Phase II clinical trial of bevacizumab and low-dose metronomic oral cyclophosphamide in recurrent ovarian cancer

A trial of the California, Chicago, and Princess Margaret Hospital phase II consortia

Agustin A. Garcia, Hal Hirte, Gini Fleming, Dongyun Yang, Denice D. Tsao-Wei, Lynda Roman, Susan Groshen, Steve Swenson, Frank Markland, David R Gandara, Sidney A Scudder, Robert Morgan, Helen Chen, Heinz Josef Lenz, Amit M. Oza

Research output: Contribution to journalArticle

442 Citations (Scopus)

Abstract

Purpose: Vascular endothelial growth factor (VEGF) plays an important role in the biology of ovarian cancer (OC). Inhibitors of VEGF suppress tumor growth in OC models. Metronomic chemotherapy, defined as frequent administration of low doses of cytotoxic chemotherapy, suppresses tumor growth, possibly by inhibiting angiogenesis. A phase II trial was conducted to evaluate the antitumor activity and adverse effects of bevacizumab and metronomic oral cyclophosphamide in women with recurrent OC. Patients and Methods: Patients with measurable disease and prior treatment with a platinum-containing regimen were eligible. Up to two different regimens for recurrent disease were allowed. Treatment consisted of bevacizumab 10 mg/kg intravenously every 2 weeks and oral cyclophosphamide 50 mg/d. The primary end point was progression-free survival at 6 months. Plasma levels of VEGF, E-selectin, and thrombospondin-1 were obtained serially. Results: Seventy patients were enrolled. The probability of being alive and progression free at 6 months was 56% (± 6% SE). A partial response was achieved in 17 patients (24%). Median time to progression and survival were 7.2 and 16.9 months, respectively. The most common serious toxicities were hypertension, fatigue, and pain. Bevacizumab-related toxicities included four episodes of gastrointestinal perforation or fistula, two episodes each of CNS ischemia and pulmonary hypertension, and one episode each of gastrointestinal bleeding and wound healing complication. There were three treatment-related deaths. Levels of VEGF, E-selectin, and thrombospondin-1 were not associated with clinical outcome. Conclusion: The combination of bevacizumab and metronomic cyclophosphamide is active in recurrent OC. Further study of this combination is warranted.

Original languageEnglish (US)
Pages (from-to)76-82
Number of pages7
JournalJournal of Clinical Oncology
Volume26
Issue number1
DOIs
StatePublished - Jan 1 2008
Externally publishedYes

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Phase II Clinical Trials
Ovarian Neoplasms
Cyclophosphamide
Vascular Endothelial Growth Factor A
Thrombospondin 1
E-Selectin
Drug Therapy
Growth
Platinum
Pulmonary Hypertension
Wound Healing
Disease-Free Survival
Fistula
Fatigue
Neoplasms
Therapeutics
Ischemia
Hemorrhage
Hypertension
Pain

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Phase II clinical trial of bevacizumab and low-dose metronomic oral cyclophosphamide in recurrent ovarian cancer : A trial of the California, Chicago, and Princess Margaret Hospital phase II consortia. / Garcia, Agustin A.; Hirte, Hal; Fleming, Gini; Yang, Dongyun; Tsao-Wei, Denice D.; Roman, Lynda; Groshen, Susan; Swenson, Steve; Markland, Frank; Gandara, David R; Scudder, Sidney A; Morgan, Robert; Chen, Helen; Lenz, Heinz Josef; Oza, Amit M.

In: Journal of Clinical Oncology, Vol. 26, No. 1, 01.01.2008, p. 76-82.

Research output: Contribution to journalArticle

Garcia, Agustin A. ; Hirte, Hal ; Fleming, Gini ; Yang, Dongyun ; Tsao-Wei, Denice D. ; Roman, Lynda ; Groshen, Susan ; Swenson, Steve ; Markland, Frank ; Gandara, David R ; Scudder, Sidney A ; Morgan, Robert ; Chen, Helen ; Lenz, Heinz Josef ; Oza, Amit M. / Phase II clinical trial of bevacizumab and low-dose metronomic oral cyclophosphamide in recurrent ovarian cancer : A trial of the California, Chicago, and Princess Margaret Hospital phase II consortia. In: Journal of Clinical Oncology. 2008 ; Vol. 26, No. 1. pp. 76-82.
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abstract = "Purpose: Vascular endothelial growth factor (VEGF) plays an important role in the biology of ovarian cancer (OC). Inhibitors of VEGF suppress tumor growth in OC models. Metronomic chemotherapy, defined as frequent administration of low doses of cytotoxic chemotherapy, suppresses tumor growth, possibly by inhibiting angiogenesis. A phase II trial was conducted to evaluate the antitumor activity and adverse effects of bevacizumab and metronomic oral cyclophosphamide in women with recurrent OC. Patients and Methods: Patients with measurable disease and prior treatment with a platinum-containing regimen were eligible. Up to two different regimens for recurrent disease were allowed. Treatment consisted of bevacizumab 10 mg/kg intravenously every 2 weeks and oral cyclophosphamide 50 mg/d. The primary end point was progression-free survival at 6 months. Plasma levels of VEGF, E-selectin, and thrombospondin-1 were obtained serially. Results: Seventy patients were enrolled. The probability of being alive and progression free at 6 months was 56{\%} (± 6{\%} SE). A partial response was achieved in 17 patients (24{\%}). Median time to progression and survival were 7.2 and 16.9 months, respectively. The most common serious toxicities were hypertension, fatigue, and pain. Bevacizumab-related toxicities included four episodes of gastrointestinal perforation or fistula, two episodes each of CNS ischemia and pulmonary hypertension, and one episode each of gastrointestinal bleeding and wound healing complication. There were three treatment-related deaths. Levels of VEGF, E-selectin, and thrombospondin-1 were not associated with clinical outcome. Conclusion: The combination of bevacizumab and metronomic cyclophosphamide is active in recurrent OC. Further study of this combination is warranted.",
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T1 - Phase II clinical trial of bevacizumab and low-dose metronomic oral cyclophosphamide in recurrent ovarian cancer

