Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 1/2019

01-01-2019 | Original Article

Mononuclear phagocyte system function and nanoparticle pharmacology in obese and normal weight ovarian and endometrial cancer patients

Authors: Brittney R. Starling, Parag Kumar, Andrew T. Lucas, David Barrow, Laura Farnan, Laura Hendrix, Hugh Giovinazzo, Gina Song, Paola Gehrig, Jeannette T. Bensen, William C. Zamboni

Published in: Cancer Chemotherapy and Pharmacology | Issue 1/2019

Login to get access

Abstract

Purpose

Obesity may alter mononuclear phagocyte system (MPS) function and the pharmacology and efficacy of nanoparticles therapies, such as PEGylated liposomal doxorubicin (PLD). We aimed to evaluate the relationships between hormone and chemokine mediators of MPS function and the pharmacokinetic (PK) exposure of PLD in obese and normal weight patients with ovarian and endometrial cancer.

Methods

Hormone and chemokine mediators in obese and normal weight ovarian and endometrial cancer patients were measured. A separate pharmacology study was performed that evaluated the relationship between serum hormone concentrations, MPS function, and PK disposition of PLD in refractory ovarian cancer patients.

Results

Univariate analysis revealed a significant relationship between serum estradiol and body mass index (OR 8.64, 95% CI 2.67–28.0, p < 0.001). Estrone and testosterone concentrations were positively correlated with MPS function (ρ = 0.57 and 0.53, p = 0.14 and 0.18, respectively) and inversely correlated with PLD PK exposure (ρ = − 0.75 and − 0.76, respectively, p = 0.02 for both).

