Metastatic hormone-sensitive prostate cancer benefits from upfront treatment intensification. To date, we do not have a validated prognostic model to guide treatment choice. In our study, docetaxel-treated patients with high Gleason score, high disease burden, pain or unfavorable laboratory parameters at baseline had worse outcomes. These results may be useful in tailoring treatment in this setting. Background: Treatment of metastatic hormone-sensitive prostate cancer (mHSPC) dramatically changed. PEACE-1 and ARASENS trials established triplet therapy efficacy. Identifying prognostic factors supporting treatment choice is pivotal. Methods: TEAM is an observational, retrospective study to evaluate prognostic role of variables in mHSPC patients receiving upfront docetaxel in 11 Italian centers. Outcome measures were progression-free survival (PFS) and overall-survival (OS). Results: From September 2014 to December 2020, 147 patients were included. Median PFS and OS were 11.6 and 37.4 months. At univariate analysis, PFS-related variables were Gleason Score (GS) ( P = .001), opioid use ( P = .004), bone metastases number ( P < .001), baseline PSA ( P = .006), Hb ( P < .001), ALP ( P < .001) and LDH ( P = .002), time between ADT and docetaxel start ( P = .018), 3-month PSA ( P < .001) and ALP ( P < .001), and number of docetaxel cycles ( P < .001). OS-related variables were PSA at diagnosis ( P = .024), primary tumor treatment ( P = .022), baseline pain ( P = .015), opioid use ( P < .001), bone metastases number ( P < . 001), baseline Hb ( P < .001), ALP ( P < .001) and LDH ( P = .001), NLR ratio ( P = .039), 3 -month PSA ( P < .001) and ALP ( P < .001) and docetaxel cycles number ( P < .001). At multivariate analysis, independent prognostic variables were GS, opioid use, baseline LDH and time between ADT and docetaxel initiation for PFS, and baseline Hb and LDH for OS. Conclusion: Patients receiving upfront docetaxel with high GS, high disease burden, pain or opioid use, baseline unfavorable laboratory values had worse outcomes. Patients had greater docetaxel benefit when initiated early after ADT start. These parameters could be taken into account when selecting candidates for triplet therapy.

Charts of all breast cancer patients affected by bone metastases observed at the Oncology Unit of Alessandria Hospital in years 2005-2020 have been reviewed. Osteonecrosis of the Jaw (ONJ) frequency after antiresorptive treatment (bisphosphonates and/or denosumab) was investigated in breast cancer patients undergoing preventive (before start of treatment) and/or screening (during treatment) evaluations, including oral inspection and panoramic dental radiography. Patients received antiresorptive agents according to international guidelines, that partially recommended shorter and tailored duration of antiresorptive treatment (instead of indefinite prolonged administration, till to deterioration of Performance Status - as advised by older guidelines) only after 2008. We examined charts of 280 patients with bone metastases receiving bisphosphonates (mostly zoledronic acid or pamidronate) or denosumab or sequences of drugs, and evaluated for oral health, of which 196 treated after 2006, and undergoing pre-treatment evaluation. Out of 280 total patients, 24 cases of Osteonecrosis of the Jaw (ONJ) were registered among Alessandria Hospital breast cancer patients. However, 9 cases were detected among 84 cases starting antiresorptive treatment without preventive visit, and 15 cases were found among 169 cases receiving dental visit before treatment beginning (15/169, 8.8%). Our preliminary data do not show the decrease of the risk of ONJ in breast cancer patients treated in the latest decade, that we expected due to generally less intensive schedules of antiresorptive drugs and due to adoption of measure of pre-treatment visit. Further evaluations have been planned to investigate if higher ONJ risk was associated to single drug (denosumab versus zoledronic acid versus pamidronate) or sequences; prolonged treatment (> 2 years); pre-existing oral disease (periodontal disease, need for tooth extraction, ill fitting dentures); and other potential predictive factors

