Background The efficacy and feasibility of chemotherapy in elderly metastatic breast cancer (MBC) patients (pts) have been studied in various phase II studies. However, results of prospective randomized studies in elderly MBC pts are scarce. Methods In this phase III multicenter study, MBC pts ≥ 65 years eligible for first-line chemotherapy were randomized between pegylated liposomal doxorubicin (PEGdoxo) (45mg/m2, IV, q 4 wks) or capecitabine (Cape) (1000 mg/m2 PO bid, days 1–14, q 3 wks). Other eligibility criteria were ECOG performance status (PS) ≤ 2 (3 allowed if due to pain or pre existing comorbidity), adequate bone marrow and organ functions. Stratification factors were PS (0–1 vs 2–3), HER2 status, visceral/non-visceral disease, adjuvant hormonal therapy (HTx), and HTx for MBC. Baseline geriatric assessment (GA) included functional status, instrumental activities of daily living, cognition, mood, comorbidity, polypharmacy and nutritional status. Chemotherapy was continued for 24 wks in the absence of progressive disease (PD) or unacceptable toxicity. Primary endpoint was progression-free survival (PFS), secondary endpoints were response rate, overall survival (OS), toxicity (CTC criteria) and compliance. Results Between April 2007 and August 2011, 78 pts were randomized to PEGdoxo (n = 40) or Cape (n = 38). The study was prematurely closed due to slow accrual and supply problems with PEGdoxo. Mean age was 74 years (range 65–86; 75+ 54%; 80+ 13%). Pt characteristics were balanced between the two arms: PS 0–1 77%, ER+ 68%, HER2+ 5%, visceral/non-visceral disease 76%/24%, adjuvant HTx 46%, HTx for MBC 56%, ≥ 3 metastatic sites 50%. Only 22 out of 75 pts with a baseline GA had no geriatric condition (29%), while 32 pts (43%) and 21 pts (28%) had one or ≥ 2 geriatric conditions, respectively. Chemotherapy was given for 6 months in 38%, with a mean dose intensity of 84% in both arms. Reasons for early treatment discontinuation were: PD (31%), toxicity (28%), pt withdrawal (3%). After a median follow up of 32 months, 74 pts had PD and 56 pts had died. The median PFS was 5.7 and 7.7 months with PEGdoxo and Cape (HR 0.68, 95% CI: 0.42–1.11, p = 0.12) and the median OS was 13.8 and 16.8 months, respectively (HR 0.84, 95% CI: 0.49–1.42, p = 0.51). Response was evaluable in 64 pts, with a partial response (PR) in 7 (21%) and 6 pts (19%), and stable disease in 21 (64%) and 17 pts (55%) for PEGdoxo and Cape, respectively. Toxicity was acceptable, mainly being grade 1–2, with for PEGdoxo/Cape grade 1 alopecia in 14/4 pts (grade 2 in 1 PEGdoxo pt), grade 3 fatigue in 5/5 pts, grade 3 HFS in 4/6 pts and grade 3 mucositis in 4/1 pts, respectively. Pts with ≥ 1 geriatric condition more frequently experienced grade 3–4 toxicity, after correcting for type of chemotherapy, age and PS (HR 2.24, 95% CI: 1.21–4.16). Pts aged 75+ had a twofold higher risk of dying, irrespective of treatment arm (HR 2.31, 95% CI: 1.31–4.07). Conclusions First-line chemotherapy with either PEGdoxo or Cape was feasible in elderly MBC pts, with adequate dose intensity and acceptable toxicity, even in non-fit pts or pts aged 75+. Baseline GA correlated with toxicity. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-12-05.