T2 - A trial of the California, Chicago, and Princess Margaret Hospital phase II consortia

AU - Garcia, Agustin A.

AU - Hirte, Hal

AU - Fleming, Gini

AU - Yang, Dongyun

AU - Tsao-Wei, Denice D.

AU - Roman, Lynda

AU - Groshen, Susan

AU - Swenson, Steve

AU - Markland, Frank

AU - Gandara, David R

AU - Scudder, Sidney A

AU - Morgan, Robert

AU - Chen, Helen

AU - Lenz, Heinz Josef

AU - Oza, Amit M.

PY - 2008/1/1

Y1 - 2008/1/1

N2 - Purpose: Vascular endothelial growth factor (VEGF) plays an important role in the biology of ovarian cancer (OC). Inhibitors of VEGF suppress tumor growth in OC models. Metronomic chemotherapy, defined as frequent administration of low doses of cytotoxic chemotherapy, suppresses tumor growth, possibly by inhibiting angiogenesis. A phase II trial was conducted to evaluate the antitumor activity and adverse effects of bevacizumab and metronomic oral cyclophosphamide in women with recurrent OC. Patients and Methods: Patients with measurable disease and prior treatment with a platinum-containing regimen were eligible. Up to two different regimens for recurrent disease were allowed. Treatment consisted of bevacizumab 10 mg/kg intravenously every 2 weeks and oral cyclophosphamide 50 mg/d. The primary end point was progression-free survival at 6 months. Plasma levels of VEGF, E-selectin, and thrombospondin-1 were obtained serially. Results: Seventy patients were enrolled. The probability of being alive and progression free at 6 months was 56% (± 6% SE). A partial response was achieved in 17 patients (24%). Median time to progression and survival were 7.2 and 16.9 months, respectively. The most common serious toxicities were hypertension, fatigue, and pain. Bevacizumab-related toxicities included four episodes of gastrointestinal perforation or fistula, two episodes each of CNS ischemia and pulmonary hypertension, and one episode each of gastrointestinal bleeding and wound healing complication. There were three treatment-related deaths. Levels of VEGF, E-selectin, and thrombospondin-1 were not associated with clinical outcome. Conclusion: The combination of bevacizumab and metronomic cyclophosphamide is active in recurrent OC. Further study of this combination is warranted.

AB - Purpose: Vascular endothelial growth factor (VEGF) plays an important role in the biology of ovarian cancer (OC). Inhibitors of VEGF suppress tumor growth in OC models. Metronomic chemotherapy, defined as frequent administration of low doses of cytotoxic chemotherapy, suppresses tumor growth, possibly by inhibiting angiogenesis. A phase II trial was conducted to evaluate the antitumor activity and adverse effects of bevacizumab and metronomic oral cyclophosphamide in women with recurrent OC. Patients and Methods: Patients with measurable disease and prior treatment with a platinum-containing regimen were eligible. Up to two different regimens for recurrent disease were allowed. Treatment consisted of bevacizumab 10 mg/kg intravenously every 2 weeks and oral cyclophosphamide 50 mg/d. The primary end point was progression-free survival at 6 months. Plasma levels of VEGF, E-selectin, and thrombospondin-1 were obtained serially. Results: Seventy patients were enrolled. The probability of being alive and progression free at 6 months was 56% (± 6% SE). A partial response was achieved in 17 patients (24%). Median time to progression and survival were 7.2 and 16.9 months, respectively. The most common serious toxicities were hypertension, fatigue, and pain. Bevacizumab-related toxicities included four episodes of gastrointestinal perforation or fistula, two episodes each of CNS ischemia and pulmonary hypertension, and one episode each of gastrointestinal bleeding and wound healing complication. There were three treatment-related deaths. Levels of VEGF, E-selectin, and thrombospondin-1 were not associated with clinical outcome. Conclusion: The combination of bevacizumab and metronomic cyclophosphamide is active in recurrent OC. Further study of this combination is warranted.

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