Debate is around the optimal immunization regimen for cancer vaccines since too intense vaccination schedules may exhaust reactive lymphocytes. GX301 is a telomerase-based cancer vaccine whose safety and immunological effects were tested in a phase I trial applying an eight administrations schedule. Main objective of this study was to comparatively analyse safety and immunological response to three GX301 regimens in metastatic castration-resistant prostate cancer patients with response/disease stability after docetaxel chemotherapy. This was a multicentre, randomized, parallel-group, open-label trial registered with EudraCT (2014-000095-26) and ClinicalTrials.gov (NCT02293707, 2014). Ninety-eight patients were randomized to receive either eight (regimen 1), four (regimen 2) or two (regimen 3) vaccine administrations. Sixty-three patients were assessable for the primary immunological end-point. Vaccine-specific immune responses were evaluated by intracellular staining for IFN, elispot and cytotoxic assay at 90 and 180 days from baseline. No major side effects were recorded. A 54% overall immune responder rate was observed with 95% of patients showing at least one vaccine-specific immune response. Rate of immunological responders and number of immunizations were proportionally related, suggesting superiority of regimens 1 and 2 over regimen 3. Overall survival did not differ among regimens in both immunological responders and non-responders and was inversely associated (P = 0.002) with increase in the number of circulating CD8 + T regulatory cells at 180 days. These data indicate that GX301 cancer vaccine is safe and immunogenic in metastatic castration-resistant prostate cancer patients. Schedules with high number of administrations should be preferred in future studies due to their better immunological outcome.

ObjectiveTo evaluate the efficacy of orvepitant (10 or 30 mg given once daily, orally for 4 weeks), a neurokinin-1 receptor antagonist, compared with placebo in reducing the intensity of epidermal growth factor receptor inhibitor (EGFRI)-induced intense pruritus.DesignRandomised, double-blind, placebo-controlled clinical trial.Setting15 hospitals in Italy and five hospitals in the UK.Participants44 patients aged ≥18 years receiving an EGFRI for a histologically confirmed malignant solid tumour and experiencing moderate or intense pruritus after EGFRI treatment.Intervention30 or 10 mg orvepitant or placebo tablets once daily for 4 weeks (randomised 1:1:1).Primary and secondary outcome measuresThe primary endpoint was change from baseline in mean patient-recorded numerical rating scale (NRS) score (over the last three recordings) at week 4. Secondary outcome measures were NRS score, verbal rating scale score, Skindex-16 and Leeds Sleep Evaluation Questionnaire at each study visit (baseline, weeks 1, 4, 8); rescue medication use; EGFRI dose reduction; and study withdrawal because of intense uncontrolled pruritus.ResultsThe trial was terminated early because of recruitment challenges; only 44 of the planned 90 patients were randomised. All patients were analysed for efficacy and safety. Mean NRS score change from baseline to week 4 was −2.78 (SD: 2.64) points in the 30 mg group, −3.04 (SD: 3.06) points in the 10 mg group and −3.21 (SD: 1.77) points in the placebo group; the difference between orvepitant and placebo was not statistically significant. No safety signal was detected. Adverse events related to orvepitant (asthenia, dizziness, dry mouth, hyperhidrosis) were all of mild or moderate severity.ConclusionsOrvepitant was safe and well tolerated. No difference in NRS score between the orvepitant and placebo groups was observed at the week 4 primary endpoint. A number of explanations for this outcome are possible.Trial registration numberEudraCT2013-002763-25.

