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 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 2/2012

01-11-2012 | Review

Effect of obesity on toxicity in women treated with adjuvant chemotherapy for early-stage breast cancer: a systematic review

Authors: James Carroll, Melinda Protani, Euan Walpole, Jennifer H. Martin

Published in: Breast Cancer Research and Treatment | Issue 2/2012

Login to get access

Abstract

The purpose of this study is to provide more definite evidence regarding the role of dose modification of chemotherapy in obese women with breast cancer by systematically reviewing current literature regarding chemotherapy-induced toxicity rates in obese and non-obese women with early-stage breast cancer. A systematic search of Pubmed and EMBASE was conducted to identify original studies investigating chemotherapy-induced toxicity in obese women receiving adjuvant chemotherapy treatment for breast cancer. Ten studies were identified. We noted low rates of adjustment for confounders such as prophylactic hematopoietic growth factor use and empirical dose reductions. Seven studies found reduced toxicity in obese compared to non-obese women. Of four studies, where dose capping was precluded or statistically adjusted for, three found reduced toxicity in obese women. These outcomes include less febrile neutropenia (body mass index (BMI) >23.6; odds ratio (OR) 4.4; 95 % confidence interval (CI) 1.65–12.01), fewer hospital admissions (BMI >35; OR 0.61, 95 % CI 0.38–0.97), and fewer neutropenic events (BMI >25; OR 0.49; 95 % CI 0.37–0.66). Only a single study reported higher rates of toxicity in obese women, but this study had significant methodological issues. As a conclusion, we observed that obese patients tolerate chemotherapy better than lean patients. However, this may be confounded by poorly specified dose capping practices and the use of hematopoietic growth factors. Further research should focus on improved documentation of body size, of dose, and of use of growth factors, and analysis of how these affect recurrence rates, toxicity, and survival.
Literature
1.
Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M (2008) Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 371(9612):569–578PubMedCrossRef
2.
Protani M, Coory M, Martin JH (2010) Effect of obesity on survival of women with breast cancer: systematic review and meta-analysis. Breast Cancer Res Treat 123(3):627–635PubMedCrossRef
3.
Hanley MJ, Abernethy DR, Greenblatt DJ (2010) Effect of obesity on the pharmacokinetics of drugs in humans. Clin Pharmacokinet 49(2):71–87PubMedCrossRef
4.
Barpe DR, Rosa DD, Froehlich PE (2010) Pharmacokinetic evaluation of doxorubicin plasma levels in normal and overweight patients with breast cancer and simulation of dose adjustment by different indexes of body mass. Eur J Pharm Sci 41(3–4):458–463PubMedCrossRef
5.
Gusella M, Toso S, Ferrazzi E, Ferrari M, Padrini R (2002) Relationships between body composition parameters and fluorouracil pharmacokinetics. Br J Clin Pharmacol 54(2):131–139PubMedCrossRef
6.
Prado CM, Baracos VE, McCargar LJ, Mourtzakis M, Mulder KE, Reiman T, Butts CA, Scarfe AG, Sawyer MB (2007) Body composition as an independent determinant of 5-fluorouracil-based chemotherapy toxicity. Clin Cancer Res 13(11):3264–3268PubMedCrossRef
7.
Sparreboom A, Wolff AC, Mathijssen RHJ, Chatelut E, Rowinsky EK, Verweij J, Baker SD (2007) Evaluation of alternate size descriptors for dose calculation of anticancer drugs in the obese. J Clin Oncol 25(30):4707–4713PubMedCrossRef
8.
Hunter RJ, Navo MA, Thaker PH, Bodurka DC, Wolf JK, Smith JA (2009) Dosing chemotherapy in obese patients: Actual versus assigned body surface area (BSA). Cancer Treat Rev 35(1):69–78PubMedCrossRef
9.
Thompson LA, Lawson AP, Sutphin SD, Steinke D, Adams VR (2010) Description of current practices of empiric chemotherapy dose adjustment in obese adult patients. J Oncol Pract 6(3):141–145PubMedCrossRef
10.
Field KM, Kosmider S, Jefford M, Michael M, Jennens R, Green M, Gibbs P (2008) Chemotherapy dosing strategies in the obese, elderly, and thin patient: results of a nationwide survey. J Oncol Pract 4(3):108–113PubMedCrossRef
11.
Greenman CG, Jagielski CH, Griggs JJ (2008) Breast cancer adjuvant chemotherapy dosing in obese patients: dissemination of information from clinical trials to clinical practice. Cancer 112(10):2159–2165PubMedCrossRef
12.
