A phase I study of oxaliplatin in combination with gemcitabine: Correlation of clinical outcome with gene expression

Stephen Shibata, Warren Chow, Paul Frankel, Agnes Juhasz, Lucille Leong, Dean Lim, Kim Margolin, Robert Morgan, Edward Newman, George Somlo, Yun Yen, Timothy Synold, David Gandara, Heinz Josef Lenz, James Doroshow

研究成果: 雜誌貢獻文章

3 引文 (Scopus)

摘要

Purpose: Oxaliplatin has in vitro activity similar to or higher than other platinum agents. Preclinically, gemcitabine has demonstrated synergy when combined with platinum compounds. These facts formed the rationale for determining the maximum tolerated dose (MTD) of gemcitabine in combination with oxaliplatin. Methods: Eligible patients with advanced incurable solid tumors were given oxaliplatin 130 mg/m2 as a 2-h infusion on day 1 followed by escalating doses of gemcitabine given over 30 min on day 1 and 8 of a 21-day cycle. Results: A total of 43 patients were enrolled, including 30 patients at the MTD in an expanded cohort. At a gemcitabine dose of 800 mg/m2, 1/6 patients had a dose limiting toxicity (DLT) (grade 3 blurred vision and memory loss). At 1,000 mg/m2, 1/6 patients had a DLT (grade 3 increase in AST). At 1,200 mg/m2, 2/3 patients had a DLT (grade 4 thrombocytopenia and grade 3 confusion). The MTD of gemcitabine with 130 mg/m2 of oxaliplatin was therefore 1,000 mg/m2. The clearances of gemcitabine and ultrafilterable platinum are within the ranges previously reported for single agents. A patient with colon cancer had a partial response, and 21 patients had a best response of stable disease. In patients with tumor biopsies treated at the MTD, decreased ribonucleotide reductase M2 expression correlated with response. Conclusion: Treatment with gemcitabine and oxaliplatin was well tolerated with primarily hematologic toxicity at the MTD. Study of biochemical correlates of response remain of interest althought current results remain exploratory.

原文英語
頁(從 - 到)549-557
頁數9
期刊Cancer Chemotherapy and Pharmacology
59
發行號4
DOIs
出版狀態已發佈 - 三月 1 2007
對外發佈Yes

指紋

oxaliplatin
gemcitabine
Gene expression
Gene Expression
Maximum Tolerated Dose
Toxicity
Platinum
Tumors
Platinum Compounds
Biopsy
Confusion
Memory Disorders

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

引用此文

A phase I study of oxaliplatin in combination with gemcitabine : Correlation of clinical outcome with gene expression. / Shibata, Stephen; Chow, Warren; Frankel, Paul; Juhasz, Agnes; Leong, Lucille; Lim, Dean; Margolin, Kim; Morgan, Robert; Newman, Edward; Somlo, George; Yen, Yun; Synold, Timothy; Gandara, David; Lenz, Heinz Josef; Doroshow, James.

於: Cancer Chemotherapy and Pharmacology, 卷 59, 編號 4, 01.03.2007, p. 549-557.

