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Background In order to determine the feasibility of substituting pegylated liposomal doxorubicin (PLD) for doxorubicin in combination with cyclophosphamide and trastuzumab as adjuvant therapy, we conducted a phase II study of the combination as first-line therapy in human epidermal growth factor receptor 2 (HER2) overexpressing metastatic breast cancer (MBC). Methods PLD 50 mg/m2 and cyclophosphamide 600 mg/m2 were administered every 4 weeks for six cycles; trastuzumab (4 mg/kg loading dose, then 2 mg/kg) was administered weekly for 24 weeks. The primary end point was objective response rate (ORR), and the secondary end points included time to progression (TTP), overall survival (OS), and safety. Results Among the 48 evaluable patients, ORR was 68.8% [95% confidence interval (CI) 55.69% to 81.91%], with 6 patients (12.5%) achieving a complete response and 27 (56.2%) a partial response. The median TTP was 12 months (95% CI 9–15.1 months), and the median OS was 34.2 months (95% CI 27.2–41.2 months). Febrile neutropenia was seen in three patients, grade 3 hand–foot syndrome in 29.2% of patients, and grade 3–4 mucositis in 22.9% of patients. Symptomatic congestive heart failure was not observed, and 16.7% of patients experienced grade 2 asymptomatic left ventricular systolic dysfunction. Conclusion The combination of PLD–cyclophosphamide–concurrent trastuzumab is a feasible, safe, and effective first-line regimen for HER2-overexpressing MBC.

Summary Background We aimed to compare the additional benefit of gemcitabine when combined with vinorelbine above that of standard vinorelbine treatment in patients with metastatic breast cancer. Methods In this phase III, multicentre, open-label, randomised study, 252 women with locally recurrent and metastatic breast cancer who had been pretreated with anthracyclines and taxanes were randomly assigned single-agent vinorelbine (30 mg/m 2 , days 1 and 8) or gemcitabine plus vinorelbine (1200/30 mg/m 2 , days 1 and 8). Both study treatments were administered intravenously every 21 days until disease progression, unacceptable toxic effects, or stoppage at the request of investigator or patient. The primary endpoint was median progression-free survival. Secondary objectives included assessments of response rate, disease duration, overall survival, and characterisation of the toxicity profiles of both regimens. This study is registered with ClinicalTrials.gov, number NCT00128310. Findings Between 2001 and 2005, 252 women were recruited and randomised for treatment. One of these patients was ineligible. Prognostic factors were well balanced between treatment groups (median number of metastatic sites in combination group 2 (range 0–5) and in vinorelbine group 2 (range 1–6); visceral disease in 76% and 75% of patients, respectively). Median progression-free survival was 6·0 months (95% CI 4·8–7·1) for patients given gemcitabine plus vinorelbine and 4·0 months (2·9–5·1) for those assigned vinorelbine; there was 1·9 months of difference (hazard ratio 0·66 [0·50–0·88]; p=0·0028). Overall survival was 15·9 months (12·6–19·1) for the gemcitabine plus vinorelbine group and 16·4 months (11·6–21·0) for the vinorelbine group; there was 0·5 months of difference (hazard ratio 1·04 [0·78–1·39]; p=0·8046). Objective response rates were 36% for patients assigned gemcitabine plus vinorelbine (n=45) and 26% for those assigned vinorelbine (n=33) (p=0·093). Grade 3 or 4 neutropenia was reported in 75 (61% [52–70]) of the participants assigned gemcitabine plus vinorelbine, compared with 55 (44% [35–53]) of those assigned vinorelbine alone (p=0·0074). Febrile neutropenia occurred in 13 (11%) of those assigned gemcitabine plus vinorelbine, and in seven (6%) of those assigned vinorelbine alone (p=0·15). Incidences of grade 3 or 4 non-haematological toxic effects were similar between the two treatment groups. Interpretation Patients with metastatic breast cancer assigned gemcitabine and vinorelbine had better progression-free survival compared with those assigned vinorelbine alone. However, this finding did not translate into a difference in overall survival. Although toxicity was manageable, patients in the combined group had more haematological toxic effects. These factors should be taken into account when deciding which chemotherapy patients should receive.

