The effect of weight-based chemotherapy dosing in a cohort of gynecologic oncology patients

Hansen, Jean M.; Stephan, Jean-Marie; Freesmeier, Michele; Bender, David; Button, Anna M.; Goodheart, Michael J.

doi:10.1016/j.ygyno.2015.04.040

Cited by 8 publications

(8 citation statements)

References 22 publications

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“…Obesity is a significant issue, as >67% of US adults are overweight/obese (BMI >25), and 6% are morbidly obese (BMI >40) [11]. Drug metabolism and clearance are altered in obese individuals [12,13].…”

Section: Discussionmentioning

confidence: 99%

“…The impact of body size on adverse events and outcome has been reported in other solid tumors [12,25,42–51]. In one series using ABW-based dosing, grade three/four toxicities were significantly less common in obese versus normal weight patients, with comparable survival outcomes [42].…”

Section: Discussionmentioning

confidence: 99%

“…In a small cell lung cancer series treated with ABW-based doses, no significant differences in survival or toxicities were found by BMI [47]. Several gynecologic malignancy studies found no increased grade three/four toxicities with ABW-based dosing in obese patients [12,48]. Fully dosed obese patients with colorectal cancer had no more toxicities than those given reduced doses, with shorter survival in dose-reduced, versus fully-dosed, patients [49].…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

The impact of actual body weight-based chemotherapy dosing and body size on adverse events and outcome in older patients with breast cancer: Results from Cancer and Leukemia Group B (CALGB) trial 49907 (Alliance A151436)

Morrison

McCall

Muss

et al. 2018

Journal of Geriatric Oncology

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The impact of actual body weight-based chemotherapy dosing and body size on adverse events and outcome in older patients with breast cancer: Results from Cancer and Leukemia Group B (CALGB) trial 49907 (Alliance A151436)

Morrison

McCall

Muss

et al. 2018

Journal of Geriatric Oncology

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“…Alternative explanations include that the adipocytes within the bone marrow might mediate a non-specific protective effect by facilitating delayed drug release. In fact, obesity is associated with lower toxicity during chemotherapy for gynecological cancers in part due to the delayed drug release for drugs with high distribution volumes [ 34 , 35 ]. Within the bone marrow, increased adipocytic mass could thus possibly translate into a lower bolus dose but a longer exposition time upon chemotherapy, especially for chemotherapy agents with a high volume of distribution.…”

Section: Discussionmentioning

confidence: 99%

Correlation study between osteoporosis and hematopoiesis in the context of adjuvant chemotherapy for breast cancer

et al. 2017

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This retrospective study attempts to establish if a correlation exists between osteoporosis and hematopoiesis before and after adjuvant chemotherapy in the context of non-metastatic breast cancer. Osteoporosis is interpreted both as a direct marker of osteoblastic decline and as an indirect marker of increased bone marrow adiposity within the hematopoietic microenvironment. Patients from the “Centre du Sein” at CHUV (Centre Hospitalier Universitaire Vaudois) undergoing adjuvant chemotherapy were included in this study. Evolution of blood counts was studied in correlation with the osteoporosis status. Toxicity of chemotherapy was coded according to published probability of febrile neutropenia. One hundred forty-three women were included: mean age 52.1 ± 12.5 years, mean BMI (body mass index) 24.4 ± 4.1. BMD (bone mineral density) scored osteoporotic in 32% and osteopenic in 45%. Prior to chemotherapy, BMD was positively correlated with neutrophil (p < 0.001) and thrombocyte (p = 0.01) count; TBS (trabecular bone score) was not correlated with blood count. After the first cycle of chemotherapy, an increase of one point in TBS correlated with a decrease of 57% on the time to reach leucocyte nadir (p = 0.004). There was a positive correlation between BMD and risk of infection (p < 0.001). Our data demonstrates an association between osteoporosis and lower blood counts in a younger cohort than previously published, extending it for the first time to neutrophil counts in females. Our results suggest that the healthier the bone, the earlier the lowest leucocyte count value, prompting further research on this area.

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“…Additionally, endometrial cancer patients are often plagued by comorbidities such as obesity, diabetes mellitus, and hypertension, making novel therapies, which are frequently toxic, challenging to study. Only few treatment options are available for patients with advanced and recurrent endometrial cancer, and few novel drugs have been recently tested in clinical trial, with modest response rates 4 – 12 . One frequently used drug in endometrial cancer patients, especially those with metastatic lung lesions or who are deemed medically unfit for surgical management, is the progestin, megestrol acetate, which is associated with a 20-30% response rate in patients with advanced and recurring endometrial cancer 13 – 16 .…”

Section: Introductionmentioning

confidence: 99%

Pterostilbene, a natural phenolic compound, synergizes the antineoplastic effects of megestrol acetate in endometrial cancer

Wen

Lowe²,

Roberts

et al. 2017

Sci Rep

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Endometrial cancer is the most common gynecologic cancer in the United States and its incidence and mortality has been rising over the past decade. Few treatment options are available for patients with advanced and recurring endometrial cancers. Novel therapies, which are frequently toxic, are difficult to establish in this patient population which tends to be older and plagued by comorbidities such as diabetes mellitus and hypertension. Therefore, novel, non-toxic therapies are urgently needed. Megestrol acetate is a frequently used drug in endometrial cancer patients. However, its response rate is only 20–30%. To enhance the activity of megestrol acetate in endometrial cancer patients, we explored the potential of combining natural supplements with megestrol acetate and found that the addition of the natural phenolic compound, pterostilbene, to megestrol acetate resulted in a synergistic inhibition of cancer cell growth in vitro and an enhanced reduction of tumor growth in a xenograft mouse model. In addition, dual treatment led to attenuation of signaling pathways, as well as cell cycle and survival pathways. Our results demonstrated for the first time that the anti-tumor activity of megestrol acetate can be enhanced by combining with pterostilbene, providing an insight into the potential application of pterostilbene and megestrol acetate combination for the treatment of endometrial cancer.

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The effect of weight-based chemotherapy dosing in a cohort of gynecologic oncology patients

Cited by 8 publications

References 22 publications

The impact of actual body weight-based chemotherapy dosing and body size on adverse events and outcome in older patients with breast cancer: Results from Cancer and Leukemia Group B (CALGB) trial 49907 (Alliance A151436)

The impact of actual body weight-based chemotherapy dosing and body size on adverse events and outcome in older patients with breast cancer: Results from Cancer and Leukemia Group B (CALGB) trial 49907 (Alliance A151436)

Correlation study between osteoporosis and hematopoiesis in the context of adjuvant chemotherapy for breast cancer

Pterostilbene, a natural phenolic compound, synergizes the antineoplastic effects of megestrol acetate in endometrial cancer

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