Feasibility and safety of dose-dense docetaxel after conventional epirubicin and cyclophosphamide as adjuvant treatment for early breast cancer patients.

BACKGROUND: Although dose-dense chemotherapy may reduce breast cancer recurrence and death, phase II studies show that dose-dense docetaxel is poorly tolerated following administration of dose-dense anthracycline-based chemotherapy mainly because of cutaneous toxicity. MATERIAL AND METHODS: This pilot study was designed to explore feasibility and safety of dose-dense docetaxel after conventional anthracycline-based therapy. Treatment consisted of sequential administration of 4 cycles of 3-weekly epirubicin (90 mg/m(2)) plus cyclophosphamide (600 mg/m(2)), followed by 4 cycles of bi-weekly docetaxel with pelfilgrastim on day 2 of each docetaxel cycle. Two docetaxel dose levels were planned: 75 mg/m(2) (D75) and 100 mg/m(2) (D100). Patients could only be assigned to the higher docetaxel dose if no early treatment discontinuations due to toxicity were seen, and a median relative dose intensity of docetaxel >90% among the first 5 evaluable patients was achieved. RESULTS: Fifty three patients received 4 cycles of epirubicin/cyclophosphamide (EC). Six patients withdrew from study before commencing docetaxel: four for toxicity, and two who declined further study participation. Eight patients, 2 in the first dose level and 6 in the second dose level, stopped treatment for toxicity after the first cycle of docetaxel and before densification. Therefore these events were not considered early treatment discontinuations. No patients required dose interruption after the second docetaxel administration. Overall 5 patients in the first dose level and 34 patients in the second dose level received 4 cycles of accelerated (dose-dense) docetaxel. No grade 3 or grade 4 toxicities occurred at the first dose level. No grade 4 toxicities occurred at the second dose level, while grade 3 toxicities occurring in >2 patients were myalgia and bone pain (5 and 8 patients respectively, 13% and 20%) and skin-nail toxicity (7 patients, 21%). No dose-reductions or significant treatment delays were required, translating to median relative dose intensity of 100% for docetaxel 75 mg/m(2), and 99% for 100 mg/m(2). CONCLUSIONS: Administration of docetaxel 100 mg/m(2) bi-weekly after conventional EC is feasible in selected early breast cancer patients. Lack of prior exposure to dose-dense anthracycline, as well as the use of stringent criteria implemented in the treatment protocol, might explain the improved safety profile and high treatment compliance observed in this study.

Evaluation of the cardiovascular health study (CHS) instrument and the Vulnerable Elders Survey-13 (VES-13) in elderly cancer patients. Are we still missing the right screening tool?

BACKGROUND: A geriatric screening tool would be valuable to identify elderly cancer patients who might benefit from a comprehensive geriatric assessment (CGA). This study evaluated the accuracy of the cardiovascular health study (CHS) instrument in predicting abnormality in CGA. The vulnerable elders' survey-13 (VES-13) was also evaluated. PATIENTS AND METHODS: Patients aged ≥ 70 years with solid tumors underwent a CGA after being screened with the CHS and VES-13. Analyses were conducted for the overall population and according to the disease status (early or advanced) and type of early cancer (breast or gastrointestinal, GI). RESULTS: Of 259 patients, 75% were impaired according to the CHS and 47% according to the VES-13. CGA impairment was reported in 171 patients (66%). In the overall population, overall accuracy, sensitivity and specificity of CHS in identifying CGA impairments were 74%, 87% and 49%, respectively. The corresponding figures for the VES-13 were 68%, 62% and 81%. Sensitivity and specificity of CHS in predicting CGA impairments in subgroups were early 81% and 55%, advanced 98% and 29%; early breast 78% and 69%, early GI 87.5% and 19%. CONCLUSIONS: The CHS compared favourably with VES-13 for sensitivity. However, the great variability in specificity observed with the CHS within subgroups limits its applicability in the global population.

Identification of a serum-detectable metabolomic fingerprint potentially correlated with the presence of micrometastatic disease in early breast cancer patients at varying risks of disease relapse by traditional prognostic methods.

BACKGROUND: Prognostic tools in early breast cancer are inadequate. The evolving field of metabolomics may allow more accurate identification of patients with residual micrometastases. PATIENTS AND METHODS: Forty-four early breast cancer patients with pre- and postoperative serum samples had metabolomic assessment by nuclear magnetic resonance. Fifty-one metastatic patients served as control. Differential clustering was identified and used to calculate individual early patient 'metabolomic risk', calculated as inverse distance of each early patient from the metastatic cluster barycenter. Metabolomic risk was compared with Adjuvantionline 10-year mortality assessment. RESULTS: Innate serum metabolomic differences exist between early and metastatic patients. Preoperative patients were identified with 75% sensitivity, 69% specificity and 72% predictive accuracy. Comparison with Adjuvantionline revealed discordance. Of 21 patients assessed as high risk by Adjuvantionline, 10 (48%) and 6 (29%) were at high risk by metabolomics in pre- and postoperative settings, respectively. Of 23 low-risk patients by Adjuvantionline, 11 (48%) preoperative and 20 (87%) postoperative patients were at low risk by metabolomics. CONCLUSIONS: This study identifies metabolomic discrimination between early and metastatic breast cancer. Micrometastatic disease may account for metabolomic misclassification of some early patients as metastatic. Metabolomics identifies more patients as low relapse risk compared with Adjuvantionline. Further exploration of this metabolomic fingerprint is warranted.