Background: Preclinical evidence shows that short-term fasting (STS) protects normal cells and makes cancer cells more vulnerable to chemotherapy. This pilot study examines the feasibility and the effects of STS on tolerance to chemotherapy in patients with breast cancer. Patients and methods: Eligible patients had histologically confirmed, HER2-negative, early stage breast cancer and adequate bone marrow, liver and renal function. Women receiving (neo) adjuvant TAC courses (docetaxel/adriamycin/cyclophosphamide; day 1, q 3 weeks with G-CSF support at day 2) were randomized to fast 24 hours before and 24 hours after start of chemotherapy or to eat according to the guideline for healthy nutrition. The primary endpoint of the study was to compare neutrophil count after therapy. Secondary endpoints were side effects of chemotherapy, other hematologic counts and chemotherapy-induced DNA damage in leukocytes. Results: A total of 13 patients were included of which 7 patients fasted for 48 hours around the chemotherapy infusion (arm A) and 6 patients had a normal diet according to healthy nutrition guidelines (arm B). The median age was 52 years versus 53 years, BMI was 25.5 kg/m2 versus 22.9 kg/m2 and stage III was 43% versus 17% of patients in arms A and B, respectively. Patients were generally motivated to fast and the fasting was well tolerated. Plasma glucose levels were significant lower in fasting patients compared to controls. However, other metabolic parameters showed no significant difference. Fasting did not result in significant differences in neutrophil count or side effects of chemotherapy. Hemoglobin levels and erythrocyte counts after therapy were significantly higher in patients who fasted. Leukocytes of the patients which were isolated at various time points during therapy will soon be analysed for chemotherapy-induced DNA damage and presented at San Antonio. Conclusion: This is the first study evaluating the feasibility of 48 hours STS and its impact on side effects of chemotherapy in a homogeneous group of cancer patients. STS was well tolerated and had a beneficial effect on hemoglobin level, but not on experienced side effects. DNA analysis will follow. Larger studies are required to produce more insight into the possible benefits of STS during chemotherapy. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-16-12.

Background: First-line treatment of HER2−negative LR/MBC with paclitaxel (T) and bevacizumab (A) has demonstrated improved progression-free survival (PFS) and overall response rate (ORR) when compared with T alone (E2100). We determined whether addition of capecitabine (X) to AT is safe and would be better effective than AT in women with HER2−negative LR/MBC. Methods: Eligibility criteria were age ≥18 & ≤75 years, measurable or non-measurable HER2−negative LR/MBC, ECOG PS 0–1 and no prior chemotherapy for LR/MBC. Patients were randomized in 1:1 ratio to receive AT (4-week cycle of T 90 mg/m2 on days 1, 8, 15 and A 10 mg/kg on days 1, 15 for 6 cycles, followed by A 15 mg/kg on day 1 given 3-weekly for subsequent cycles) or ATX (3-week cycle of T 90 mg/m2 on days 1, 8, A 15 mg/kg on day 1 and X 825 mg/m2 bid on days 1–14 for 8 cycles, followed by A 15 mg/kg on day 1 and X 825 mg/m2 bid on days 1–14 given 3-weekly for subsequent cycles). Treatment was discontinued at disease progression, unmanageable toxicity or withdrawal of consent. The primary endpoint was PFS. Secondary endpoints were overall survival, ORR, duration of response and toxicity. Efficacy was evaluated according to RECIST 1.0 and toxicity was assessed according to NCI CTCAE 3.0. Results: From June 2007 till December 2010, 312 patients were recruited at 36 sites. The median age was 56 years (range 32–76). Among all patients, 52% had ECOG 0, 85% were hormone-receptor positive, 86% had measurable disease and 8% had bone-only metastases. These factors were well balanced between both arms. A total of 48% and 33% of patients, respectively, received prior hormonal therapy or radiotherapy for LR/MBC. At the data cut-off of 1st June 2011, the median follow-up duration was 23 months. 311 patients received at least one cycle of treatment and were evaluable for safety. The median number of treatment cycles in AT was 9 and in ATX was 11 (both 33 weeks). An ORR of ≥40% was reached in patients with measurable disease in both groups. The incidence of serious adverse events (SAEs) was 47% and 40% for AT and ATX, respectively, while that of treatment-related SAEs was 12% and 19%, respectively. Treatment-related deaths were 2% for AT and 2% for ATX. The overall rate of AEs grade 3 or 4 was similar in both arms as shown in Table 1, except for hand-foot syndrome grade 3 and neutropenia grade 3 in ATX. In addition, 6 patients with pulmonary embolism were reported in ATX. Conclusions: ATX was well tolerable, although more patients experienced hand-foot syndrome grade 3 and thromboembolic events than patients treated with AT. The efficacy data will be presented at the meeting. Support: This study was supported by Roche. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD07-07.