Phase I dose escalation trial of docetaxel plus curcumin in patients with advanced and metastatic breast cancer

Bayet-Robert, Mathilde; Kwiatkowski, Fabrice; Leheurteur, Marianne; Gachon, F.; Planchat, E.; Abrial, Catherine; Mouret-Reynier, Marie-Ange; Durando, Xavier; Barthomeuf, Chantal; Chollet, Philippe

doi:10.4161/cbt.9.1.10392

Cited by 324 publications

(212 citation statements)

References 30 publications

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“…A phase I clinical trial conducted by Bayet-Robert et al suggested that the recommended dose of curcumin is 6 g/day for seven consecutive days every three weeks in combination with a standard dose of docetaxel in patients with advanced and metastatic breast cancer (61). A phase I clinical study conducted by Cheng et al in patients with high-risk or pre-malignant lesions concluded that curcumin is not toxic to humans up to 8 g/day when taken orally for 3 months (62).…”

Section: Resultsmentioning

confidence: 99%

Molecular Mechanisms of Anti-metastatic Activity of Curcumin

Deng

Verron

Rohanizadeh

2016

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Abstract. Cancer is the leading cause of death worldwide. Although cancer occurs as a localized disease, its morbidity and mortality rates remain high due to the ability of cancer cells to break-off from the primary tumor and spread to distant organs. Currently, chemotherapy is the main treatment for cancer; however, the increase in proportion of drug-resistant cancer cells and unpleasant side-effects of chemotherapy are still the major challenges in cancer therapy. Curcumin is a natural polyphenol compound and the main bioactive constituent of Indian spice turmeric, widely used in Indian and Chinese medicines. Curcumin has well-known therapeutic actions, including antiinflammatory, anti-microbial, anti-oxidant and anti-cancer properties. Curcumin induces cancer cell apoptosis through regulating various signaling pathways and arresting tumor cell cycle. Curcumin's therapeutic/ preventative actions on metastatic cancers have not been yet fully understood and studied. The present review explores the potential anti-metastatic mechanisms of curcumin, including inhibition of transcription factors and their signaling pathways (e.g., inflammatory cytokines (e.g., CXCL1, CXCL2, multiple proteases (e.g., uPA, MMPs), multiple protein kinases (e.g., MAPKs, FAK), regulation of miRNAs (e.g., miR21, miR181b) and heat shock proteins (HLJ1). In addition, possible synergistic actions of combination therapy of curcumin with current chemotherapies are discussed in this review.Despite all recent advances in oncology, cancer is still one of the deadliest diseases around the world (1). Cancer occurs as a localized disease but can spread to distant organs through migration, invasion and metastasis (2). Metastatic cancer is one of the major causes of death in cancer patients. Metastasis is a complex process involving multiple steps: (i) local migration through degrading basement membrane and extracellular matrix (ECM), (ii) intravasation into blood and/or lymphatic vessels, (iii) circulating to the target organ site, (iv) extravasation into target organ tissue and, finally, (v) multiplication in the target organ (2, 3). These steps are mediated by various factors, including growth factors, proteolysis degradation of extracellular matrix, cell-cell adhesion, cytoskeleton remodeling and changes of genes' expressions (2, 3). Metastasis is a non-random process that means each metastatic cancer type has its own preferred site of metastasis. For example, breast cancer cells preferentially metastasize to regional lymph nodes, liver, lungs and bone (4). Nowadays, there are different therapeutic approaches available for patients with metastatic cancers, including surgery, radiotherapy and chemotherapy. Chemotherapy remains the main treatment modality for cancer patients because of its ability of preventing invasion and metastasis. However, the morbidity and mortality rates in patients with metastatic cancer still remain high since current chemotherapy agents fail to selectively and effectively kill cancer cells without destroying normal ce...

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Section: Resultsmentioning

confidence: 99%

Molecular Mechanisms of Anti-metastatic Activity of Curcumin

Deng

Verron

Rohanizadeh

2016

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“…This open-label phase I trial included 14 patients with advanced or metastatic breast cancer. 41 The recommended peros dose of curcumin is 6000 mg per day for 7 consecutive days every 3 weeks in combination with a standard dose of docetaxel. According to the authors, it could be expected that a response rate up to 50% in a population of all evaluable patients treated with the combination of docetaxel/ curcumin.…”

Section: Pathological Bone Environmentmentioning

confidence: 99%

Therapeutic actions of curcumin in bone disorders

2016

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Curcumin is the active component of turmeric extract derived from the Curcuma longa plant. In the last decade, curcumin has raised a considerable interest in medicine owing to its negligible toxicity and multiple therapeutic actions including anti-cancer, anti-inflammatory and anti-microbial activities. Among the various molecular targets of curcumin, some are involved in bone remodeling, which strongly suggests that curcumin can affect the skeletal system. The review sheds light on the current and potential applications of curcumin to treat bone disorders characterized by an excessive resorption activity. Within the scope of this review, the novel formulations of curcumin to overcome its physico-chemical and pharmacokinetic constraints are also discussed.

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“…Curcumin was used in phase I clinical trial in combination with docetaxel and found to be tolerated in daily doses of up to 6 gms, in 14 women [45]. The authors concluded that some improvements were observed in biological and clinical responses to the treatment in most patients.…”

Section: Clinical Trials With Phytochemicalsmentioning

confidence: 99%