Weekly AUC2 carboplatin in acquired platinum-resistant ovarian cancer with or without oral phenoxodiol, a sensitizer of platinum cytotoxicity: the phase III OVATURE multicenter randomized study

Fotopoulou, Christina; Vergote, Ignace; Mainwaring, Paul N.; Bidziński, Mariusz; Vermorken, Jan B.; Ghamande, Sharad; Harnett, Paul; Prete, Salvatore A. Del; Green, J.A.; Spaczyński, Marek; Blagden, Sarah P.; Gore, Martin; Ledermann, Jonathan A.; Kaye, SB; Gabra, Hani

doi:10.1093/annonc/mdt515

Cited by 27 publications

(17 citation statements)

References 24 publications

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“…As for efficacy, our study shows a better RR, including CR lasting more than 3 years, compared with OVATURE [22], OVA301 [23] and ASSIST-5 studies [24], although PFS is in the same range. The CARTAXHY trial [25] shows a better RR and PFS compared with other studies, even in a paclitaxel single-agent arm.…”

Section: Discussionmentioning

confidence: 63%

Phase II trial of oral etoposide plus intravenous irinotecan in patients with platinum-resistant and taxane-pretreated ovarian cancer (JCOG0503)

Matsumoto

Katsumata

Shibata

et al. 2015

Gynecologic Oncology

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Section: Discussionmentioning

confidence: 63%

Phase II trial of oral etoposide plus intravenous irinotecan in patients with platinum-resistant and taxane-pretreated ovarian cancer (JCOG0503)

Matsumoto

Katsumata

Shibata

et al. 2015

Gynecologic Oncology

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“…Although no clinical trials have evaluated effects of dietary genistein in CRPC patients while receiving taxane chemotherapy, there are some reports on combination effects of soy/genistein products in combination with chemotherapeutic agents used for other malignancies. Results from a Phase II clinical trial using the synthetic genistein analogue phenoxodiol in combination with chemotherapy (paclitaxel, carboplatin, or cisplatin) in ovarian cancer patients suggested efficacy, but in a subsequent phase III trial the combination of carboplatin and oral phenoxodiol failed to enhance effectiveness of carboplatin alone and no differences in overall survival or progression‐free survival were observed . Consumption of Novasoy, a dietary isoflavone supplement, did not improve outcome of gemcitabine and erlotinib therapy in patients with advanced pancreatic cancer, and adversely affected tolerability of erlotinib .…”

Section: Discussionmentioning

confidence: 95%

Lack of combination effects of soy isoflavones and taxane chemotherapy of castration‐resistant prostate cancer

2018

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Background Patients with cancer, including prostate cancer, often use dietary supplements, such as soy or isoflavones, before, during, or after therapy. There is little information about possible interactions between supplements and cancer chemotherapy. There are some reports suggesting enhancement by genistein of taxane chemotherapy for castrate‐resistant prostate cancer (CRPC). Methods We investigated whether physiologically attainable concentrations of soy isoflavones (≤10 μM) interact with taxanes on growth inhibition of CRPC cells in vitro and in vivo in nude mice exposed via the diet, on microtubule disassembly in vitro, and on P‐glycoprotein‐mediated drug efflux in 22Rv1 cells and CYP3A4 activity in microsomes. Results Genistein, daidzein, and equol did not affect growth of VCaP, 22Rv1, C4‐2, and PC‐3 CRPC cells or growth inhibition of these cells by docetaxel and cabazitaxel. These isoflavones did not inhibit microtubule disassembly in vitro or inhibit the microtubule effects of taxanes and genistein did not bind substantially to microtubules. Genistein considerably inhibited P‐glycoprotein‐mediated drug efflux in 22Rv1 cells and CYP3A4 activity in microsomes. However, dietary supplementation with genistein at 250 and 500 ppm did not affect the tumor growth inhibiting effect of docetaxel on 22Rv1 cells xenografted in nude mice. Conclusions Our results with relevant cell models and clinically achievable concentrations of soy isoflavones do not support the notion that genistein or other soy isoflavones can enhance the effects of taxane chemotherapy in CRPC cell and xenograft models. Yet, the inhibitory effects of genistein on drug efflux in 22Rv1 cells and on microsomal CYP3A4 activity raise the possibility that genistein can affect taxane effects on CRPC cells in other circumstances than those we studied, which merits further research.

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“…The flavone acetic acid (FAA) was used in two clinical trials, one for patients with solid tumors, such as melanoma (Thatcher et al, 1990), and the other for treatment of breast, colon, and head and neck carcinoma and endometrial carcinoma (Kaye et al, 1990). Additionally, two trials used phenoxodiol for ovarian cancer patients (Kelly et al 2011, Fotopoulou et al, 2014, two used isoflavone for prostate cancer (Vaishampayan et al, 2007) and pancreatic cancer patients (El-Rayes et al, 2011), and one used polyphenon E (Shanafelt et al, 2013) for treatment of leukemia, associated or not with the first line chemotherapy drug schema (Table 1).…”

Section: Resultsmentioning

confidence: 99%

Flavonoids as anticancer therapies: A systematic review of clinical trials

Bisol

Campos

Lamers

2019

Phytotherapy Research

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Flavonoids have been proposed as potential chemotherapeutic agents because they are toxic against cancer cells but not harmful to healthy cells. This systematic review analyzed flavonoid effectiveness in human cancer chemotherapy. Overall, 22 phase II and 1 phase III clinical trials (PubMed, Scopus, and Web of Science) that used flavonoids as a single agent or combined with other therapeutics against hematopoietic/lymphoid or solid cancer published by January 2019 were selected for analysis. Flavopiridol was the most commonly used flavonoid (at a dose of 50‐mg/m2 IV) for all tumor types. Aside from the relatively low rate of complete response (CR) or partial response (PR) with any administration protocol, flavonoids showed higher positive outcomes for hematopoietic and lymphoid tissues (140 patients with CR and 88 with PR among 615 patients in 11 trials) than for solid tumors (4 patients with CR and 21 with PR among 525 patients in 12 trials). However, because of the high variety in administration schedule, more studies are needed to further understand how flavonoids can promote positive outcomes for cancer patients.

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Weekly AUC2 carboplatin in acquired platinum-resistant ovarian cancer with or without oral phenoxodiol, a sensitizer of platinum cytotoxicity: the phase III OVATURE multicenter randomized study

Cited by 27 publications

References 24 publications

Phase II trial of oral etoposide plus intravenous irinotecan in patients with platinum-resistant and taxane-pretreated ovarian cancer (JCOG0503)

Phase II trial of oral etoposide plus intravenous irinotecan in patients with platinum-resistant and taxane-pretreated ovarian cancer (JCOG0503)

Lack of combination effects of soy isoflavones and taxane chemotherapy of castration‐resistant prostate cancer

Flavonoids as anticancer therapies: A systematic review of clinical trials

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