Conclusions

Higher MPS function resulting in reduced PLD exposure is a potential mechanism for reduced efficacy of PLD and other nanoparticles observed in obese patients with cancer. PK simulations suggest higher doses of PLD are required in obese patients to achieve similar exposures as standard dosing in normal weight patients.
Literature
1.
Farokhzad OC, Langer R (2009) Impact of nanotechnology on drug delivery. ACS Nano 3(1):16–20CrossRef
2.
Peer D, Karp JM, Hong S et al (2007) Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol 2(12):751–760CrossRef
3.
Maeda H, Wu J, Sawa T, Matsumura Y et al (2000) Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Control Release 65(1–2):271–284CrossRef
4.
Zamboni WC (2008) Concept and clinical evaluation of carrier-mediated anticancer agents. Oncologist 13(3):248–260CrossRef
5.
Schell RF, Sidone BJ, Caron WP et al (2014) Meta-analysis of inter-patient pharmacokinetic variability of liposomal and non-liposomal anticancer agents. Nanomed Nanotechnol Biol Med 10(1):109–117CrossRef
6.
Song G, Wu H, Yoshino K et al (2012) Factors affecting the pharmacokinetics and pharmacodynamics of liposomal drugs. J Liposome Res 22(3):177–192CrossRef
7.
Caron WP, Song G, Kumar P et al (2012) Interpatient pharmacokinetic and pharmacodynamic variability of carrier-mediated anticancer agents. Clin Pharmacol Ther 91(5):802–812CrossRef
8.
Wu H, Ramanathan RK, Zamboni BA et al (2011) Population pharmacokinetics of pegylated liposomal CKD-602 (S-CKD602) in patients With advanced malignancies. J Clin Pharmacol 52(2):180–194CrossRef
9.
Hume DA (2006) The mononuclear phagocyte system. Curr Opin Immunol 18(1):49–53CrossRef
10.
Moghimi SM, Murray JC, Hunter AC (2001) Long-circulating and target specific nanoparticles: theory to practice. Pharmacol Rev 53(2):283–318PubMed
11.
Calle EE, Rodriguez C, Walker-Thurmond K et al (2003) Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med 348(17):1625–1638CrossRef
12.
Song G, Tarrant TK, White TF et al (2015) Roles of chemokines CCL2 and CCL5 in the pharmacokinetics of PEGylated liposomal doxorubicin in vivo and in patients with recurrent epithelial ovarian cancer. Nanomed Nanotechnol Biol Med 11(7):1797–1807CrossRef
13.
Zamboni WC, Strychor S, Joseph E et al (2007) Plasma, tumor, and tissue disposition of STEALTH liposomal CKD-602 (S-CKD602) and nonliposomal CKD-602 in mice bearing A375 human melanoma xenografts. Clin Cancer Res 13(23):7217–7223CrossRef
14.
Song G, Moore S, Tarrant T et al (2012) Relationship between complement factors and CC chemokines and the pharmacokinetics (PK) and pharmacodynamics (PD) of PEGylated liposomal doxorubicin (Doxil) in patients with refractory epithelial ovarian cancer (EOC). In: Proceedings of 24th EORTC-NCI-AACR symposium on “molecular targets and cancer therapeutics. Abstract 126. https://​doi.​org/​10.​1016/​S0959-8049(12)71924-X
15.
Zamboni WC, Strychor S, Maruca L et al (2009) Pharmacokinetic study of pegylated liposomal CKD-602 (S-CKD602) in patients with advanced malignancies. Clin Pharmacol Ther 86(5):519–526CrossRef
16.
Wu H, Infante JR, Keedy VL et al (2015) Factors affecting the pharmacokinetics and pharmacodynamics of PEGylated liposomal irinotecan (IHL-305) in patients with advanced solid tumors. Int J Nanomed 10:1201–1209CrossRef
17.
Nielsen H (1984) Effect of cis-platinum on human blood monocyte function in vitro. Cancer Immunol Immunother 18(3):223–225CrossRef
18.
Nicol T, Bilbey D, Charles L et al (1964) Oestrogen: the natural stimulant of body defence. J Endocrinol 30:277–291CrossRef
19.
Chao TC, Phuangsab A, Van Alten PJ et al (1996) Steroid sex hormones and macrophage function: regulation of chemiluminescence and phagocytosis. Am J Reprod Immunol 35(2):106–113CrossRef
20.
Vernon-Roberts B (1969) The effects of steroid hormones on macrophage activity. Int Rev Cytol 25:131–159CrossRef
21.
22.
Cleary MP, Grossmann ME (2009) Minireview: obesity and breast cancer: the estrogen connection. Endocrinology 150(6):2537–2542CrossRef
23.
Connolly BS, Barnett C, Vogt KN et al (2002) A meta-analysis of published literature on waist-to-hip ratio and risk of breast cancer. Nutr Cancer 44(2):127–138CrossRef
24.
Harvie M, Hooper L, Howell AH (2003) Central obesity and breast cancer risk: a systematic review. Obes Rev 4(3):157–173CrossRef
25.
Johnson AR, Justin Milner J, Makowski L (2012) The inflammation highway: metabolism accelerates inflammatory traffic in obesity. Immunol Rev 249(1):218–238CrossRef
26.
Flegal KM, Carroll MD, Ogden CL et al (2010) Prevalence and trends in obesity among US adults, 1999–2008. JAMA 303(3):235–241CrossRef
27.
Harris MI, Klein R, Welborn TA et al (1992) Onset of NIDDM occurs at least 4–7 year before clinical diagnosis. Diabetes Care 15(7):815–819CrossRef
28.
Jemal A, Siegel R, Xu J, Ward E (2010) Cancer statistics, 2010. CA Cancer J Clin 60(5):277–300CrossRef
29.
Steiner E, Plata K, Interthal C et al (2007) Diabetes mellitus is a multivariate independent prognostic factor in endometrial carcinoma: a clinicopathologic study on 313 patients. Eur J Gynaecol Oncol 28(2):95–97PubMed
