Phase II trial of perillyl alcohol (NSC 641066) administered daily in patients with metastatic androgen independent prostate cancer

Liu, Glenn; Oettel, Kurt R.; Bailey, Howard; Ummersen, Lynn Van; Tutsch, Kendra D.; Staab, Mary Jane; Horvath, Dorothea; Alberti, Dona; Arzoomanian, Rhoda Z.; Rezazadeh, Hamied; McGovern, James; Robinson, Emily; DeMets, David L.; Wilding, George

doi:10.1023/a:1025437115182

Cited by 54 publications

(17 citation statements)

References 11 publications

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“…(Lamiaceae) which has been used for treating colds, food allergy, and depression [ 141 , 142 ]. Considering the absence of ICL1 in human, the well-tolerated profile in human, and the fact that Phase II trials have been conducted in patients with cancers, perillyl alcohol might serve as an interesting candidate for antifungal therapies against C. albicans [ 143 , 144 ].…”

Section: Virulence Factorsmentioning

confidence: 99%

Antifungal Compounds againstCandidaInfections from Traditional Chinese Medicine

Liu

Zhang

et al. 2017

BioMed Research International

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Infections caused by Candida albicans, often refractory and with high morbidity and mortality, cause a heavy burden on the public health while the current antifungal drugs are limited and are associated with toxicity and resistance. Many plant-derived molecules including compounds isolated from traditional Chinese medicine (TCM) are reported to have antifungal activity through different targets such as cell membrane, cell wall, mitochondria, and virulence factors. Here, we review the recent progress in the anti-Candida compounds from TCM, as well as their antifungal mechanisms. Considering the diverse targets and structures, compounds from TCM might be a potential library for antifungal drug development.

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Section: Virulence Factorsmentioning

confidence: 99%

Antifungal Compounds againstCandidaInfections from Traditional Chinese Medicine

Liu

Zhang

et al. 2017

BioMed Research International

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“…Based on the collective outcome of the above-mentioned animal studies, POH was formulated in soft gelatin capsules and tested in a number of phase I and II cancer trials, where it was given orally three to four times each day for several months [ 99 , 100 , 101 , 102 , 103 , 104 , 105 ]. However, the results were disappointing.…”

Section: Intranasal Drug Deliverymentioning

confidence: 99%

Perillyl Alcohol and Its Drug-Conjugated Derivatives as Potential Novel Methods of Treating Brain Metastases

Chen

Fonseca

Schönthal

2016

IJMS

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Metastasis to the central nervous system remains difficult to treat, and such patients are faced with a dismal prognosis. The blood-brain barrier (BBB), despite being partially compromised within malignant lesions in the brain, still retains much of its barrier function and prevents most chemotherapeutic agents from effectively reaching the tumor cells. Here, we review some of the recent developments aimed at overcoming this obstacle in order to more effectively deliver chemotherapeutic agents to the intracranial tumor site. These advances include intranasal delivery to achieve direct nose-to-brain transport of anticancer agents and covalent modification of existing drugs to support enhanced penetration of the BBB. In both of these areas, use of the natural product perillyl alcohol, a monoterpene with anticancer properties, contributed to promising new results, which will be discussed here.

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“…d-Limonene and perillyl alcohol suppressed the incorporation of radiolabeled mevalonate into small G-proteins and this action has been attributed to the inhibition of farnesyl protein transferase activity [35]. Phase I studies of d-limonene [36], and phase I [37] and II [38] studies of perillyl alcohol revealed dose-limiting toxicities, such as nausea, vomiting, anorexia, and eructation. The monoterpenoids carveol, uroterpenol, and sobrerol have demonstrated chemopreventive activity against mammary cancer in rats when fed during the initiation phase [39].…”

Section: Monoterpenesmentioning

confidence: 99%

Terpenoids and breast cancer chemoprevention

Rabi

Bishayee

2008

Breast Cancer Res Treat

202

107

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Cancer chemoprevention is defined as the use of natural or synthetic agents that reverse, suppress or arrest carcinogenic and/or malignant phenotype progression towards invasive cancer. Phytochemicals obtained from vegetables, fruits, spices, herbs and medicinal plants, such as terpenoids, carotenoids, flavanoids, phenolic compounds, and other groups of compounds have shown promise in suppressing experimental carcinogenesis in various organs. Recent studies have indicated that mechanisms underlying chemopreventive action may include combinations of anti-oxidant, anti-inflammatory, immune-enhancing, and anti-hormone effects. Further, modification of drug-metabolizing enzymes, and influences on cell cycling and differentiation, induction of apoptosis, and suppression of proliferation and angiogenesis that play a role in the initiation and secondary modification of neoplastic development, have also been under investigation as possible mechanisms. This review will highlight the biological effects of terpenoids as chemopreventive agents on breast epithelial carcinogenesis, and the utility of intermediate biomarkers as indicators of premalignancy. Selected breast chemoprevention trials are discussed with a focus on strategies for trial design, and clinical outcomes. Future directions in the field of chemoprevention are proposed based on recently acquired mechanistic insights into breast carcinogenesis.

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Phase II trial of perillyl alcohol (NSC 641066) administered daily in patients with metastatic androgen independent prostate cancer

Abstract: Perillyl alcohol administered at this dose and formulation did not have any objective clinical activity in this patient population.

Cited by 54 publications

References 11 publications

Antifungal Compounds againstCandidaInfections from Traditional Chinese Medicine

Antifungal Compounds againstCandidaInfections from Traditional Chinese Medicine

Perillyl Alcohol and Its Drug-Conjugated Derivatives as Potential Novel Methods of Treating Brain Metastases

Terpenoids and breast cancer chemoprevention

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