研究成果: 雜誌貢獻文章

Shibata, S, Chow, W, Frankel, P, Juhasz, A, Leong, L, Lim, D, Margolin, K, Morgan, R, Newman, E, Somlo, G, Yen, Y, Synold, T, Gandara, D, Lenz, HJ & Doroshow, J 2007, 'A phase I study of oxaliplatin in combination with gemcitabine: Correlation of clinical outcome with gene expression', Cancer Chemotherapy and Pharmacology, 卷 59, 編號 4, 頁 549-557. https://doi.org/10.1007/s00280-006-0297-3
Shibata, Stephen ; Chow, Warren ; Frankel, Paul ; Juhasz, Agnes ; Leong, Lucille ; Lim, Dean ; Margolin, Kim ; Morgan, Robert ; Newman, Edward ; Somlo, George ; Yen, Yun ; Synold, Timothy ; Gandara, David ; Lenz, Heinz Josef ; Doroshow, James. / A phase I study of oxaliplatin in combination with gemcitabine : Correlation of clinical outcome with gene expression. 於: Cancer Chemotherapy and Pharmacology. 2007 ; 卷 59, 編號 4. 頁 549-557.
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abstract = "Purpose: Oxaliplatin has in vitro activity similar to or higher than other platinum agents. Preclinically, gemcitabine has demonstrated synergy when combined with platinum compounds. These facts formed the rationale for determining the maximum tolerated dose (MTD) of gemcitabine in combination with oxaliplatin. Methods: Eligible patients with advanced incurable solid tumors were given oxaliplatin 130 mg/m2 as a 2-h infusion on day 1 followed by escalating doses of gemcitabine given over 30 min on day 1 and 8 of a 21-day cycle. Results: A total of 43 patients were enrolled, including 30 patients at the MTD in an expanded cohort. At a gemcitabine dose of 800 mg/m2, 1/6 patients had a dose limiting toxicity (DLT) (grade 3 blurred vision and memory loss). At 1,000 mg/m2, 1/6 patients had a DLT (grade 3 increase in AST). At 1,200 mg/m2, 2/3 patients had a DLT (grade 4 thrombocytopenia and grade 3 confusion). The MTD of gemcitabine with 130 mg/m2 of oxaliplatin was therefore 1,000 mg/m2. The clearances of gemcitabine and ultrafilterable platinum are within the ranges previously reported for single agents. A patient with colon cancer had a partial response, and 21 patients had a best response of stable disease. In patients with tumor biopsies treated at the MTD, decreased ribonucleotide reductase M2 expression correlated with response. Conclusion: Treatment with gemcitabine and oxaliplatin was well tolerated with primarily hematologic toxicity at the MTD. Study of biochemical correlates of response remain of interest althought current results remain exploratory.",
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T2 - Correlation of clinical outcome with gene expression

AU - Shibata, Stephen

AU - Chow, Warren

AU - Frankel, Paul

AU - Juhasz, Agnes

AU - Leong, Lucille

AU - Lim, Dean

AU - Margolin, Kim

AU - Morgan, Robert

AU - Newman, Edward

AU - Somlo, George

AU - Yen, Yun

AU - Synold, Timothy

AU - Gandara, David

AU - Lenz, Heinz Josef

AU - Doroshow, James

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N2 - Purpose: Oxaliplatin has in vitro activity similar to or higher than other platinum agents. Preclinically, gemcitabine has demonstrated synergy when combined with platinum compounds. These facts formed the rationale for determining the maximum tolerated dose (MTD) of gemcitabine in combination with oxaliplatin. Methods: Eligible patients with advanced incurable solid tumors were given oxaliplatin 130 mg/m2 as a 2-h infusion on day 1 followed by escalating doses of gemcitabine given over 30 min on day 1 and 8 of a 21-day cycle. Results: A total of 43 patients were enrolled, including 30 patients at the MTD in an expanded cohort. At a gemcitabine dose of 800 mg/m2, 1/6 patients had a dose limiting toxicity (DLT) (grade 3 blurred vision and memory loss). At 1,000 mg/m2, 1/6 patients had a DLT (grade 3 increase in AST). At 1,200 mg/m2, 2/3 patients had a DLT (grade 4 thrombocytopenia and grade 3 confusion). The MTD of gemcitabine with 130 mg/m2 of oxaliplatin was therefore 1,000 mg/m2. The clearances of gemcitabine and ultrafilterable platinum are within the ranges previously reported for single agents. A patient with colon cancer had a partial response, and 21 patients had a best response of stable disease. In patients with tumor biopsies treated at the MTD, decreased ribonucleotide reductase M2 expression correlated with response. Conclusion: Treatment with gemcitabine and oxaliplatin was well tolerated with primarily hematologic toxicity at the MTD. Study of biochemical correlates of response remain of interest althought current results remain exploratory.

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