Adjuvant anastrozole versus exemestane versus letrozole, upfront or after 2 years of tamoxifen, in endocrine-sensitive breast cancer (FATA-GIM3): a randomised, phase 3 trial
Background: Uncertainty exists about the optimal schedule of adjuvant treatment of breast cancer with aromatase inhibitors and, to our knowledge, no trial has directly compared the three aromatase inhibitors anastrozole, exemestane, and letrozole. We investigated the schedule and type of aromatase inhibitors to be used as adjuvant treatment for hormone receptor-positive early breast cancer. Methods: FATA-GIM3 is a multicentre, open-label, randomised, phase 3 trial of six different treatments in postmenopausal women with hormone receptor-positive early breast cancer. Eligible patients had histologically confirmed invasive hormone receptor-positive breast cancer that had been completely remov…
Phase 3 randomized study of adjuvant anastrozole (A), exemestane (E), or letrozole (L) with or without tamoxifen (T) in postmenopausal women with hormone-responsive (HR) breast cancer: The FATA-GIM3 trial.
515 Background: Uncertainty still exists regarding the optimal schedule of adjuvant treatment of breast cancer with aromatase inhibitors (AI) and no trial has ever compared all the three AI. Methods: FATA-GIM3 is a multicenter, open label, 2x3 factorial phase 3 randomized study of adjuvant A, E and L upfront (UP - for 5 years) or sequentially (SEQ - for 3 years after 2 years of T) in postmenopausal HR breast cancer pts. Two comparisons were planned: UP vs SEQ and A vs E vs L. DFS (including local or distant relapse, second breast or non-breast cancer, DCIS and death, whichever came first) was the primary end-point; 2% at 5 yrs (corresponding to a HR of 0.79) was defined as the minimum diff…
Mitomycin C plus vindesine plus etoposide (MEV) versus mitomycin C plus vindesine plus cisplatin (MVP) in stage IV non-small-cell lung cancer: A phase III multicentre randomised trial
Purpose : To compare mitomycin C plus vindesine plus etoposide (MEV) vs. mitomycin C plus vindesine plus cisplatin (MVP) in the treatment of stage IV non-small-cell lung cancer. Patients and methods : 204 patients were entered in a phase III multicentre randomised trial from June 1990 to December 1994 and stratified according to the ECOG performance status (0-1 vs. 2). MVP was given in the following dosages : mitomycin C 8 mg/m 2 + vindesine 3 mg/m 2 + cisplatin 100 mg/m 2 i.v. day 1 and vindesine 3 mg/m 2 i.v. day 8 with cycles repeated every 4 weeks. MEV was given in the following dosages : mitomycin C 8 mg/m 2 + vindesine 3 mg/m 2 i.v. day I and etoposide 100 mg/m 2 i.v. days 1 to 3 with…
Carboplatin and pegylated liposomal doxorubicin for advanced ovarian cancer. Preliminary activity results of the MITO-2 phase III trial
<i>Background:</i> Based on the efficacy of pegylated liposomal doxorubicin (PLD) in relapsed ovarian cancer, we are conducting a phase III study comparing carboplatin plus either paclitaxel or PLD as first-line therapy in advanced ovarian cancer. Because of limited phase I and II data on PLD plus carboplatin in this setting, we conducted an interim activity analysis. <i>Patients and Methods:</i> Patients with stage 1c-IV epithelial ovarian cancer were randomized to carboplatin AUC 5 plus either paclitaxel 175 mg/m<sup>2</sup> or PLD 30 mg/m<sup>2</sup> every 3 weeks for 6 cycles. The interim activity analysis was planned according to a single…
Management and treatment of triple-negative breast cancer patients from the NEMESI study: An Italian experience
