Clinical Significance of Serum Vascular Endothelial Growth Factor Levels in Patients with Advanced Non-Small Cell Lung cancer

PurposeAZD2171 is a potent inhibitor of vascular endothelial growth factor receptors that showed broad antitumor activity in preclinical models. Doses of up to 45 mg/d of AZD2171 are tolerable when administered alone. This study evaluated escalating doses of AZD2171 in combination with standard chemotherapy in patients with advanced non–small-cell lung cancer.Patients and MethodsEligible patients received carboplatin targeted to an area under the concentration time curve of 6 mg · min/mL and paclitaxel 200 mg/m2, both on day 1 of a 3-week cycle; daily oral AZD2171 at either 30 mg or 45 mg commenced day 2 of cycle 1. Pharmacokinetics of all drugs were performed, and tumor response was assessed by Response Evaluation Criteria in Solid Tumors (RECIST).ResultsTwenty patients were enrolled. No dose-limiting toxicities were observed during cycle 1 at either dose. Fatigue, diarrhea, anorexia, and granulocytopenia were common; hypertension was manageable with a treatment algorithm designed for this protocol. No clinically significant drug-related bleeding was observed. At 45 mg/d, fatigue and diarrhea were increased, and headache and hoarseness were observed. Paclitaxel clearance decreased during cycle 2, but no other significant pharmacokinetic interactions were observed. After radiology review, confirmed responses were observed in nine patients (response rate, 45%; 95% CI, 23% to 68%); all but one enrolled patient showed evidence of tumor shrinkage, some with cavitation.ConclusionAZD2171 can be combined with standard doses of carboplatin/paclitaxel with encouraging antitumor activity. Toxicity is increased, but predictable and manageable.

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The Importance of Vascular Endothelial Growth Factor as a Marker of Angiogenesis and Lymphangiogenesis in Non-small Cell Lung Cancer

Acta Medica Marisiensis ◽

10.1515/amma-2015-0077 ◽

2015 ◽

Vol 61 (4) ◽

pp. 367-371 ◽

Cited By ~ 1

Author(s):

Suciu Bogdan Andrei ◽

Denes Lorand ◽

Hălmaciu Ioana ◽

Mezei Tibor ◽

Brînzaniuc Klara ◽

...

Keyword(s):

Lung Cancer ◽

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Prognostic Impact ◽

Vascular Endothelial ◽

Small Cell Lung ◽

Endothelial Growth Factor

AbstractLung cancer is the main cause of cancer death both in men and women. In spite of progress seen in the early diagnosis of lung cancer, and implementation of new treatment principles for these patients, 5 year survival of non-small cell lung cancer patients undergoing surgery is low. Introduction of anti-angiogenic therapy administered concomitantly with conventional chemotherapy agents represented practically the first success seen in the treatment of lung cancer in the last 20 years. The aim of this paper is to review the literature informations about the importance of VEGF (vascular endothelial growth factor) as a marker of angiogenesis in patients with non-small cell lung cancer. Therefore, we practiced a literature review about these topics: the importance of VEGF in tumor angiogenesis and lymphangiogenesis in patients with non-small cell lung cancer and his importance as a prognostic factor at these patients, the prognostic impact of serum levels of VEGF and of the cellular expression of VEGF at these patients and also we reviewed the value of the antiangiogenic therapy.

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The expression of vascular endothelial growth factor C and its receptors in non-small cell lung cancer

British Journal of Cancer ◽

10.1054/bjoc.2001.1882 ◽

2001 ◽

Vol 85 (2) ◽

pp. 255-260 ◽

Cited By ~ 114

Author(s):

T Kajita ◽

Y Ohta ◽

K Kimura ◽

M Tamura ◽

Y Tanaka ◽

...

Keyword(s):

Lung Cancer ◽

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Vascular Endothelial ◽

Small Cell Lung ◽

Factor C ◽

Endothelial Growth Factor

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Prognostic and predictive value of vascular endothelial growth factor and soluble flt-1 and kdr levels in the sera of small cell lung cancer patients

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.21152 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 21152-21152

Author(s):

Z. Ustuner ◽

P. Saip ◽

V. Yasasever ◽

B. Ozturk ◽

B. Vural ◽

...

Keyword(s):

Lung Cancer ◽

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Vascular Endothelial ◽

Small Cell Lung ◽

Endothelial Growth Factor ◽

Pretreatment Serum

21152 Background: Small cell lung cancer (SCLC) has a rapid growth rate, and is characterized by early metastases. Tumor growth is dependent on angiogenesis. Vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis. Whether surveillance of pre and post treatment serum VEGF and its receptors Flt-1 and Kdr levels in SCLC patients have impact on clinical outcome is unknown. Methods: From February 2001- January 2003, 39 consecutive patients (34 male, 5 female) with histologically proven SCLC were enrolled into the study. The patients were staged as limited and extensive according to the Veterans Administration Lung Group (VALSG). Pre treatment (n:39) and post treatment (n:25) serum samples of the same patients after 3 months of treatment were collected. The levels of VEGF and its receptors Flt-1 and kdr are measured in the serum by quantitative sandwich enzyme immunoassay technique. Statistical analysis was performed using the SPSS 10.0 pocket program. Results: The median pretreatment serum VEGF, Flt-1, and Kdr levels were 1,200 pg/ml (range, 1,414.3±956.2 pg/ml), 85 pg/ml (range, 97.8±70.7 pg/ml), and 11,550 pg/ml (range, 14,481±6,267 pg/ml) respectively. The pretreatment serum VEGF, Flt-1, and Kdr concentrations were not different in limited and extensive stages. We detected a poor but positive correlation between VEGF and Kdr (r=0.46, p=0.003). Pretreatment low serum VEGF value (<728.5 pg/ml) and good response to treatment were found as good prognostic factors in multivariate analysis. Surveillance of serum VEGF and Flt-1, Kdr values did not correlate with clinical parameters. Conclusions: Serum VEGF was found to be a significant and independent prognostic factor in SCLC patients. We showed a limited association between serum levels of VEGF and Kdr. Whether the levels of serum VEGF and its receptors Flt-1 and kdr have value in detecting treatment modalities of SCLC needs further studies. No significant financial relationships to disclose.

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