Background: The aim of the study was to analyse the toxicity and health related quality of life (HRQoL) of breast cancer patients treated with FAC (5-fluorouracil, doxorubicin, cyclophosphamide) and TAC (docetaxel, doxorubicin, cyclophosphamide) with and without primary prophylactic G-CSF (PPG). Patients and methods: This was a phase III study to compare FAC and TAC as adjuvant treatment of high-risk node-negative breast cancer patients. After the entry of the first 237 patients, the protocol was amended to include PPG in the TAC arm due to the high incidence of febrile neutropenia. A total of 1047 evaluable patients from 49 centres in Spain, two in Poland and four in Germany were included in the trial. Side-effects and the scores of the EORTC QLQ-C30 and QLQ BR-23 questionnaires were compared in the three groups (FAC, TAC pre-amendment and TAC post-amendment). Results: The addition of PPG to TAC significantly reduced the incidence of neutropenic fever, grade 2–4 anaemia, asthenia, anorexia, nail disorders, stomatitis, myalgia and dysgeusia. Patient QoL decreased during chemotherapy, more with TAC than FAC, but returned to baseline values afterwards. The addition of PPG to TAC significantly reduced the percentage of patients with clinically relevant Global Health Status deterioration (10 or more points over baseline value) at the end of chemotherapy (64% versus 46%, P < 0.03). Conclusions: The addition of PPG significantly reduces the incidence of neutropenic fever associated with TAC chemotherapy as well as that of some TAC-induced haematological and extrahaematological side-effects. The HRQoL of patients treated with TAC is worse than that of those treated with FAC but improves with the addition of PPG, particularly in the final part of chemotherapy treatment.

Background Sorafenib (SOR) is a potent inhibitor of c-Raf, b-Raf VEGFR-1/2/3 and PDGFR-β. In NSCLC, proliferative signaling through the Ras/Raf/MEK/ERK pathway is often activated from K-ras mutations. Their efficacy as monotherapy for treating advanced NSCLC has been demonstrated in several trials. In them, SOR improved the rate of disease stabilization in patients who had previously been treated with chemotherapy. Our objective is to confirm the clinical and safety results in daily clinical activity. Methods Between October 2008 and December 2011, 16 Caucasian patients with metastatic NSCLC and measurable disease were treated after having received two or more prior lines of therapy for metastatic disease.SOR was administered at a starting dose of 400 mg bid continuously in 28-day cycles.The primary end-point was Progression Free Survival (PFS). The secondary end-points were Overall Survival (OS) and Response Rate (RR). Results Median age was 59 years (40-86). 100% patients were PS (ECOG) 0/1 (5/11, 31/69%). Most were males (n = 10, 62%). The predominant histologic type was adenocarcinoma (n = 10, 62%). Thirteen (81%) patients were in stage IV at diagnosis. The predominant metastatic sites were lung (n = 9, 56%), lymph nodes, (n = 6, 38%), pleura (n =3, 19%) and bone (n = 3, 19%) Patients received a median of 3 (range: 2 to 4) treatment lines prior to the SOR regimen; Eleven (68.8%) patients received at least 3 treatment lines before SOR. The median duration of the SOR regimen was 114 days (9-247).Median PFS and median OS were 2.8 and 3.3 months, respectively. After administration of SOR, 2 patients (13%) had a partial response and 5 (33%) had stable disease. The toxicity profile was mild. Adverse events CTC G3/4 were dyspnea (n = 4, 25%), skin toxicity (n = 1, 6%) and vomiting (n = 1, 6%). In 1 case, treatment was interrupted by non-hematological toxicity. Conclusions Patients with advanced NSCLC receiving SOR after two or more lines of therapy got a 2.8 and 3.3 months median PFS and OS, respectively, with a 46% Disease Control Rate and with an acceptable safety profile. While still waiting for the results of ongoing trials, SOR is active and safe in this widely treated patient population. Disclosure All authors have declared no conflicts of interest.