ABSTRACT
BACKGROUND: The addition of trastuzumab (T) and lapatinib (L) to neoadjuvant chemotherapy increases the pathological complete response (pCR) rate in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. We investigated the efficacy of T or L with neoadjuvant chemotherapy and specific efficacy biomarkers. METHODS: Patients with stages I-III (including inflammatory) HER2-positive breast cancer were randomised to receive epirubicin (E) plus cyclophosphamide (C) × 4 cycles followed by docetaxel (D) plus either T (EC-DT) or L (EC-DL). End points included pCR (primary), clinical response, toxicity, and pCR-predictive biomarkers. RESULTS: We randomised 102 patients to EC-DT (50) and EC-DL (52). Median age was 48, 56% were premenopausal and 58% had oestrogen receptor (ER)-positive tumours. Pathological complete response in breast was 52.1% (95% CI:38.0-66.2%) for EC-DT and 25.5% (95% CI:13.5-37.5%) for EC-DL (P=0.0065). Pathological complete response in breast and axilla was 47.9% for EC-DT and 23.5% for EC-DL (P=0.011). Grade 3-4 toxicity did not differ across treatments, except for diarrhoea (2% in EC-DT vs 13.5% in EC-DL, P=0.030). Multivariate analyses showed that treatment (P=0.036) and ER (P=0.014) were the only predictors of pCR in both groups. CONCLUSION: EC-DT exhibited higher efficacy and lower toxicity than EC-DL. Of the different biomarkers studied, only the absence of ER expression was associated with increased pCR.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Receptor, ErbB-2/biosynthesis , Adult , Aged , Antibodies, Monoclonal, Humanized/administration & dosage , Biomarkers, Tumor/biosynthesis , Biomarkers, Tumor/genetics , Breast Neoplasms/enzymology , Breast Neoplasms/genetics , Cyclophosphamide/administration & dosage , Docetaxel , Epirubicin/administration & dosage , Female , Humans , Lapatinib , Middle Aged , Neoadjuvant Therapy/methods , Quinazolines/administration & dosage , Receptor, ErbB-2/genetics , Taxoids/administration & dosage , TrastuzumabABSTRACT
BACKGROUND: we previously reported a phase I trial of liposome-encapsulated doxorubicin citrate (LD), docetaxel and trastuzumab as neoadjuvant in stages II and IIIA human epidermal growth factor receptor 2-overexpressing breast cancer patients. This study evaluates the efficacy of this regimen in a phase II trial. PATIENTS AND METHODS: patients were treated with LD 50 mg/m(2) and docetaxel 60 mg/m(2) every 21days associated with standard trastuzumab dose and pegfilgrastim support. RESULTS: fifty-nine patients were enrolled; median age: 48 years (range 24-71 years); premenopausal patients: 36 (61%); 19 patients (32%) presented stage IIIA disease and 40 patients (67%) stage II; histological grades 2-3 tumors: 50 patients (84%) and estrogen receptor-progesterone receptor negative: 28 patients (47%). In all, 27% achieved a pathological complete response in breast and axilla (grade 5-Miller and Payne classification); 15% of patients achieved grade 4. Clinical and radiological response rates were 86% and 81%, respectively. Forty-two patients (71%) underwent breast-conserving surgery. The main grades 3-4 toxic effects were non-febrile neutropenia (29%) and fatigue (8%). Grade 2 left ventricular ejection fraction decline was observed in nine patients. No congestive heart failure was observed. CONCLUSIONS: LD plus docetaxel combination associated with trastuzumab as neoadjuvant is active in breast cancer and entails a favorable cardiotoxicity profile. This regimen is a new treatment option in these patients.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Receptor, ErbB-2/biosynthesis , Adult , Aged , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Breast Neoplasms/enzymology , Breast Neoplasms/pathology , Docetaxel , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Female , Filgrastim , Granulocyte Colony-Stimulating Factor/administration & dosage , Humans , Middle Aged , Neoadjuvant Therapy , Neoplasm Staging , Polyethylene Glycols , Receptor, ErbB-2/antagonists & inhibitors , Recombinant Proteins , Taxoids/administration & dosage , Taxoids/adverse effects , Trastuzumab , Young AdultABSTRACT
In Spain, neither the HIV nor the STI national surveillance systems collect information on HIV/STI co-infection. However, there are two networks based on HIV/STI clinics which gather this data. We describe HIV prevalence in men who have sex with men (MSM) diagnosed with infectious syphilis and/or gonorrhoea in 15 STI clinics; and concurrent diagnoses of STI in MSM newly diagnosed with HIV in 19 HIV/STI clinics. In total, 572 MSM were diagnosed with infectious syphilis and 580 with gonorrhoea during 2005-2007. HIV prevalence among syphilis and gonorrhoea cases was 29.8% and 15.2% respectively. In the multivariate analysis, HIV/syphilis co-infection was associated with being Latin American; having a history of STI; reporting exclusively anal intercourse; and having sex with casual or several types of partners. HIV and gonorrhoea co-infection was associated with age older than 45 years; having no education or only primary education completed; and having a history of STI. In total, 1,462 HIV infections were newly diagnosed among MSM during 2003-2007. Of these, 31.0% were diagnosed with other STI at the same time. Factors associated with STI co-infection among new HIV cases in MSM were being Latin American; and having sex with casual partners or with both steady and casual partners. In Spain, a considerable proportion of MSM are co-infected with HIV and STI.