Cheymol G (2000) Effects of obesity on pharmacokinetics implications for drug therapy. Clin Pharmacokinet 39(3):215–231PubMedCrossRef
13.
Bonadonna G, Valagussa P (1981) Dose-response effect of adjuvant chemotherapy in breast cancer. N Engl J Med 304(1):10–15PubMedCrossRef
14.
Griggs JJ, Mangu PB, Anderson H, Balaban EP, Dignam JJ, Hryniuk WM, Morrison VA, Pini TM, Runowicz CD, Rosner GL 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):1553–61
15.
Crawford J, Dale DC, Lyman GH (2004) Chemotherapy-induced neutropenia-risks, consequences, and new directions for its management. Cancer 100(2):228–237PubMedCrossRef
16.
Wood WC, Budman DR, Korzun AH, Cooper MR, Younger J, Hart RD, Moore A, Ellerton JA, Norton L, Ferree CR et al (1994) Dose and dose intensity of adjuvant chemotehrapy for stage-II, node-positive breast-carcinoma. N Engl J Med 330(18):1253–1259PubMedCrossRef
17.
Schwenkglenks M, Pettengell R, Jackisch C, Paridaens R, Constenla M, Bosly A, Szucs TD, Leonard R (2011) Risk factors for chemotherapy-induced neutropenia occurrence in breast cancer patients: data from the INC-EU prospective observational European neutropenia study. Support Care Cancer 19(4):483–490PubMedCrossRef
18.
Chan A, Chen C, Chiang J, Tan SH, Ng R (2011) Incidence of febrile neutropenia among early-stage breast cancer patients receiving anthracycline-based chemotherapy. Support Care Cancer. 20(7):1525–32
19.
de Azambuja E, McCaskill-Stevens W, Francis P, Quinaux E, Crown JP, Vicente M, Giuliani R, Nordenskjold B, Gutierez J, Andersson M et al (2010) The effect of body mass index on overall and disease-free survival in node-positive breast cancer patients treated with docetaxel and doxorubicin-containing adjuvant chemotherapy: the experience of the BIG 02–98 trial. Breast Cancer Res Treat 119(1):145–153PubMedCrossRef
20.
Gianni L, Cole BF, Panzini I, Snyder R, Holmberg SB, Byrne M, Crivellari D, Colleoni M, Aebi S, Simoncini E et al (2008) Anemia during adjuvant non-taxane chemotherapy for early breast cancer: Incidence and risk factors from two trials of the International Breast Cancer Study Group. Support Care Cancer 16(1):67–74PubMedCrossRef
21.
Griggs JJ, Sorbero ME, Lyman GH (2005) Undertreatment of obese women receiving breast cancer chemotherapy. Arch Intern Med 165(11):1267–1273PubMedCrossRef
22.
Han HS, Reis IM, Zhao W, Kuroi K, Toi M, Suzuki E, Syme R, Chow L, Yip AY, Gluck S (2011) Racial differences in acute toxicities of neoadjuvant or adjuvant chemotherapy in patients with early-stage breast cancer. Eur J Cancer 47(17):2537–2545
23.
Jenkins P, Elyan S, Freeman S (2007) Obesity is not associated with increased myelosuppression in patients receiving chemotherapy for breast cancer. Eur J Cancer 43(3):544–548PubMedCrossRef
24.
Poikonen P, Blomqvist C, Joensuu H (2001) Effect of obesity on the leukocyte nadir in women treated with adjuvant cyclophosphamide, methotrexate, and fluorouracil dosed according to body surface area. Acta Oncol 40(1):67–71PubMedCrossRef
25.
Rosner GL, Hargis JB, Hollis DR, Budman DR, Weiss RB, Henderson IC, Schilsky RL (1996) Relationship between toxicity and obesity in women receiving adjuvant chemotherapy for breast cancer: results from cancer and leukemia Group B study 8541. J Clin Oncol 14(11):3000–3008PubMed
26.
Schwenkglenks M, Jackisch C, Constenla M, Kerger JN, Paridaens R, Auerbach L, Bosly A, Pettengell R, Szucs TD, Leonard R (2006) Neutropenic event risk and impaired chemotherapy delivery in six European audits of breast cancer treatment. Support Care Cancer 14(9):901–909PubMedCrossRef
27.
NCI (2010) Common Terminology Criteria for Adverse Events Version 4.03. In. Edited by Institute NC: National Cancer Institute
28.
Saarto T, Blomqvist C, Rissanen P, Auvinen A, Elomaa I (1997) Haematological toxicity: A marker of adjuvant chemotherapy efficacy in stage II and III breast cancer. Br J Cancer 75(2):301–305PubMedCrossRef
29.
Brosteanu O, Hasenclever D, Loeffler M, Diehl V (2004) Low acute hematological toxicity during chemotherapy predicts reduced disease control in advanced Hodgkin’s disease. Ann Hematol 83(3):176–182PubMedCrossRef
30.
Meyerhardt JA, Catalano PJ, Haller DG, Mayer RJ, Benson AB 3rd, Macdonald JS, Fuchs CS (2003) Influence of body mass index on outcomes and treatment-related toxicity in patients with colon carcinoma. Cancer 98(3):484–495PubMedCrossRef
31.