Abstract Aims Triple-negative breast cancers (TNBCs) lack expression of oestrogen, progesterone, and Human Epidermal Growth Factor 2 receptors. The NEMESI study described current Italian treatment practices in patients with operable, early-stage breast cancer (EBC). Patients and methods Retrospective, observational study involving 63 Italian oncology centres. Eligible patients were aged ⩾18 years with EBC (stage I–II) who had undergone surgery, received ⩾1 cycle of adjuvant chemotherapy and/or adjuvant hormonal therapy and attended an oncology centre between 1 January 2008 and 30 June 2008. This subanalysis focused on patients with TNBC. Variables evaluated included: demographic data/clinic…
RANDOMIZED PHASE II STUDY OF FIRST-LINE EVEROLIMUS (EVE) + BEVACIZUMAB (BEV) VERSUS INTERFERON ALFA-2A (IFN) + BEV IN PATIENTS (PTS) WITH METASTATIC RENAL CELL CARCINOMA (MRCC): RECORD-2
ABSTRACT Background Study results demonstrated that IFN augments BEV activity and improves median PFS in pts with mRCC. Thus, combination BEV + IFN is a standard first-line treatment option for mRCC. Combining BEV with the mTOR inhibitor EVE may be an efficacious and well-tolerated treatment option. The open-label, phase II RECORD-2 trial compared first-line EVE + BEV and IFN + BEV in mRCC. Patients and methods: Therapy-naive pts with clear cell mRCC and prior nephrectomy were randomized 1:1 to BEV 10 mg/kg IV every 2 weeks with either EVE 10 mg oral daily or IFN (9 MIU SC 3 times/week, if tolerated). Tumour assessments were every 12 weeks. Primary objective was treatment effect on progress…
PTEN status is a crucial determinant of the functional outcome of combined MEK and mTOR inhibition in cancer
AbstractCombined MAPK/PI3K pathway inhibition represents an attractive, albeit toxic, therapeutic strategy in oncology. Since PTEN lies at the intersection of these two pathways, we investigated whether PTEN status determines the functional response to combined pathway inhibition. PTEN (gene, mRNA, and protein) status was extensively characterized in a panel of cancer cell lines and combined MEK/mTOR inhibition displayed highly synergistic pharmacologic interactions almost exclusively in PTEN-loss models. Genetic manipulation of PTEN status confirmed a mechanistic role for PTEN in determining the functional outcome of combined pathway blockade. Proteomic analysis showed greater phosphoprote…
Treatment of recurrent and/or metastatic squamous cell head and neck carcinoma with a combination of vinorelbine, cisplatin, and 5-fluorouracil: a multicenter phase II trial.
Summary Purpose Vinorelbine has been demonstrated to be active against squamous cell carcinomas of the headneck (SCHNC) and lung. This multicenter phase II trial was carried out to evaluate the activity and tolerability of the combination of vinorelbine, cisplatin, and 5-fluorouracil given on an outpatient schedule in a series of 80 patients with recurrent SCHNC. Patients and methods Eighty patients with recurrent and/ or metastatic SCHNC were treated with a combination of CDDP 80 mg/m2 on day 1, 5-FU 600 mg/m2 as a 4-hour infusion on days 2-5, and vinorelbine 25 mg/m2 on days 2 + 8. This cycle was repeated every 28 days. Most patients had oral cavity, larynx, or oropharynx carcinoma (88%).…
Synergistic Growth Inhibitory Activity of Combined Mek/Mtor Pathway Blockade in Pten-Null Cancers
ABSTRACT Aim: We have recently shown that induction of PTEN expression plays an integral role in MEK inhibitors' antitumor activity. Here we hypothesize that PTEN status critically influences the functional outcome of combined MEK and PI3K/mTOR inhibition. Methods: Single and combined MEK (trametinib, T) and mTOR (everolimus, E) blockade were assessed in a panel of cancer cell lines and in patient-derived lung and colon cancer stem cells (L- or C-CSC). Pharmacologic interactions were analyzed by conservative isobologram analysis. PTEN role was assessed by shRNA-mediated silencing or overexpression by stable transfection. Treatment-induced changes in the phosphoproteome were analyzed by anti…