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)

PURPOSE We examined data from a large clinical trial to determine if chemotherapy dosing according to actual body weight places obese patients at greater risk of toxicity. PATIENTS AND METHODS Cancer and Leukemia Group B (CALGB) study 8541, a randomized study of schedule and dose of adjuvant cyclophosphamide, doxorubicin, and fluorouracil (CAF) for stage II breast cancer patients with positive regional lymph nodes, provided data on 1,435 women for analysis. Using body-mass index (BMI), we classified a woman as obese if her BMI was > or = 27.3 kg/m2; doses were considered weight-based if within 5% of values calculated using actual weight. Our primary analysis concerned toxicity risks during cycle 1. RESULTS Among women who received weight-based doses of the most dose-intensive CAF regimen, 47% of obese and 51% of nonobese women experienced severe hematologic toxicity (grade > or = 3) during cycle 1 (P = .51, two-tailed). The overall risk ratio (obese v nonobese) of treatment failure among women who received weight-based doses during cycle 1 was 1.02 (95% confidence interval, 0.83 to 1.26), stratified by treatment and adjusted for number of positive nodes, menopausal status, hormone receptor status, and tumor size. The overall adjusted failure risk ratio (weight-based v reduced initial doses) was 0.73 (95% confidence interval, 0.53 to 1.00) among obese women. CONCLUSION Obese patients initially dosed (within 5%) by actual weight did not experience excess cycle 1 toxicity or worse outcome compared with nonobese women dosed similarly. The data suggest that obese women who received reduced doses in cycle 1 experienced worse failure-free survival. We recommend that initial doses of CAF be computed according to actual body weight.

Download Full-text

Impact of weight and creatinine measurements in carboplatin dosing.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e13027 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e13027-e13027 ◽

Cited By ~ 1

Author(s):

Feriel Boumedien ◽

Youri Arsenault ◽

Nathalie LeTarte

Keyword(s):

Body Weight ◽

Serum Creatinine ◽

Actual Body ◽

Retrospective Chart Review ◽

Actual Body Weight ◽

Calculated Dose ◽

The Difference ◽

The Impact ◽

Carboplatin Dose ◽

Creatinine Measurement

e13027 Background: Controversy surrounding weight in Carboplatin dosing is still current. Also, new methods of measuring serum creatinine have raised more questions regarding the precision of Carboplatin dose calculations. The two objectives of this study were to evaluate the impact of alternative weight indicators (actual and adjusted body weight) in the Cockcroft–Gault equation and the use of different creatinine measurements (standard and IDMS) in order to accurately predict Carboplatin dose. Methods: We performed a retrospective chart review on all patients who received at least one dose of Carboplatin between March 7th and May 8th 2010. The patients were divided into two groups according to their body mass index (BMI): 20 < BMI < 27 and BMI ≥ 27. The differential creatinine clearance and Carboplatin dose were assessed in each group using the actual body weight and the adjusted body weight with IDMS creatinine. Moreover, for patients who had their creatinine measurement at the CHUM hospital, we calculate the difference in Carboplatin dose by using the standard creatinine (SC) measurement and IDMS creatinine with the same weight. Results: A total of 95 patients, representing 119 Carboplatin doses, were included in the analysis. 82% were women and median age was 63. The average BMI was 26,6. The Carboplatin expected AUC was 5 for 89% of patients and Carboplatin was associated to Paclitaxel in 78% of patients. In patients with a 20<BMI< 27 (44%), the average difference between the calculated dose using their actual body weight and adjusted body weight was +6.03% (95% CI, 5.2 to 6.9%). For patients with a BMI ≥ 27 (43%), the mean dose difference was +20.6% (95% CI, 18.8 to 22.5%). The use of SC or IDMS creatinine led to a discrepancy in doses of 5.2% (95% CI, 4.7 to 5.7%) for patients with BMI <27 (35 patients) and 5.5% (95% CI, 4.9 to 6.2%) for those with BMI ≥ 27 (23 patients). Conclusions: Based on these findings, we decide in our clinic, to use the actual body weight for patients with a BMI between 20 and 27, and the adjusted body weight for those with a BMI ≥ 27. We also chose not to modify our doses based on the type of the serum creatinine measurement.

