Randomized phase II trial of the anti-angiogenic potential of doxorubicin and docetaxel; primary chemotherapy as Biomarker Discovery Laboratory

Kathy D. Miller, Sharon E. Soule, Cynthia Calley, Robert E. Emerson, Gary D. Hutchins, Kenyon Kopecky, Sunil Badve, Anna Maria Storniolo, Robert Goulet, George W. Sledge

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Purpose: Primary chemotherapy provides an ideal opportunity to correlate potential non-invasive surrogate markers of angiogenesis with tumor microvessel density (MVD) and response. Patients and methods: Patients with newly diagnosed stages II or III breast cancer were treated with sequential doxorubicin 75 mg/M2 q2 wks x 3 and docetaxel 40 mg/M2 weekly x 6; treatment order was randomly assigned. Potential serologic and imaging markers of angiogenesis were obtained pre-treatment, at crossover and completion of chemotherapy. Non-invasive biomarkers were correlated with MVD and pathologic response. Results: From June 1999 to October 2002, 70 patients were entered. Median pretreatment tumor diameter was 6.0 cm with clinically involved axillary nodes in 33 (47%) patients; 20% had inflammatory disease. Clinical response rate was 91%, including 46% clinical complete responses. Pathologic complete response (pCR) was confirmed in 9 (12.8%) patients. Baseline MVD did not correlate with clinical or pathologic response. Serologic markers were obtained in all patients; basic fibroblast growth factor (bFGF) was lower at baseline and increased during treatment in patients with a pCR but did not correlate with MVD. Color Doppler ultrasound (CDUS) was completed in 47 patients; no parameter reliably correlated with MVD or response. Positron emission tomography (PET) with [F-18]-fluoro-deoxyglucose, [O-15]-water and [C-11]-carbon monoxide were completed in 19 patients; uptake of all tracers decreased during treatment in virtually all patients. Conclusion: Sequential doxorubicin and docetaxel is generally well tolerated and highly active. Serum angiogenic factors and imaging parameters frequently varied throughout treatment but did not correlate with MVD or consistently predict response.

Original languageEnglish (US)
Pages (from-to)187-197
Number of pages11
JournalBreast Cancer Research and Treatment
Volume89
Issue number2
DOIs
StatePublished - Jan 1 2005

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docetaxel
Doxorubicin
Biomarkers
Drug Therapy
Microvessels
Therapeutics
Doppler Ultrasonography
Angiogenesis Inducing Agents
Deoxyglucose

Keywords

  • Basic fibroblast growth factor (bFGF)
  • Color Doppler ultrasound
  • Microvessel density
  • Positron emission tomography
  • Vascular cell adhesion molecule-1 (VCAM-1)

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Randomized phase II trial of the anti-angiogenic potential of doxorubicin and docetaxel; primary chemotherapy as Biomarker Discovery Laboratory. / Miller, Kathy D.; Soule, Sharon E.; Calley, Cynthia; Emerson, Robert E.; Hutchins, Gary D.; Kopecky, Kenyon; Badve, Sunil; Storniolo, Anna Maria; Goulet, Robert; Sledge, George W.

In: Breast Cancer Research and Treatment, Vol. 89, No. 2, 01.01.2005, p. 187-197.

Research output: Contribution to journalArticle

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abstract = "Purpose: Primary chemotherapy provides an ideal opportunity to correlate potential non-invasive surrogate markers of angiogenesis with tumor microvessel density (MVD) and response. Patients and methods: Patients with newly diagnosed stages II or III breast cancer were treated with sequential doxorubicin 75 mg/M2 q2 wks x 3 and docetaxel 40 mg/M2 weekly x 6; treatment order was randomly assigned. Potential serologic and imaging markers of angiogenesis were obtained pre-treatment, at crossover and completion of chemotherapy. Non-invasive biomarkers were correlated with MVD and pathologic response. Results: From June 1999 to October 2002, 70 patients were entered. Median pretreatment tumor diameter was 6.0 cm with clinically involved axillary nodes in 33 (47{\%}) patients; 20{\%} had inflammatory disease. Clinical response rate was 91{\%}, including 46{\%} clinical complete responses. Pathologic complete response (pCR) was confirmed in 9 (12.8{\%}) patients. Baseline MVD did not correlate with clinical or pathologic response. Serologic markers were obtained in all patients; basic fibroblast growth factor (bFGF) was lower at baseline and increased during treatment in patients with a pCR but did not correlate with MVD. Color Doppler ultrasound (CDUS) was completed in 47 patients; no parameter reliably correlated with MVD or response. Positron emission tomography (PET) with [F-18]-fluoro-deoxyglucose, [O-15]-water and [C-11]-carbon monoxide were completed in 19 patients; uptake of all tracers decreased during treatment in virtually all patients. Conclusion: Sequential doxorubicin and docetaxel is generally well tolerated and highly active. Serum angiogenic factors and imaging parameters frequently varied throughout treatment but did not correlate with MVD or consistently predict response.",
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AU - Miller, Kathy D.

AU - Soule, Sharon E.

AU - Calley, Cynthia

AU - Emerson, Robert E.

AU - Hutchins, Gary D.

AU - Kopecky, Kenyon

AU - Badve, Sunil

AU - Storniolo, Anna Maria

AU - Goulet, Robert

AU - Sledge, George W.

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KW - Positron emission tomography

KW - Vascular cell adhesion molecule-1 (VCAM-1)

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