Norihiko Sugisawa1,2,3, Takashi Higuchi4,5, Qinghong Han4, Chihiro Hozumi6, Jun Yamamoto4,5, Yoshihiko Tashiro4,5, Hiroto Nishino4,5, Kei Kawaguchi7, Michael Bouvet5, Takuya Murata8, Michiaki Unno9, Robert M Hoffman10,11. 1. AntiCancer, Inc, 7917 Ostrow Street, San Diego, 92111, CA, USA. n.sugisawa@surg.med.tohoku.ac.jp. 2. Department of Surgery, University of California, San Diego, 3855 Health Sciences Drive 0987, La Jolla, 92093, CA, USA. n.sugisawa@surg.med.tohoku.ac.jp. 3. Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan. n.sugisawa@surg.med.tohoku.ac.jp. 4. AntiCancer, Inc, 7917 Ostrow Street, San Diego, 92111, CA, USA. 5. Department of Surgery, University of California, San Diego, 3855 Health Sciences Drive 0987, La Jolla, 92093, CA, USA. 6. AntiCancer Japan, Inc, 2-23-5 Ryukakujidai, Sakae-cho, Imba-gun, Chiba, 270-1505, Japan. 7. Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan. 8. Department of Obstetrics and Gynecology, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192, Japan. 9. Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan. m_unno@surg.med.tohoku.ac.jp. 10. AntiCancer, Inc, 7917 Ostrow Street, San Diego, 92111, CA, USA. all@anticancer.com. 11. Department of Surgery, University of California, San Diego, 3855 Health Sciences Drive 0987, La Jolla, 92093, CA, USA. all@anticancer.com.
Abstract
PURPOSE: Advanced ovarian clear cell carcinoma (OCCC) is a recalcitrant disease, often resistant to the first-line platinum-based therapy. Using a novel patient-derived orthotopic xenograft (PDOX) nude-mouse model of OCCC, we tested whether oral-recombinant methioninase (o-rMETase) could enhance the efficacy of paclitaxel (PTX). METHODS: The OCCC PDOX model was established and passaged in nude mice. The OCCC PDOX models were randomized into 5 groups. G1: untreated control; G2: paclitaxel (PTX) (20 mg/kg, intraperitoneal (i.p.) injection, weekly); G3: o-rMETase (100 units, oral, daily); G4: PTX (20 mg/kg, i.p. injection, weekly) + carboplatinum (CBDCA) (40 mg/kg, i.p. injection weekly); G5: PTX (20 mg/kg, i.p. injection, weekly) + o-rMETase (100 units, oral, daily). The treatment period was 2 weeks. RESULTS: The combination of PTX and o-rMETase arrested OCCC tumor growth (relative tumor volume: 1.09 ± 0.63 (mean ± SD)) compared with the untreated control (relative tumor volume: 3.92 ± 1.04 (mean ± SD)) (p < 0.0001). There was no significant difference in relative tumor volume between PTX plus o-rMETase and PTX plus CBDCA (relative tumor volume: 1.39 ± 0.37 (mean ± SD)) (p = 0.93). CONCLUSION: PTX plus o-rMETase arrested the OCCC tumor growth. o-rMETase is readily administered and can greatly enhance first-line therapy of a recalcitrant cancer. The novel and effective treatment strategy in the present report has future clinical potential for patients with OCCC, especially for patients who cannot well tolerate platinum-based therapy.
PURPOSE: Advanced ovarian clear cell carcinoma (OCCC) is a recalcitrant disease, often resistant to the first-line platinum-based therapy. Using a novel patient-derived orthotopic xenograft (PDOX) nude-mouse model of OCCC, we tested whether oral-recombinant methioninase (o-rMETase) could enhance the efficacy of paclitaxel (PTX). METHODS: The OCCC PDOX model was established and passaged in nude mice. The OCCC PDOX models were randomized into 5 groups. G1: untreated control; G2: paclitaxel (PTX) (20 mg/kg, intraperitoneal (i.p.) injection, weekly); G3: o-rMETase (100 units, oral, daily); G4: PTX (20 mg/kg, i.p. injection, weekly) + carboplatinum (CBDCA) (40 mg/kg, i.p. injection weekly); G5: PTX (20 mg/kg, i.p. injection, weekly) + o-rMETase (100 units, oral, daily). The treatment period was 2 weeks. RESULTS: The combination of PTX and o-rMETase arrested OCCC tumor growth (relative tumor volume: 1.09 ± 0.63 (mean ± SD)) compared with the untreated control (relative tumor volume: 3.92 ± 1.04 (mean ± SD)) (p < 0.0001). There was no significant difference in relative tumor volume between PTX plus o-rMETase and PTX plus CBDCA (relative tumor volume: 1.39 ± 0.37 (mean ± SD)) (p = 0.93). CONCLUSION:PTX plus o-rMETase arrested the OCCC tumor growth. o-rMETase is readily administered and can greatly enhance first-line therapy of a recalcitrant cancer. The novel and effective treatment strategy in the present report has future clinical potential for patients with OCCC, especially for patients who cannot well tolerate platinum-based therapy.
Authors: Lindsey A Torre; Britton Trabert; Carol E DeSantis; Kimberly D Miller; Goli Samimi; Carolyn D Runowicz; Mia M Gaudet; Ahmedin Jemal; Rebecca L Siegel Journal: CA Cancer J Clin Date: 2018-05-29 Impact factor: 508.702
Authors: Catherine A Shu; Qin Zhou; Anjali R Jotwani; Alexia Iasonos; Mario M Leitao; Jason A Konner; Carol A Aghajanian Journal: Gynecol Oncol Date: 2015-09-25 Impact factor: 5.482
Authors: William E Winter; G Larry Maxwell; Chunqiao Tian; Jay W Carlson; Robert F Ozols; Peter G Rose; Maurie Markman; Deborah K Armstrong; Franco Muggia; William P McGuire Journal: J Clin Oncol Date: 2007-08-20 Impact factor: 44.544