Combined weekly topotecan and biweekly bevacizumab in women with platinum-resistant ovarian, peritoneal, or fallopian tube cancer: Results of a Phase 2 Study

Kathryn F. McGonigle, Howard G. Muntz, Jacqueline Vuky, Pamela J. Paley, Dan S. Veljovich, Benjamin E. Greer, Barbara A. Goff, Heidi J. Gray, Thomas W. Malpass

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Abstract

BACKGROUND: A phase 2 trial was conducted to determine the toxicity and efficacy of combined weekly topotecan and biweekly bevacizumab in patients with primary or secondary platinum-resistant ovarian, peritoneal, or fallopian tube cancer (OC). METHODS: Patients were treated with bevacizumab 10 mg/kg on days 1 and 15 and topotecan 4 mg/m2 on days 1, 8, and 15 of a 28-day cycle until progressive disease (PD) or excessive toxicity. The primary endpoint was progression-free survival (PFS); secondary objectives included overall survival (OS), objective response, and toxicity. RESULTS: Patients (N = 40) received a median of 8 treatment cycles. Toxicity was generally mild or moderate, with neutropenia (18%), hypertension (20%), gastrointestinal toxicity (18%), pain (13%), metabolic toxicity (15%), bowel obstruction (10%), and cardiotoxicity (8%) being the most common grade 3 and 4 adverse events. No bowel perforations, febrile neutropenia, or treatment-related deaths occurred. Median PFS and OS were 7.8 (95% confidence interval [CI], 3.0-9.4) and 16.6 months (95% CI, 12.8-22.9), with 22 (55%) patients progression-free for ≥6 months. Ten (25%) patients had partial response (PR), 14 (35%) had stable disease (SD), and 16 (40%) had PD. Patients treated with 2 prior regimens received greater benefit than patients treated with 1: PR/SD, 78.9% versus 42.9% (P =.03); median PFS, 10.9 versus 2.8 months (P =.08); median OS, 22.9 versus 12.8 months (P =.02). CONCLUSIONS: A weekly topotecan and biweekly bevacizumab combination demonstrates acceptable toxicity and encouraging efficacy in patients with platinum-resistant OC; further study is warranted.

Original languageEnglish (US)
Pages (from-to)3731-3740
Number of pages10
JournalCancer
Volume117
Issue number16
DOIs
StatePublished - Aug 15 2011
Externally publishedYes

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Fallopian Tube Neoplasms
Topotecan
Platinum
Disease-Free Survival
Survival
Confidence Intervals
Febrile Neutropenia
Bevacizumab
Neutropenia
Hypertension
Pain

Keywords

  • angiogenesis inhibitors
  • fallopian tube cancer
  • ovarian cancer
  • primary peritoneal carcinoma
  • topotecan, chemotherapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Combined weekly topotecan and biweekly bevacizumab in women with platinum-resistant ovarian, peritoneal, or fallopian tube cancer : Results of a Phase 2 Study. / McGonigle, Kathryn F.; Muntz, Howard G.; Vuky, Jacqueline; Paley, Pamela J.; Veljovich, Dan S.; Greer, Benjamin E.; Goff, Barbara A.; Gray, Heidi J.; Malpass, Thomas W.

In: Cancer, Vol. 117, No. 16, 15.08.2011, p. 3731-3740.

Research output: Contribution to journalArticle

McGonigle, KF, Muntz, HG, Vuky, J, Paley, PJ, Veljovich, DS, Greer, BE, Goff, BA, Gray, HJ & Malpass, TW 2011, 'Combined weekly topotecan and biweekly bevacizumab in women with platinum-resistant ovarian, peritoneal, or fallopian tube cancer: Results of a Phase 2 Study', Cancer, vol. 117, no. 16, pp. 3731-3740. https://doi.org/10.1002/cncr.25967
McGonigle, Kathryn F. ; Muntz, Howard G. ; Vuky, Jacqueline ; Paley, Pamela J. ; Veljovich, Dan S. ; Greer, Benjamin E. ; Goff, Barbara A. ; Gray, Heidi J. ; Malpass, Thomas W. / Combined weekly topotecan and biweekly bevacizumab in women with platinum-resistant ovarian, peritoneal, or fallopian tube cancer : Results of a Phase 2 Study. In: Cancer. 2011 ; Vol. 117, No. 16. pp. 3731-3740.
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abstract = "BACKGROUND: A phase 2 trial was conducted to determine the toxicity and efficacy of combined weekly topotecan and biweekly bevacizumab in patients with primary or secondary platinum-resistant ovarian, peritoneal, or fallopian tube cancer (OC). METHODS: Patients were treated with bevacizumab 10 mg/kg on days 1 and 15 and topotecan 4 mg/m2 on days 1, 8, and 15 of a 28-day cycle until progressive disease (PD) or excessive toxicity. The primary endpoint was progression-free survival (PFS); secondary objectives included overall survival (OS), objective response, and toxicity. RESULTS: Patients (N = 40) received a median of 8 treatment cycles. Toxicity was generally mild or moderate, with neutropenia (18{\%}), hypertension (20{\%}), gastrointestinal toxicity (18{\%}), pain (13{\%}), metabolic toxicity (15{\%}), bowel obstruction (10{\%}), and cardiotoxicity (8{\%}) being the most common grade 3 and 4 adverse events. No bowel perforations, febrile neutropenia, or treatment-related deaths occurred. Median PFS and OS were 7.8 (95{\%} confidence interval [CI], 3.0-9.4) and 16.6 months (95{\%} CI, 12.8-22.9), with 22 (55{\%}) patients progression-free for ≥6 months. Ten (25{\%}) patients had partial response (PR), 14 (35{\%}) had stable disease (SD), and 16 (40{\%}) had PD. Patients treated with 2 prior regimens received greater benefit than patients treated with 1: PR/SD, 78.9{\%} versus 42.9{\%} (P =.03); median PFS, 10.9 versus 2.8 months (P =.08); median OS, 22.9 versus 12.8 months (P =.02). CONCLUSIONS: A weekly topotecan and biweekly bevacizumab combination demonstrates acceptable toxicity and encouraging efficacy in patients with platinum-resistant OC; further study is warranted.",
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author = "McGonigle, {Kathryn F.} and Muntz, {Howard G.} and Jacqueline Vuky and Paley, {Pamela J.} and Veljovich, {Dan S.} and Greer, {Benjamin E.} and Goff, {Barbara A.} and Gray, {Heidi J.} and Malpass, {Thomas W.}",
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T1 - Combined weekly topotecan and biweekly bevacizumab in women with platinum-resistant ovarian, peritoneal, or fallopian tube cancer

