PURPOSE: To determine the absolute and relative value of microvessel density (MVD), p53 and c-erbB-2 protein expression, peritumoral lymphatic vessel invasion (PLVI), and conventional prognosticators in predicting relapse-free (RFS) and overall survival (OS) rates in patients with node-negative breast carcinoma (NNBC). PATIENTS AND METHODS: We monitored 254 consecutive patients with NNBC for a median of 62 months. Intratumoral MVD was measured after microvessels were immunostained using anti-CD31 antibody. p53 and c-erbB-2 protein and hormone receptors were also determined immunocytochemically. Results were analyzed by both univariate and multivariate statistical analysis. RESULTS: Univariate analysis showed that MVD was significantly predictive of both RFS (odds ratio [OR], 8.30; P = .0001) and OS (OR, 4.50; P = .012) when tested as a continuous or dichotomous variable. Likewise, tumor size (OR, 3.16; P = .0012), PLVI (OR, 4.36; P = .0009), estrogen receptor (ER) status (OR, 2.35; P = .016), progesterone receptor (PR) status (OR, 2.00; P = .017), and expression of p53 protein (OR, 2.82; P = .004) were significantly associated with RFS. Tumor size (OR, 3.80; P = .0038) and expression of p53 protein (OR, 2.58; P = .024) were significantly associated with OS by univariate analysis. Multivariate analysis showed that MVD (P = .0004), p53 protein expression (P = .0063), tumor size (P = .0144), and PLVI (P = .0033) were all significant and independent prognostic factors for RFS. However, only tumor size (P = .004) and MVD (P = .047) were independent predictors for OS. c-erbB2 expression was not associated with outcome by either univariate or multivariate analysis. CONCLUSION: MVD, p53 expression, PLVI, and tumor size are independent prognostic indicators of recurrence, which are useful in selection of high-risk NNBC patients who may be eligible to receive adjuvant therapies.

Purpose: In patients with metastatic castration-resistant prostate cancer (mCRPC), overall survival (OS) is significantly improved with cabazitaxel versus mitoxantrone after prior docetaxel treatment. FIRSTANA ( ClinicalTrials.gov identifier: NCT01308567) assessed whether cabazitaxel 20 mg/m² (C20) or 25 mg/m² (C25) is superior to docetaxel 75 mg/m² (D75) in terms of OS in patients with chemotherapy-naïve mCRPC. Patients and Methods: Patients with mCRPC and Eastern Cooperative Oncology Group performance status of 0 to 2 were randomly assigned 1:1:1 to receive C20, C25, or D75 intravenously every 3 weeks plus daily prednisone. The primary end point was OS. Secondary end points included safety; progression-free survival (PFS); tumor, prostate-specific antigen, and pain response; pharmacokinetics; and health-related quality of life. Results: Between May 2011 and April 2013, 1,168 patients were randomly assigned. Baseline characteristics were similar across cohorts. Median OS was 24.5 months with C20, 25.2 months with C25, and 24.3 months with D75. Hazard ratio for C20 versus D75 was 1.01 (95% CI, 0.85 to 1.20; P = .997), and hazard ratio for C25 versus D75 was 0.97 (95% CI, 0.82 to 1.16; P = .757). Median PFS was 4.4 months with C20, 5.1 months with C25, and 5.3 months with D75, with no significant differences between treatment arms. Radiographic tumor responses were numerically higher for C25 (41.6%) versus D75 (30.9%; nominal P = .037, without multiplicity test adjustment). Rates of grade 3 or 4 treatment-emergent adverse events were 41.2%, 60.1%, and 46.0% for C20, C25, and D75, respectively. Febrile neutropenia, diarrhea, and hematuria were more frequent with C25; peripheral neuropathy, peripheral edema, alopecia, and nail disorders were more frequent with D75. Conclusion: C20 and C25 did not demonstrate superiority for OS versus D75 in patients with chemotherapy-naïve mCRPC. Tumor response was numerically higher with C25 versus D75; pain PFS was numerically improved with D75 versus C25. Cabazitaxel and docetaxel demonstrated different toxicity profiles, with overall less toxicity with C20.

BACKGROUND: Syndecan‐1 is a transmembrane heparan sulphate proteoglycan that is involved in cell–cell adhesion, organization of cell–matrix adhesion, and regulation of growth factor signaling.METHODS: Specimens from 254 consecutive breast carcinoma (BC) cases (110 N0, 144 N1/2) with long‐term follow‐up (median, 95 months) were immunostained for syndecan‐1, estrogen receptor (ER), progesterone receptor (PgR), and p53; in 154 cases, c‐erbB‐2 status was known. Syndecan‐1 mRNA and protein expression also were evaluated in 20 breast tissue samples (10 normal and tumor pairs).RESULTS: Syndecan‐1 was expressed at high levels in 106 (42%) BCs; syndecan‐1 up‐regulation was confirmed by reverse transcriptase–polymerase chain reaction (RT‐PCR) studies. High syndecan‐1 expression was associated with high histologic grade, large tumor size, high mitotic count, c‐erbB‐2 overexpression, and ER and PgR negative status. At univariate survival analysis syndecan overexpression was related to poor prognosis (P < 0.01 for both overall survival (OS) and disease‐free survival). Bivariate survival analysis showed an additive adverse effect for syndecan‐1 and c‐erbB‐2 overexpression. At multivariate analysis, syndecan‐1 overexpression was independently associated with poor OS (hazard ratio [HR], 1.71; 95% confidence interval [CI], 1.08–2.69). High syndecan‐1 expression also was of independent prognostic value for OS in the group of 102 ER‐negative patients (HR, 2.42; 95% CI, 1.21–4.82). Stratifying patients on the basis of the type of adjuvant therapy given, high syndecan‐1 expression was associated with a higher risk of death only in patients treated with the cyclophosphamide‐methotrexate‐fluorouracil regimen (HR, 1.9; P = 0.09); at multivariate analysis for OS, this association proved to be of independent statistical significance (P = 0.03; HR, 2.15).CONCLUSIONS: Syndecan‐1 is expressed at high levels in a significant percentage of breast carcinomas and is related to an aggressive phenotype and poor clinical behavior. Cancer 2003;98:474–83. © 2003 American Cancer Society.DOI 10.1002/cncr.11515

Docetaxel (75 mg m⁻² 3-weekly) is standard second-line treatment in advanced non-small-cell lung cancer (NSCLC) with significant toxicity. To verify whether a weekly schedule (33.3 mg m⁻² for 6 weeks) improved quality of life (QoL), a phase III study was performed with 220 advanced NSCLC patients, 75 years, ECOG PS 2. QoL was assessed by EORTC questionnaires and the Daily Diary Card (DDC). No difference was found in global QoL scores at 3 weeks. Pain, cough and hair loss significantly favoured the weekly schedule, while diarrhoea was worse. DDC analysis showed that loss of appetite and overall condition were significantly worse in the 3-week arm in the first week, while nausea and loss of appetite were more severe in the weekly arm in the third week. Response rate and survival were similar, hazard ratio of death in the weekly arm being 1.04 (95% CI 0.77–1.39). A 3-weekly docetaxel was more toxic for leukopenia, neutropenia, febrile neutropenia and hair loss; any grade 3–4 haematologic toxicity was significantly more frequent in the standard arm (25 vs 6%). The weekly schedule could be preferred for patients candidate to receive docetaxel as second-line treatment for advanced NSCLC, because of some QoL advantages, lower toxicity and no evidence of strikingly different effect on survival.