapy was allowed if completed 1 year previously. Patients received MTA 600 mg/m2 as a 10-minute intravenous infusion once every 21 days. Blood samples were taken every cycle for pharmacokinetic and vitamin metabolite assays. RESULTS. Among 39 patients eligible for efficacy analysis, 1 complete response and 5 partial responses were identified, for an overall response rate of 15.4% (95% confidence interval [CI], 4.1-26.7%) for all patients. Fifteen patients had stable disease, with 9 living longer than 1 year. The median survival was 16.2 months (95% CI, 10.5-17.0%); 65% of patients were alive at 1 year, and the median time to progression was 4.4 months (range, 3.2-5.7 months). The main toxicides were hematologic, with common toxicity criteria (CTC) Grades 3 or 4 noted as follows: thrombocytopenia (18%), neutropenia (55%), and anemia (18%). Nonhematologic toxicities included Grade 2 or 3 skin reaction (53%), ameliorated by dexamethasone, and Grade 3 transaminases (23%). Dose omissions were not required and 21% of doses were reduced. CONCLUSIONS. MTA has clear activity in patients with colorectal carcinoma, and encouraging survival times were noted. MTA was well tolerated in this patient group, but myelosuppression was frequent. Toxicity may be increased with folate deficiency. (C) 2000 American Cancer Society.

KW - Advanced colorectal carcinoma

KW - Metastasis

KW - Multitargeted antifolate LY231514

UR - http://www.scopus.com/inward/record.url?scp=0034655141&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034655141&partnerID=8YFLogxK

U2 - 10.1002/(SICI)1097-0142(20000415)88:8<1807::AID-CNCR8>3.0.CO;2-L

DO - 10.1002/(SICI)1097-0142(20000415)88:8<1807::AID-CNCR8>3.0.CO;2-L

M3 - Article

C2 - 10760756

AN - SCOPUS:0034655141

VL - 88

SP - 1807

EP - 1813

JO - Cancer

JF - Cancer

SN - 0008-543X

IS - 8

ER -