30.
Reed MJ, Cheng RW, Noel CT et al (1983) Plasma levels of estrone, estrone sulfate, and estradiol and the percentage of unbound estradiol in postmenopausal women with and without breast disease. Cancer Res 43(8):3940–3943PubMed
31.
Hankinson SE, Manson JE, Willett WC et al (1995) Reproducibility of plasma hormone levels in postmenopausal women over a 2–3-year period. Cancer Epidemiol Biomark Prev 4(6):649–654
32.
Andreopoulou E, Gaiotti D, Kim E et al (2007) Pegylated liposomal doxorubicin HCL (PLD; Caelyx/Doxil): experience with long-term maintenance in responding patients with recurrent epithelial ovarian cancer. Ann Oncol 18(4):716–721CrossRef
33.
Muggia FM, Blessing JA, Sorosky J et al (2002) Phase II trial of the pegylated liposomal doxorubicin in previously treated metastatic endometrial cancer: a gynecologic oncology group study. J Clin Oncol 20(9):2360–2364CrossRef
34.
Gadducci A, Cosio S, Genazzani AR (2006) Old and new perspectives in the pharmacological treatment of advanced or recurrent endometrial cancer: hormonal therapy, chemotherapy and molecularly targeted therapies. Crit Rev Oncol Hematol 58(3):242–256CrossRef
35.
Gray DS, Fujioka K (1991) Use of relative weight and Body Mass Index for the determination of adiposity. J Clin Epidemiol 44(6):545–550CrossRef
36.
37.
Caron WP, Lay JC, Fong AM et al (2013) Translational studies of phenotypic probes for the mononuclear phagocyte system and liposomal pharmacology. J Pharmacol Exp Ther 347:599–606CrossRef
38.
Demark-Wahnefried W, Platz EA, Ligibel JA et al (2012) The role of obesity in cancer survival and recurrence. Cancer Epidemiol Biomark Prev Publ Am Assoc Cancer Res Cospons Am Soc Prev Oncol 21(8):1244–1259CrossRef
39.
La-Beck NM, Zamboni BA, Gabizon A et al (2012) Factors affecting the pharmacokinetics of pegylated liposomal doxorubicin in patients. Cancer Chemother Pharmacol 69(1):43–50CrossRef
40.
Song G, Terrant TK, Barrow DA et al (2012) The effect of CC chemokine ligand-2 (CCL2/MCP-1) and CC chemokine ligand-5 (CCL5/RANTES) on the pharmacokinetics (PK) and pharmacodynamics (PD) of PEGylated liposomal CKD-602 (S-CKD602) in patients with advanced solid tumors. In: Proceedings of American association for cancer research. Abstract 754. https://​doi.​org/​10.​1158/​1538-7445.​AM2012-754
41.
Li J, Papadopoulos V, Vihma V (2015) Steroid biosynthesis in adipose tissue. Steroids 103:89–104CrossRef
42.
Giovinazzo H, Kumar P, Sheikh A et al (2016) Technetium Tc 99 m sulfur colloid phenotypic probe for the pharmacokinetics and pharmacodynamics of PEGylated liposomal doxorubicin in women with ovarian cancer. Cancer Chemother Pharmacol 77(3):565–573CrossRef
43.
Gordon AN, Tonda M, Sun S et al (2004) Long-term survival advantage for women treated with pegylated liposomal doxorubicin compared with topotecan in a phase 3 randomized study of recurrent and refractory epithelial ovarian cancer. Gynecol Oncol 95(1):1–8CrossRef
44.
Homesley HD, Blessing JA, Sorosky J et al (2005) Phase II trial of liposomal doxorubicin at 40 mg/m(2) every 4 weeks in endometrial carcinoma: a Gynecologic Oncology Group Study. Gynecol Oncol 98(2):294–298CrossRef
45.
Griggs JJ, Mangu PB, Temin S et al (2012) Appropriate chemotherapy dosing for obese adult patients with cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol 30(13):1553–1561CrossRef
Metadata
Title
Mononuclear phagocyte system function and nanoparticle pharmacology in obese and normal weight ovarian and endometrial cancer patients
Authors
Brittney R. Starling
Parag Kumar
Andrew T. Lucas
David Barrow
Laura Farnan
Laura Hendrix
Hugh Giovinazzo
Gina Song
Paola Gehrig
Jeannette T. Bensen
William C. Zamboni
Publication date
01-01-2019
Publisher
Springer Berlin Heidelberg
Published in
Cancer Chemotherapy and Pharmacology / Issue 1/2019
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-018-3702-9

Other articles of this Issue 1/2019

Cancer Chemotherapy and Pharmacology 1/2019 Go to the issue

Original Article

Clinical and in vitro studies of the correlation between MGMT and the effect of streptozocin in pancreatic NET

Original Article

Oral administration of irinotecan in patients with solid tumors: an open-label, phase I, dose escalating study evaluating safety, tolerability and pharmacokinetics

Original Article

Safety of intraperitoneal paclitaxel combined with conventional chemotherapy for colorectal cancer with peritoneal carcinomatosis: a phase I trial

Short Communication

Lack of UGT polymorphism association with idasanutlin pharmacokinetics in solid tumor patients

Original Article

Regorafenib or rechallenge chemotherapy: which is more effective in the third-line treatment of metastatic colorectal cancer?

Original Article

Associations among regorafenib concentrations, severe adverse reactions, and ABCG2 and OATP1B1 polymorphisms
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits