Randomized trial of oral cyclophosphamide versus oral cyclophosphamide with celecoxib for recurrent epithelial ovarian, fallopian tube, and primary peritoneal cancer

R. Gupta, Mihaela Cristea, Paul Frankel, Christopher Ruel, Chen Chen, Yingyu Wang, Robert Morgan, Lucille Leong, Warren Chow, Marianna Koczywas, S. Koehler, Dean Lim, Thehang Luu, Cynthia Martel, Mark McNamara, George Somlo, Przemyslaw Twardowski, Yun Yen, Amanam Idorenyi, Tinsley Raechelle & 2 others Mary Carroll, Vincent Chung

Research output: Contribution to journalArticle

Abstract

Background: Oral metronomic chemotherapy, which has low toxicity, has demonstrated promising anti-tumor and anti-angiogenic properties that may lead to prolonged progression-free survival and improved response rates in patients with recurrent epithelial ovarian cancer (EOC). These effects may be enhanced by the co-administration of anti-angiogenic agents. Methods: We conducted a randomized phase II clinical trial to evaluate the therapeutic benefit of oral metronomic cyclophosphamide (CTX) alone and with the anti-angiogenic drug celecoxib in patients with gynecological malignancies. 52 patients were randomly assigned to two treatments arms: 50 mg oral CTX daily alone (Arm A) or with 400 mg celecoxib twice daily (Arm B). The primary endpoint was response rate. Secondary endpoints included toxicity, time to treatment failure, and overall survival. Results: In Arm A (n = 26), 3 patients (12%) had stable disease >6 months and 1 (4%) had a partial response. In Arm B, 5 (19%) had stable disease >6 months and 1 patient (4%) had a partial response. There were no significant between-group differences in overall survival (9.69 months [95% CI 3.84–13.18] vs. 12.55 months [6.67–17.61]) or in median time to treatment failure (1.84 months [1.68–2.76] vs. 1.92 months [1.64–5.22]). The most common adverse events were nausea, vomiting, and abdominal pain. Conclusions: Oral metronomic CTX has activity with no major toxicities in heavily pretreated recurrent gynecological cancers and may be considered in patients with indolent disease. We did not observe any additional benefit of celecoxib treatment, though this may be due to small sample sizes.

Original languageEnglish
Article number100155
JournalCancer Treatment and Research Communications
Volume21
DOIs
Publication statusPublished - Jan 1 2019
Externally publishedYes

Fingerprint

Celecoxib
Fallopian Tubes
Cyclophosphamide
Neoplasms
Treatment Failure
Phase II Clinical Trials
Angiogenesis Inhibitors
Survival
Sample Size
Nausea
Abdominal Pain
Disease-Free Survival
Vomiting
Therapeutics
Randomized Controlled Trials

Keywords

  • Celecoxib
  • Oral cyclophosphamide
  • Ovarian cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Randomized trial of oral cyclophosphamide versus oral cyclophosphamide with celecoxib for recurrent epithelial ovarian, fallopian tube, and primary peritoneal cancer. / Gupta, R.; Cristea, Mihaela; Frankel, Paul; Ruel, Christopher; Chen, Chen; Wang, Yingyu; Morgan, Robert; Leong, Lucille; Chow, Warren; Koczywas, Marianna; Koehler, S.; Lim, Dean; Luu, Thehang; Martel, Cynthia; McNamara, Mark; Somlo, George; Twardowski, Przemyslaw; Yen, Yun; Idorenyi, Amanam; Raechelle, Tinsley; Carroll, Mary; Chung, Vincent.

In: Cancer Treatment and Research Communications, Vol. 21, 100155, 01.01.2019.