Dignam JJ, Polite BN, Yothers G, Raich P, Colangelo L, O’Connell MJ, Wolmark N (2006) Body mass index and outcomes in patients who receive adjuvant chemotherapy for colon cancer. J Natl Cancer Inst 98(22):1647–1654PubMedCrossRef
32.
Lopes-Serrao MD, Ussery SM, Hall RG 2nd, Shah SR (2011) Evaluation of chemotherapy-induced severe myelosuppression incidence in obese patients with capped dosing. J Oncol Pract 7(1):13–17PubMedCrossRef
33.
Kizer NT, Thaker PH, Gao F, Zighelboim I, Powell MA, Rader JS, Mutch DG, Grigsby PW (2011) The effects of body mass index on complications and survival outcomes in patients with cervical carcinoma undergoing curative chemoradiation therapy. Cancer 117(5):948–956PubMedCrossRef
34.
Meyerhardt JA, Tepper JE, Niedzwiecki D, Hollis DR, McCollum AD, Brady D, O’Connell MJ, Mayer RJ, Cummings B, Willett C et al (2004) Impact of body mass index on outcomes and treatment-related toxicity in patients with stage II and III rectal cancer: findings from Intergroup Trial 0114. J Clin Oncol 22(4):648–657PubMedCrossRef
35.
Pettengell R, Bosly A, Szucs TD, Jackisch C, Leonard R, Paridaens R, Constenla M, Schwenkglenks M (2009) Multivariate analysis of febrile neutropenia occurrence in patients with non-Hodgkin lymphoma: data from the INC-EU prospective observational European neutropenia study. Br J Haematol 144(5):677–685PubMedCrossRef
36.
Wright JD, Tian C, Mutch DG, Herzog TJ, Nagao S, Fujiwara K, Powell MA (2008) Carboplatin dosing in obese women with ovarian cancer: a Gynecologic Oncology Group study. Gynecol Oncol 109(3):353–358PubMedCrossRef
37.
Modesitt SC, Tian C, Kryscio R, Thigpen JT, Randall ME, Gallion HH, Fleming GF (2007) Impact of body mass index on treatment outcomes in endometrial cancer patients receiving doxorubicin and cisplatin: a Gynecologic Oncology Group study. Gynecol Oncol 105(1):59–65PubMedCrossRef
38.
Lind MJ, Margison JM, Cerny T, Thatcher N, Wilkinson PM (1989) Prolongation of ifosfamide elimination half-life in obese patients due to altered drug distribution. Cancer Chemother Pharmacol 25(2):139–142PubMedCrossRef
39.
Overweight and obesity in adults (2008). In. Canberra: Australian Bureau of Stastics
40.
Powis G, Reece P, Ahmann DL, Ingle JN (1987) Effect of body weight on the pharmacokinetics of cyclophosphamide in breast cancer patients. Cancer Chemother Pharmacol 20(3):219–222PubMedCrossRef
41.
Rodvold KA, Rushing DA, Tewksbury DA (1988) Doxorubicin clearance in the obese. J Clin Oncol 6(8):1321–1327PubMed
42.
Jones LW, Haykowsky M, Peddle CJ, Joy AA, Pituskin EN, Tkachuk LM, Courneya KS, Slamon DJ, Mackey JR (2007) Cardiovascular risk profile of patients with HER2/neu-positive breast cancer treated with anthracycline-taxane-containing adjuvant chemotherapy and/or trastuzumab. Cancer Epidemiol Biomark Prev 16(5):1026–1031CrossRef
43.
Fumoleau P, Roche H, Kerbrat P, Bonneterre J, Romestaing P, Fargeot P, Namer M, Monnier A, Montcuquet P, Goudier MJ et al (2006) Long-term cardiac toxicity after adjuvant epirubicin-based chemotherapy in early breast cancer: French Adjuvant Study Group results. Ann Oncol 17(1):85–92PubMedCrossRef
Metadata
Title
Effect of obesity on toxicity in women treated with adjuvant chemotherapy for early-stage breast cancer: a systematic review
Authors
James Carroll
Melinda Protani
Euan Walpole
Jennifer H. Martin
Publication date
01-11-2012
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 2/2012
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-012-2213-3

Other articles of this Issue 2/2012

Breast Cancer Research and Treatment 2/2012 Go to the issue

Review

Role of epidermal growth factor receptor in breast cancer

Preclinical Study

Investigation of elemene-induced reversal of tamoxifen resistance in MCF-7 cells through oestrogen receptor α (ERα) re-expression

Clinical Trial

Fulvestrant 500 mg versus anastrozole 1 mg for the first-line treatment of advanced breast cancer: follow-up analysis from the randomized ‘FIRST’ study

Epidemiology

A prognostic model of early breast cancer relapse after standard adjuvant therapy and comparison with metastatic disease on initial presentation

Epidemiology

Explaining age-related differences in depression following breast cancer diagnosis and treatment

Erratum

Erratum to: Comparison of relative versus absolute arm size change as criteria for quantifying breast cancer-related lymphedema: the flaws in current studies and need for universal methodology
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