A phase I study of oral ZD 1839 given daily in patients with solid tumors: IND.122, a study of the Investigational New Drug Program of the National Cancer Institute of Canada Clinical Trials Group

Goss, Glenwood D.; Hirte, Hal W.; Miller, Wilson H.; Lorimer, Ian A. J.; Stewart, David J.; Batist, Gerald; Parolin, Doris A. E.; Hanna, Peter; Stafford, Shawn J.; Friedmann, Jennifer; Walsh, William R.; Mathews, Sara; Douglas, L.; Seymour, Lesley

doi:10.1007/s10637-005-5860-y

Cited by 42 publications

(31 citation statements)

References 20 publications

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“…ZD1839 was given as a single daily dose of 750 mg. This dose was based on the results of the phase I study of oral ZD1839 conducted by NCIC CTG [20]. The agent was taken one hour prior to breakfast except on day 1 when an additional loading dose was given.…”

Section: Dosing and Drug Administrationmentioning

confidence: 99%

“…The National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) recently completed a phase I dose-escalating trial of ZD1839 [20]. Twenty-eight patients were enrolled at doses ranging from 150 to 800 mg daily.…”

Section: Introductionmentioning

confidence: 99%

“…This trial was conducted as a dose expansion study of the original phase I trial [20], involving only patients with metastatic colorectal cancer.…”

Section: Introductionmentioning

confidence: 99%

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A phase II trial of ZD1839 (Iressa™) 750 mg per day, an oral epidermal growth factor receptor-tyrosine kinase inhibitor, in patients with metastatic colorectal cancer

et al. 2005

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Section: Dosing and Drug Administrationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A phase II trial of ZD1839 (Iressa™) 750 mg per day, an oral epidermal growth factor receptor-tyrosine kinase inhibitor, in patients with metastatic colorectal cancer

et al. 2005

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“…[41][42][43][44][45] Intermittent and daily dose schedules ranging from 50 mg to 1000 mg per day were assessed. Adverse events were generally mild, i.e.…”

Section: Clinical Studies Phase I Studiesmentioning

confidence: 99%

Management of EGFR-Mutant Non-Small Cell Lung Cancer: Focus on Gefitinib

Naito

Goto

2009

Clinical Medicine. Therapeutics

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Gefitinib is a first generation, reversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), and EGFR TKIs, such as gefitinib and erlotinib, have yielded dramatic and durable responses in approximately 75% of of non-small cell lung cancer (NSCLC) patients whose tumor has an activating EGFR mutation. EGFR mutations are found in approximately 10%-15% of lung cancers in Caucasians, and they are more frequent in female patients, patients with adenocarcinoma, patients who are neversmokers or have a history of light-smoking, and patients with Asian ethnicity. Recent phase III trials comparing gefitinib with standard chemotherapy have demonstrated a similar survival benefit of gefitinib in patients with NSCLC and improved quality of life both in a first-line setting (IPASS; comparing gefitinib with carboplatin/paclitaxel) and a previously-treated setting (INTEREST; comparing gefitinib with docetaxel). Subset analyses of the data obtained in these studies showed that in patients with EGFR-mutant NSCLC gefitinib yielded a higher response rate, longer progression-free survival, and similar overall survival than standard cytotoxic chemotherapy did. The toxicity of EGFR TKIs is generally milder than that of standard cytotoxic chemotherapy. This review focuses on gefitinib, and issues in the management of EGFR-mutant NSCLC are discussed.

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“…Phase I studies were conducted with various cancer types, including breast, ovarian, colorectal, head and neck cancer and mostly NSCLC [3][4][5][6][7]. Dose limiting toxicity was reached at doses from 700 mg/day to 1,000 mg/day.…”

Section: Preclinical Data / Phase I Studiesmentioning

confidence: 99%

Clinical and Preclinical Experience with Gefitinib and Sunitinib

Fasching¹,

Lux²,

Rauh³

et al. 2007

Breast Care

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Gefitinib and sunitinib are new targeted agents in cancer therapy. As a single-target agent gefitinib was one of the first tyrosine kinase inhibitors in solid cancers. It is an inhibitor of the intracellular domain of the epidermal growth factor receptor (EGFR). Most experience with this drug was made in the treatment of non-small cell lung cancer. Its efficacy in most other solid cancers is limited. Several studies could show an association between the response of non-small cell lung cancers to gefitinib and a mutation of the EGFR gene. This mutation changes the target and alters the sensitivity for the drug. In breast cancer limited data of phase II studies showed response rates lower than 2%. Sunitinib as a multitarget agent inhibits several targets like vascular epidermal growth factor receptors (VEGFR) and other receptor tyrosine kinases. The efficacy of sunitinib against tumors is attributable to a direct antitumor activity and to an inhibition of neoangiogenesis. Most data exist for the treatment of metastatic renal cell carcinoma and gastrointestinal stromal tumors. Sunitinib could clearly improve the systemic treatment of these diseases. In the treatment of metastatic breast cancer response rates for the single agent therapy of 11% could be reported, which made this agent interesting for further phase III studies. These phase III studies are currently ongoing.

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A phase I study of oral ZD 1839 given daily in patients with solid tumors: IND.122, a study of the Investigational New Drug Program of the National Cancer Institute of Canada Clinical Trials Group

Abstract: It appears that ZD 1839 at a dose of 800 m/day was tolerable, although some patients required dose modification for diarrhea. Doses above 250 m/day demonstrate biologic activity and could be consider for future study in a variety of EGFR positive tumor types.

Cited by 42 publications

References 20 publications

A phase II trial of ZD1839 (Iressa™) 750 mg per day, an oral epidermal growth factor receptor-tyrosine kinase inhibitor, in patients with metastatic colorectal cancer

A phase II trial of ZD1839 (Iressa™) 750 mg per day, an oral epidermal growth factor receptor-tyrosine kinase inhibitor, in patients with metastatic colorectal cancer

Management of EGFR-Mutant Non-Small Cell Lung Cancer: Focus on Gefitinib

Clinical and Preclinical Experience with Gefitinib and Sunitinib

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