Research output: Contribution to journalArticle

Gupta, R, Cristea, M, Frankel, P, Ruel, C, Chen, C, Wang, Y, Morgan, R, Leong, L, Chow, W, Koczywas, M, Koehler, S, Lim, D, Luu, T, Martel, C, McNamara, M, Somlo, G, Twardowski, P, Yen, Y, Idorenyi, A, Raechelle, T, Carroll, M & Chung, V 2019, 'Randomized trial of oral cyclophosphamide versus oral cyclophosphamide with celecoxib for recurrent epithelial ovarian, fallopian tube, and primary peritoneal cancer', Cancer Treatment and Research Communications, vol. 21, 100155. https://doi.org/10.1016/j.ctarc.2019.100155
Gupta, R. ; Cristea, Mihaela ; Frankel, Paul ; Ruel, Christopher ; Chen, Chen ; Wang, Yingyu ; Morgan, Robert ; Leong, Lucille ; Chow, Warren ; Koczywas, Marianna ; Koehler, S. ; Lim, Dean ; Luu, Thehang ; Martel, Cynthia ; McNamara, Mark ; Somlo, George ; Twardowski, Przemyslaw ; Yen, Yun ; Idorenyi, Amanam ; Raechelle, Tinsley ; Carroll, Mary ; Chung, Vincent. / Randomized trial of oral cyclophosphamide versus oral cyclophosphamide with celecoxib for recurrent epithelial ovarian, fallopian tube, and primary peritoneal cancer. In: Cancer Treatment and Research Communications. 2019 ; Vol. 21.
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abstract = "Background: Oral metronomic chemotherapy, which has low toxicity, has demonstrated promising anti-tumor and anti-angiogenic properties that may lead to prolonged progression-free survival and improved response rates in patients with recurrent epithelial ovarian cancer (EOC). These effects may be enhanced by the co-administration of anti-angiogenic agents. Methods: We conducted a randomized phase II clinical trial to evaluate the therapeutic benefit of oral metronomic cyclophosphamide (CTX) alone and with the anti-angiogenic drug celecoxib in patients with gynecological malignancies. 52 patients were randomly assigned to two treatments arms: 50 mg oral CTX daily alone (Arm A) or with 400 mg celecoxib twice daily (Arm B). The primary endpoint was response rate. Secondary endpoints included toxicity, time to treatment failure, and overall survival. Results: In Arm A (n = 26), 3 patients (12{\%}) had stable disease >6 months and 1 (4{\%}) had a partial response. In Arm B, 5 (19{\%}) had stable disease >6 months and 1 patient (4{\%}) had a partial response. There were no significant between-group differences in overall survival (9.69 months [95{\%} CI 3.84–13.18] vs. 12.55 months [6.67–17.61]) or in median time to treatment failure (1.84 months [1.68–2.76] vs. 1.92 months [1.64–5.22]). The most common adverse events were nausea, vomiting, and abdominal pain. Conclusions: Oral metronomic CTX has activity with no major toxicities in heavily pretreated recurrent gynecological cancers and may be considered in patients with indolent disease. We did not observe any additional benefit of celecoxib treatment, though this may be due to small sample sizes.",
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T1 - Randomized trial of oral cyclophosphamide versus oral cyclophosphamide with celecoxib for recurrent epithelial ovarian, fallopian tube, and primary peritoneal cancer

AU - Gupta, R.

AU - Cristea, Mihaela

AU - Frankel, Paul

AU - Ruel, Christopher

AU - Chen, Chen

AU - Wang, Yingyu

AU - Morgan, Robert

AU - Leong, Lucille

AU - Chow, Warren

AU - Koczywas, Marianna

AU - Koehler, S.

AU - Lim, Dean

AU - Luu, Thehang

AU - Martel, Cynthia

AU - McNamara, Mark

AU - Somlo, George

AU - Twardowski, Przemyslaw

AU - Yen, Yun

AU - Idorenyi, Amanam

AU - Raechelle, Tinsley

AU - Carroll, Mary

AU - Chung, Vincent

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: Oral metronomic chemotherapy, which has low toxicity, has demonstrated promising anti-tumor and anti-angiogenic properties that may lead to prolonged progression-free survival and improved response rates in patients with recurrent epithelial ovarian cancer (EOC). These effects may be enhanced by the co-administration of anti-angiogenic agents. Methods: We conducted a randomized phase II clinical trial to evaluate the therapeutic benefit of oral metronomic cyclophosphamide (CTX) alone and with the anti-angiogenic drug celecoxib in patients with gynecological malignancies. 52 patients were randomly assigned to two treatments arms: 50 mg oral CTX daily alone (Arm A) or with 400 mg celecoxib twice daily (Arm B). The primary endpoint was response rate. Secondary endpoints included toxicity, time to treatment failure, and overall survival. Results: In Arm A (n = 26), 3 patients (12%) had stable disease >6 months and 1 (4%) had a partial response. In Arm B, 5 (19%) had stable disease >6 months and 1 patient (4%) had a partial response. There were no significant between-group differences in overall survival (9.69 months [95% CI 3.84–13.18] vs. 12.55 months [6.67–17.61]) or in median time to treatment failure (1.84 months [1.68–2.76] vs. 1.92 months [1.64–5.22]). The most common adverse events were nausea, vomiting, and abdominal pain. Conclusions: Oral metronomic CTX has activity with no major toxicities in heavily pretreated recurrent gynecological cancers and may be considered in patients with indolent disease. We did not observe any additional benefit of celecoxib treatment, though this may be due to small sample sizes.

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KW - Ovarian cancer

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