BACKGROUND:Previous studies demonstrated a predictive value of prostate-specific antigen (PSA) kinetics for treatment outcome. Our retrospective study evaluates the prognostic role of early PSA drop in metastatic castration resistant prostate cancer (mCRPC) patients receiving abiraterone acetate (AA) or enzalutamide (E).METHODS:All mCRPC patients treated with AA or E at the San Luigi Hospital in Orbassano between 2010 and 2018 and at the Ordine Mauriziano Hospital in Turin between 2014 and 2018 were included in this retrospective study. Only patients with an early PSA (measured 28-60 days after the beginning of the treatment) were included in the analysis. Patients were divided in early responders and non-early responders according to early PSA response (drop≥50% from baseline). Univariate and multivariate analyses for progression free survival (PFS) and overall survival (OS) were performed.RESULTS:Of 144 patients with early PSA value, 61 (42.4%) patients received E (docetaxel-naïve 42, post-docetaxel 19) and 83 (57.6%) received AA (docetaxel-naïve 44, post-docetaxel 39). Seventy-five (52.1%) patients achieved early PSA drop. In docetaxel-naïve setting (N.=86), median PFS was 14.9 (with early PSA drop) vs. 8.8 months (without early PSA drop, P=0.001). In post-docetaxel setting (N.=58) median PFS was 11.9 vs. 4.5 months (P<0.001). Globally, median PFS was 14.9 vs. 6.3 months in patients with and without early PSA drop, respectively (P<0.001). In docetaxel-naïve setting, patients with early PSA drop had a median OS of 39.5 vs. 18.8 months (P=0.12). In post-docetaxel setting median OS was 29.6 vs. 10.7 months (P=0.01). Comprehensively, median OS was 31.9 vs. 16.3 (P=0.002) in patients with and without early PSA drop, respectively. At multivariate analysis, early PSA drop confirmed an independent association with PFS (HR 0.21; 95% CI: 0.12-0.38, P<0.001) and OS (HR 0.25; 95% CI: 0.12-0.50, P<0.001).CONCLUSIONS:mCRPC patients treated with AA or E, in docetaxel-naïve or post-docetaxel setting, with early PSA drop had significantly better OS and PFS.

Background: Real-world data on chemotherapy-naïve patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone plus prednisone are limited, largely deriving from small retrospective studies. Methods: ABitude is an Italian, observational, prospective, multicenter study of mCRPC patients receiving abiraterone plus prednisone in clinical practice. Chemotherapy-naïve mCRPC patients were consecutively enrolled at abiraterone start (February 2016 to June 2017) and are being followed for 3 years, with evaluation approximately every 6 months. Several clinical and patients reported outcomes were examined. Results: In this second interim analysis, among 481 enrolled patients, 453 were evaluable for analyses. At baseline, the median age was 77 years and ~69% of patients had comorbidities (mainly cardiovascular diseases). Metastases were located mainly at bones and lymph nodes; 8.4% of patients had visceral metastases. During a median follow-up of 18 months, 1- and 2-year probability of radiographic progression-free survival were 73.9% and 56.2%, respectively; the corresponding rates for overall survival were 87.3% and 70.4%. In multivariable analyses, the number of bone metastases significantly affected radiographic progression-free survival and overall survival. During abiraterone plus prednisone treatment, 65% of patients had a ⩾50% prostate-specific antigen decline, and quality of life remained appreciably high. Among symptomatic patients according to the Brief Pain Inventory) (32%), scores significantly declined after 6 months of treatment. Overall, eight patients (1.7%) had serious adverse reactions to abiraterone. Conclusions: Abiraterone plus prednisone is effective and safe for chemotherapy-naïve mCRPC patients in clinical practice.

The aim of the study was to retrospectively investigate the association between chemotherapy-induced neutropenia and survival in metastatic castration-resistant prostate cancer (mCRPC) patients receiving first-line docetaxel treatment. Docetaxel-induced neutropenia is associated with better overall and progression-free survival in mCRPC. These findings support the hypothesis that chemotherapy-induced neutropenia might be a surrogate indicator of the biological activity of chemotherapy in patients with mCRPC. Background: Neutropenia is a common side effect associated with docetaxel use. We retrospectively investigated the association between chemotherapy-induced neutropenia and survival in metastatic castration-resistant prostate cancer (mCRPC) patients receiving first-line docetaxel. Patients and Methods: Metastatic castration-resistant prostate cancer patients treated with first-line docetaxel, with known neutrophils value 10 days after first administration, were included in this retrospective analysis. Neutropenia was categorized in Grade 0 to 1 (GO-1), Grade 2 to 3 (G2-3), and Grade 4 (G4). Outcome measures were progression-free survival (PFS) and overall survival (OS). Results: Eighty patients were analyzed. Median PFS was 5.4 months in patients with G0-1 neutropenia, 6.9 months with G2-3 neutropenia (hazard ratio [HR] vs. G0-1, 0.69; 95% confidence interval [Cl], 0.35-1.35; P = .27) and 9.5 months with G4 neutropenia (HR vs. G0-1, 0.30; 95% Cl, 0.16-0.57; P < .0001). Median OS was 11.6 months in patients with G0-1 neutropenia, 25.5 months in patients with G2-3 neutropenia (HR vs. G0-1, 0.36; 95% Cl, 0.16-0.80; P = .012) and 39.3 months in patients with G4 neutropenia (HR vs. G0-1, 0.19; 95% Cl, 0.09-0.41; P < .0001). In multivariate analysis, the occurrence of severe neutropenia showed a statistically significant association with OS (HR G4 vs. G0-1, 0.14; 95% Cl, 0.03-0.67; P = .013; HR G2-3 vs. G0-1, 0.42; 95% Cl, 0.11-1.57; P = .20) and PFS (HR G4 vs. G0-1, 0.28; 95% Cl, 0.09-0.86; P = .03; HR G2-3 vs. G0-1, 1.07; 95% Cl, 0.38-2.96; P = .90). Conclusion: Docetaxel-induced neutropenia is associated with better survival of mCRPC.