T2 - Results of a Phase 2 Study

AU - McGonigle, Kathryn F.

AU - Muntz, Howard G.

AU - Vuky, Jacqueline

AU - Paley, Pamela J.

AU - Veljovich, Dan S.

AU - Greer, Benjamin E.

AU - Goff, Barbara A.

AU - Gray, Heidi J.

AU - Malpass, Thomas W.

PY - 2011/8/15

Y1 - 2011/8/15

N2 - BACKGROUND: A phase 2 trial was conducted to determine the toxicity and efficacy of combined weekly topotecan and biweekly bevacizumab in patients with primary or secondary platinum-resistant ovarian, peritoneal, or fallopian tube cancer (OC). METHODS: Patients were treated with bevacizumab 10 mg/kg on days 1 and 15 and topotecan 4 mg/m2 on days 1, 8, and 15 of a 28-day cycle until progressive disease (PD) or excessive toxicity. The primary endpoint was progression-free survival (PFS); secondary objectives included overall survival (OS), objective response, and toxicity. RESULTS: Patients (N = 40) received a median of 8 treatment cycles. Toxicity was generally mild or moderate, with neutropenia (18%), hypertension (20%), gastrointestinal toxicity (18%), pain (13%), metabolic toxicity (15%), bowel obstruction (10%), and cardiotoxicity (8%) being the most common grade 3 and 4 adverse events. No bowel perforations, febrile neutropenia, or treatment-related deaths occurred. Median PFS and OS were 7.8 (95% confidence interval [CI], 3.0-9.4) and 16.6 months (95% CI, 12.8-22.9), with 22 (55%) patients progression-free for ≥6 months. Ten (25%) patients had partial response (PR), 14 (35%) had stable disease (SD), and 16 (40%) had PD. Patients treated with 2 prior regimens received greater benefit than patients treated with 1: PR/SD, 78.9% versus 42.9% (P =.03); median PFS, 10.9 versus 2.8 months (P =.08); median OS, 22.9 versus 12.8 months (P =.02). CONCLUSIONS: A weekly topotecan and biweekly bevacizumab combination demonstrates acceptable toxicity and encouraging efficacy in patients with platinum-resistant OC; further study is warranted.

AB - BACKGROUND: A phase 2 trial was conducted to determine the toxicity and efficacy of combined weekly topotecan and biweekly bevacizumab in patients with primary or secondary platinum-resistant ovarian, peritoneal, or fallopian tube cancer (OC). METHODS: Patients were treated with bevacizumab 10 mg/kg on days 1 and 15 and topotecan 4 mg/m2 on days 1, 8, and 15 of a 28-day cycle until progressive disease (PD) or excessive toxicity. The primary endpoint was progression-free survival (PFS); secondary objectives included overall survival (OS), objective response, and toxicity. RESULTS: Patients (N = 40) received a median of 8 treatment cycles. Toxicity was generally mild or moderate, with neutropenia (18%), hypertension (20%), gastrointestinal toxicity (18%), pain (13%), metabolic toxicity (15%), bowel obstruction (10%), and cardiotoxicity (8%) being the most common grade 3 and 4 adverse events. No bowel perforations, febrile neutropenia, or treatment-related deaths occurred. Median PFS and OS were 7.8 (95% confidence interval [CI], 3.0-9.4) and 16.6 months (95% CI, 12.8-22.9), with 22 (55%) patients progression-free for ≥6 months. Ten (25%) patients had partial response (PR), 14 (35%) had stable disease (SD), and 16 (40%) had PD. Patients treated with 2 prior regimens received greater benefit than patients treated with 1: PR/SD, 78.9% versus 42.9% (P =.03); median PFS, 10.9 versus 2.8 months (P =.08); median OS, 22.9 versus 12.8 months (P =.02). CONCLUSIONS: A weekly topotecan and biweekly bevacizumab combination demonstrates acceptable toxicity and encouraging efficacy in patients with platinum-resistant OC; further study is warranted.

KW - angiogenesis inhibitors

KW - fallopian tube cancer

KW - ovarian cancer

KW - primary peritoneal carcinoma

KW - topotecan, chemotherapy

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