A phase 1 dose-escalation study on the safety, tolerability and activity of liposomal curcumin (Lipocurc™) in patients with locally advanced or metastatic cancer

Purpose This study was conducted to investigate the safety and tolerability of increasing doses of liposomal curcumin in patients with metastatic cancer. Investigations of anti-tumor activity and of the pharmacokinetics of curcumin were secondary objectives. Methods In this phase I, single-center, o...

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Vydáno v:Cancer chemotherapy and pharmacology Ročník 82; číslo 4; s. 695 - 706
Hlavní autoři: Greil, Richard, Greil-Ressler, Sigrun, Weiss, Lukas, Schönlieb, Charlotte, Magnes, Teresa, Radl, Bianca, Bolger, Gordon T., Vcelar, Brigitta, Sordillo, Peter P.
Médium: Journal Article
Jazyk:angličtina
Vydáno: Berlin/Heidelberg Springer Berlin Heidelberg 01.10.2018
Springer Nature B.V
Témata:
Adult
Aged
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - adverse effects
Antineoplastic Agents - pharmacokinetics
Antitumor agents
Cancer
Cancer Research
Clinical trials
Colonic Neoplasms - drug therapy
Colonic Neoplasms - pathology
Colorectal cancer
Curcumin
Curcumin - administration & dosage
Curcumin - adverse effects
Curcumin - pharmacokinetics
Dose-Response Relationship, Drug
Drug Monitoring - methods
Drug Tolerance
Drug-Related Side Effects and Adverse Reactions - blood
Drug-Related Side Effects and Adverse Reactions - diagnosis
Drug-Related Side Effects and Adverse Reactions - etiology
Female
Hemoglobin
Hemoglobins - analysis
Hemolysis
Hemolysis - drug effects
Humans
Intravenous administration
Male
Medicine
Medicine & Public Health
Metastases
Metastasis
Middle Aged
Neoplasm Invasiveness
Neoplasm Metastasis - drug therapy
Neoplasm Metastasis - pathology
Neoplasm Staging
Oncology
Original
Original Article
Pharmacokinetics
Pharmacology/Toxicology
Prostate cancer
Prostatic Neoplasms - drug therapy
Prostatic Neoplasms - pathology
Toxicity
Treatment Outcome
Tumor markers
Tumors
Hemolysis
Prostate carcinoma
Curcumin
Phase I cancer trials
Colon carcinoma
Lipocurc
ISSN:0344-5704, 1432-0843, 1432-0843
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Shrnutí:Purpose This study was conducted to investigate the safety and tolerability of increasing doses of liposomal curcumin in patients with metastatic cancer. Investigations of anti-tumor activity and of the pharmacokinetics of curcumin were secondary objectives. Methods In this phase I, single-center, open-label study in patients with metastatic tumors, liposomal curcumin was administered as a weekly intravenous infusion for 8 weeks. Dose escalation was started at 100 mg/m 2 over 8 h and the dose increased to 300 mg/m 2 over 6 h. Results 32 patients were treated. No dose-limiting toxicity was observed in 26 patients at doses between 100 and 300 mg/m 2 over 8 h. Of six patients receiving 300 mg/m 2 over 6 h, one patient developed hemolysis, and three other patients experienced hemoglobin decreases > 2 g/dL without signs of hemolysis. Pharmacokinetic analyses revealed stable curcumin plasma concentrations during infusion followed by rapid declines to undetectable levels after the infusion. Anti-tumor activity by RECIST V1.1 was not detected. Significant tumor marker responses and transient clinical benefit were observed in two patients. Conclusion 300 mg/m 2 liposomal curcumin over 6 h was the maximum tolerated dose in these heavily pretreated patients, and is the recommended starting dose for anti-cancer trials.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:0344-5704
1432-0843
1432-0843
DOI:10.1007/s00280-018-3654-0