300 Background: Docetaxel (Doc) and Cabazitaxel (Cab) every 3 weeks with daily prednisone are standard first and second line chemotherapies in mCRPC. In daily practice, many mCRPC pts are aged > 65 years and around 20% are aged > 75years. MATuRITY registry shows that taxanes therapy provides EP with increased chances of surviving even in case of frailty. EP unfit due to their comorbidities are at risk of AE related to the chemo-treatment, so an appropriate adjustment of the dosage and schedule should be take into account. According to SIOG guidelines, G-8 Screening Tool represents a key tool to identify a suitable subset of EP able to receive cab. Methods: WeCabE enrolled mCRPC EP ≥ 70 and < 85 years, G8 Score 8-14, PS 0-2. Cab was administered at a dose of 8mg /m2 (10mg/m2 if well tolerated) for 4 out 5 weeks Use of G-CSF was allowed. Median PFS, primary endpoint, was evaluated according to PCWG-2. Secondary endpoints were: PSA Response, ORR, OS, Safety, Geriatric assessment (Minimal Data Set according with Elderly Task Force EORTC) on outcomes. PSA response, safety, impact of the treatment on pain and G8 score pre and post cab were analysed. Results: At time of this analysis 14 EP enrolled in WeCabE were analysed. Median age was 78 years, 35.7% of pts were 80-85 years. Median number of cycles received, in pts who ended treatment was 4. Overall 55.6% of pts reached a PSA response while 33.3% achieved a stability. 42.8% of pts ended therapy without a worsening/rising of symptoms, 42.8% and 14.4% showed, respectively, mild and severe pain at end of cab. G8 best score improvement during treatment was 1.28 (median). The most common AE G 3-4 was fatigue (20%) while G1-2 toxicities were diarrhea (40%) and fatigue (60%). Only one pt experienced neutropenia and anemia G3-4. Conclusions: These preliminary results confirm the usefulness of G8 tool to identify elderly mCRPC pts suitable to receive chemotherapy. It suggests that weekly cabazitaxel, in elderly mCRPC, is effective including in very old pts ( > 80 ), with a manageable safety profile. Additional results will be presented at ASCO GU meeting. Trial partially supported by Sanofi Genzyme Clinical trial information: 2014-001647-20.