Download Full-text

Quality of Life of Older Patients With Early-Stage Breast Cancer Receiving Adjuvant Chemotherapy: A Companion Study to Cancer and Leukemia Group B 49907

Journal of Clinical Oncology ◽

10.1200/jco.2010.29.9859 ◽

2011 ◽

Vol 29 (8) ◽

pp. 1022-1028 ◽

Cited By ~ 38

Author(s):

Alice B. Kornblith ◽

Lan Lan ◽

Laura Archer ◽

Ann Partridge ◽

Gretchen Kimmick ◽

...

Keyword(s):

Breast Cancer ◽

Quality Of Life ◽

Older Patients ◽

Standard Treatment ◽

Early Stage ◽

Early Stage Breast Cancer ◽

Standard Chemotherapy ◽

Group B ◽

Leukemia Group

Purpose A phase III trial (Cancer and Leukemia Group B CALGB-49907) was conducted to test whether older patients with early-stage breast cancer would have equivalent relapse-free and overall survival with capecitabine compared with standard chemotherapy. The quality of life (QoL) substudy tested whether capecitabine treatment would be associated with a better QoL than standard chemotherapy. Patients and Methods QoL was assessed in 350 patients randomly assigned to either standard chemotherapy (cyclophosphamide, methotrexate, and fluorouracil [CMF] or doxorubicin and cyclophosphamide [AC]; n = 182) or capecitabine (n = 168). Patients were interviewed by telephone before treatment (baseline), midtreatment, within 1 month post-treatment, and at 12, 18, and 24 months postbaseline by using questionnaires from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30), a breast systemic adverse effects scale (EORTC BR23), and the Hospital Anxiety and Depression Scale (HADS). Results Compared with patients who were treated with standard chemotherapy, patients who were treated with capecitabine had significantly better QoL, role function, and social function, fewer systemic adverse effects, less psychological distress, and less fatigue during and at the completion of treatment (P ≤ .005). Capecitabine treatment was associated with less nausea, vomiting, and constipation and with better appetite than standard treatment (P ≤ .004), but worse hand-foot syndrome and diarrhea (P < .005). These differences all resolved by 12 months. Conclusion Standard chemotherapy was superior to capecitabine in improving relapse-free and overall survival for older women with early-stage breast cancer. Although capecitabine was associated with better QoL during treatment, QoL was similar for both groups at 1 year. The brief period of poorer QoL with standard treatment is a modest price to pay for a chance at improved survival.

Download Full-text

Influence of Activation State of ErbB-2 (HER-2) on Response to Adjuvant Cyclophosphamide, Doxorubicin, and Fluorouracil for Stage II, Node-Positive Breast Cancer: Study 8541 From the Cancer and Leukemia Group B

Journal of Clinical Oncology ◽

10.1200/jco.2007.13.6580 ◽

2008 ◽

Vol 26 (14) ◽

pp. 2364-2372 ◽

Cited By ~ 4

Author(s):

Michael P. DiGiovanna ◽

David F. Stern ◽

Susan Edgerton ◽

Gloria Broadwater ◽

Lynn G. Dressler ◽

...

Keyword(s):

