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Clinical Trial
. 2019:21:100155.
doi: 10.1016/j.ctarc.2019.100155. Epub 2019 Jul 3.

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

Rohan Gupta  1 , Mihaela Cristea  1 , Paul Frankel  2 , Christopher Ruel  2 , Chen Chen  3 , Yingyu Wang  3 , Robert Morgan  1 , Lucille Leong  1 , Warren Chow  1 , Marianna Koczywas  1 , Steve Koehler  1 , Dean Lim  1 , Thehang Luu  1 , Cynthia Martel  1 , Mark McNamara  1 , George Somlo  1 , Przemyslaw Twardowski  1 , Yun Yen  1 , Amanam Idorenyi  1 , Tinsley Raechelle  4 , Mary Carroll  4 , Vincent Chung  5
Affiliations
Clinical Trial

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

Rohan Gupta et al. Cancer Treat Res Commun. 2019.

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.

Keywords: Celecoxib; Oral cyclophosphamide; Ovarian cancer.

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Figures

Figure 1.
Figure 1.
Summary of patient responses.
Figure 2.
Figure 2.
Correlation of (a) baseline and (b) change in CA 125 with duration of treatment.
Figure 3.
Figure 3.
Overall survival (OS) of patients in treatment arms A and B.
Figure 4.
Figure 4.
Time to treatment failure (TTF) of patients in treatment groups A and B.
See this image and copyright information in PMC

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