209 Background: Prostate cancer affects mainly elderly patients (pts) that have different comorbidities. AA is a selective androgen synthesis inhibitor that showed the efficacy in either chemotherapy (CT) naive pts or those pretreated with docetaxel. Its oral administration and good tolerability make it a manegeable treatment for elderly mCRPC pts. Methods: We collected retrospectively data regarding mCRPC pts aged ≥75 years treated with AA in 13 Italian Centers since April 2013. The median age was 79 years (r. 75-90) with 48% of pts being octagerians. Post CT pts had more extensive disease, higher baseline PSA and ECOG PS. Nearly all the pts had comorbidities, the most frequent being hypertension present in 146 pts (58%), 43 pts (17%) had diabetes type II. We evaluated duration of the AA treatment, overall response rate (ORR), 50% PSA decline, time to progression (TTP) and overall survival (OS). We reported all toxicities observed. Results: A total of 252 pts ,147 pre treated with docetaxel and 105 chemo naive, were included. Median duration of treatment with AA was 8,6 months in post CT and 11,5 in CT naive pts. ORR was 35,3% in pre docetaxel and 27,4% in post docetaxel group. 64 pts (65%) and 51 pts (46%) obtained 50% PSA reduction in pre and post docetaxel group, respectively. Median TTP was 8,6 in post docetaxel and 11,9 in CT naive pts. We observed a median OS of 13,8 months in post CT group while for CT naive pts data were not yet mature. AA was well tolerated with only 8 pts (3,2%) who discontinued treatment due to toxicity, while in 4 pts (1,6%) temporary dose reductions were performed. The most frequent G3 toxicities were hypertension and liver toxicity with 4 pts (1,6%) and 5 pts (2%), respectively. After progressing on AA, 85 pts (34%) received at least one subsequent treatment. 40 pts (15,9%) are still on treatment with AA. Conclusions: Even if almost all the pts reported comorbidities at AA start and 72 pts (28,6%) had PS ECOG 2, only a small proportion of them discontinued the treatment due to toxicity confirming that AA is well tolerated and efficient treatment also for elderly patients.

Background: The neutrophil-to-lymphocyte ratio (NLR), a measure of systemic inflammatory response, has been associated with poor outcome in several solid tumors, including prostate cancer. We retrospectively investigated the prognostic role of pretreatment NLR in metastatic castration-resistant prostate cancer (mCRPC) patients treated with first-line docetaxel.Methods: All CRPC patients treated with first-line docetaxel at two Italian institutions, with available data about baseline neutrophil and lymphocyte values, were included in this retrospective analysis. Patients were divided in two groups according to NLR ratio (low NLR:3; high NLR:>3). Outcome measures were progression-free (PFS) and overall survival (OS), measured from the start of docetaxel treatment. Univariate and multivariate analysis (adjusting for baseline prostate-specific antigen, alkaline phosphatase, lactate dehydrogenase, hemoglobin, albumin, performance status, use of opioids and presence of visceral disease) were performed.Results: One hundred and seventy-nine patients treated between 2004 and 2016 were analyzed and 110 had information about pretreatment NLR. Forty-six patients (42%) had low NLR and 64 (58%) had high NLR. Median PFS was 8.8 months in patients with low NLR versus 7.3 months in those with high NLR [hazard ratio (HR) 1.12, 95% confidence interval (CI) 0.75-1.69, p=.58]. Median OS was 34.9 months in patients with low NLR versus 20.2 months in those with high NLR (HR 1.85, 95% CI 1.07-3.19, p=.02). At multivariate analysis, NLR confirmed an independent impact on OS (HR 3.16, 95% CI 1.50-6.65, p=.002).Conclusion: In this retrospective series, metastatic CRPC patients who started first-line docetaxel with a low pretreatment NLR had a significantly better survival. In addition to known prognostic factors, NLR can be useful to improve prognostic evaluation of patients in this setting.

Osteonecrosis of the jaw (ONJ) associated with the use of bisphosphonates has been rarely reported in metastatic renal cell cancer (RCC) patients. Since the introduction of combined therapies consisting of nitrogen-containing bisphosphonates (NBPs) and targeted agents, an increasing number of RCC patients were reported to develop ONJ, suggesting that therapeutic angiogenesis suppression might increase the risk of ONJ in NBPs users. We performed a multicenter retrospective study and reviewed literature data to assess the occurrence and to investigate the nature of ONJ in RCC patients taking NBPs and targeted agents. Nine Italian Centers contributed to the data collection. Patients with exposed and nonexposed ONJ were eligible for the study if they had been taking NBPs and were receiving targeted agents at the time of ONJ diagnosis. Forty-four RCC patients were studied. Patients were mostly male (82%), with a median age of 63 years (range, 45-85 years). Zoledronic acid (93%) and sunitinib (80%) were the most frequently used NBP and antiangiogenic agent, respectively. Other agents included Pamidronate, ibandronate, sorafenib, bevacizumab, mammalian target of rapamycin inhibitors. Forty-nine sites of ONJ were encountered, with the mandible being the preferred site of ONJ (52%); both jaws were affected in 5 cases (12%). The most common precipitating event was dental/periodontal infection (34%), followed by tooth extraction (30%). Oral triggers of ONJ were missing in 10 cases (23%). This unexpectedly high number of ONJ cases, in comparison with literature data, suggests that frequency of ONJ in RCC patients might be largely underestimated and suggests a potential role for targeted agents in the incremental risk of ONJ.