Breast Cancer ◽

Growth Factor Receptor ◽

Chemotherapeutic Agents ◽

High Dose ◽

Breast Cancer Study ◽

Dosing Regimens ◽

Her 2 ◽

Group B ◽

The Impact ◽

Leukemia Group

PurposeErbB-2 (human epidermal growth factor receptor 2) overexpression may be predictive of relative resistance and/or sensitivity to specific chemotherapeutic agents. Results from a previous study from the Cancer and Leukemia Group B (CALGB 8541) demonstrated an interaction between ErbB-2 and increasing dose of adjuvant cyclophosphamide, doxorubicin, and fluorouracil (CAF) chemotherapy. Other studies have suggested that evaluation of the phosphorylated/activated form of ErbB-2 might be more precise in defining the impact of ErbB-2 in breast cancer. We have evaluated tumor tissue sections from CALGB 8541 patients to determine whether the interaction of ErbB-2 with CAF dose is dependent on ErbB-2 activation state, and whether phosphorylated ErbB-2 is an adverse prognostic factor in patients treated with CAF.Patients and MethodsPatients were randomly assigned to one of three dosing regimens of CAF. Paraffin samples from 992 of 1,572 patients who participated in CALGB 8541 were available. Of the 570 tumors with any staining for ErbB-2, 488 had tissue available for assay for phosphorylated ErbB-2, which was performed by immunohistochemistry.ResultsOf 910 total assessable cases, 112 of 488 ErbB-2-positive cases (23%) stained positively for phosphorylated ErbB-2. The previously described interaction of dosing regimen of CAF with ErbB-2 was not dependent on phosphorylation status of ErbB-2.ConclusionMonitoring phosphorylation of ErbB-2 with an antiphospho-ErbB-2 antibody did not add further precision to identifying those patients most likely to benefit from increased dose of anthracycline-based adjuvant chemotherapy. Favorable outcomes are observed in ErbB-2-overexpressing patients treated with high-dose CAF regardless of ErbB-2 phosphorylation state.

Download Full-text

Patient Data Monitoring: Watchdog Technology that Detects Impending Adverse Events Lean Body Weight or Actual Body Weight?

Hospital Pharmacy ◽

10.1177/001857870303800906 ◽

2003 ◽

Vol 38 (9) ◽

pp. 818-821 ◽

Cited By ~ 1

Author(s):

Michael R. Cohen

Keyword(s):

Body Weight ◽

Adverse Events ◽

Actual Body ◽

Patient Data ◽

Data Monitoring ◽

Lean Body Weight ◽

Actual Body Weight

Download Full-text

Association between overall survival and adverse events with lenvatinib treatment in patients with hepatocellular carcinoma (REFLECT).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.4_suppl.317 ◽

2019 ◽

Vol 37 (4_suppl) ◽

pp. 317-317 ◽

Cited By ~ 7

Author(s):

Max W. Sung ◽

Richard S. Finn ◽

Shukui Qin ◽

Kwang-Hyub Han ◽

Kenji Ikeda ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Body Weight ◽

Adverse Events ◽

Actual Body ◽

Actual Body Weight ◽

Kaplan Meier ◽

Post Hoc ◽

To Receive ◽

Clinical Trial Information

317 Background: In the phase 3 REFLECT study, lenvatinib (LEN) demonstrated a treatment effect on overall survival (OS) by statistical confirmation of non-inferiority to sorafenib (SOR) in patients (pts) with unresectable hepatocellular carcinoma (uHCC), who had not received prior treatment for advanced disease (Kudo M et al, Lancet 2018). Lenvatinib is approved in several major markets for the first line systemic treatment of uHCC. The most common adverse events (AEs) in pts treated with LEN were hypertension and diarrhea. In addition, LEN showed a different AE profile from that of SOR. Pts who received LEN experienced more instances of hypertension, proteinuria, dysphonia, and hypothyroidism than patients who received SOR. Recently, hypertension in LEN-treated pts with differentiated thyroid cancer was shown to be correlated with improved efficacy. Here we report the post hoc analysis exploring whether AEs associated with LEN were correlated with longer OS in REFLECT. Methods: 478 Pts were randomized to receive LEN (12 mg/d for actual body weight ≥ 60 kg or 8 mg/d for actual body weight < 60 kg). Subgroup analyses were conducted based on whether pts treated with LEN experienced any-grade AEs of interest (AEIs). OS was estimated by the Kaplan-Meier method. Results: The AEIs in pts treated with LEN were hypertension (42%), diarrhea (38%), proteinuria (24%), dysphonia (24%), and hypothyroidism (16%). OS was longer in pts who had several AEs of interest than in those who did not (table). Conclusions: In pts treated with LEN, the occurrence of hypertension, diarrhea, proteinuria, or hypothyroidism was generally associated with longer OS in pts with uHCC in this post hoc exploratory analysis. The potential confounding factors at baseline should be further investigated. Clinical trial information: NCT01761266. [Table: see text]

Download Full-text