Gross cystic disease (GCDB) is a breast benign condition predisposing to breast cancer. Cryopreserved sera from GCDB patients, some of whom later developed a cancer (cases), were studied to identify potential risk markers. A MALDI-TOF mass spectrometry analysis found several complement C3f fragments having a significant increased abundance in cases compared to controls. After multivariate analysis, the full-length form of C3f maintained a predictive value of breast cancer risk. Higher levels of C3f in the serum of women affected by a benign condition like GCDB thus appears to be correlated to the development of breast cancer even 20 years later.Biological significanceIncreased complement system activation has been found in the sera of women affected by GCDB who developed a breast cancer, even twenty or more years later. C3f may predict an increased breast cancer risk in the healthy population and in women affected by predisposing conditions. (C) 2013 Elsevier B.V. All rights reserved.

We previously demonstrated that high serum enterolactone levels are associated with a reduced incidence of breast cancer in healthy women. The present study was aimed at investigating whether a similar association might be found between serum enterolactone levels and the mortality of women with early breast cancer. The levels of enterolactone in cryopreserved serum aliquots obtained from 300 patients, operated on for breast cancer, were measured using a time-resolved fluoro-immunoassay. Levels were analyzed in respect to the risk of mortality following surgery. Cox proportional hazard regression models were used to check for prognostic features, to estimate hazard ratios for group comparisons and to test for the interaction on mortality hazards between the variables and enterolactone concentrations. The Fine and Gray competing risk proportional hazard regression model was used to predict the probabilities of breast cancer-related and breast cancer-unrelated mortalities. At a median follow-up time of 23 years (range 0.6–26.1), 180 patients died, 112 of whom died due to breast cancer-related events. An association between a decreased mortality risk and enterolactone levels ≥10 nmol/l was found in respect to both all-cause and breast cancer-specific mortality. The difference in mortality hazards was statistically significant, but it appeared to decrease and to lose significance after the first 10 years, though competing risk analysis showed that breast cancer-related mortality risk remained constantly lower in those patients with higher enterolactone levels. Our findings are consistent with those of most recent literature and provide further evidence that mammalian lignans might play an important role in reducing all-cause and cancer-specific mortality of the patients operated on for breast cancer.

First, to evaluate whether the benefits of combined chemotherapy (CT) and Tamoxifen (T), previously documented in the GROCTA-01 Trial, were long-lasting and, second, to show whether ER or PgR levels could allow the identification of the patients who could benefit from T alone. 504 node-positive, ER-positive, women were randomly assigned to ten CT courses or to 5 years of T or to the combination of the two (CTT). Disease-free (DFS) and overall survival (OS) were the primary trial-endpoints. DFS data were updated in 75% of the patients and S data in 95% of them. Cox regression models were used to check for prognostic features to estimate hazard ratios for treatment comparisons and to test for possible interaction between variables and treatment effects. Interactions between treatments and ER or PgR median levels were studied with the sub-population treatment effect pattern plot (STEPP) methodology. After a median follow-up time of 21 years, the DFS and OS benefits, previously favouring T over CT, continued to be observed, even though they were more evident in the first 6–7 years. The CTT advantages of DFS and OS over T alone were also confirmed. However, the additional benefit was limited to the first 10–12 years as S curves crossed over afterwards. After STEPP analysis, neither ER nor PgR concentrations fully discriminated the patients who could benefit from T alone. Even after such a long follow-up time, we have demonstrated that T is an effective alternative to CT for node-positive, ER-positive, breast cancer patients, regardless of their actual menopausal status, and that the additional benefit, especially on late survival, provided by the addition of CT to this anti-oestrogen, was minimal.

Objective: Breast cancer patients with >3 involved nodes (N+) have a poor outcome. Chemotherapy (CT), alone or combined with endocrine therapy (ET) in hormone receptor (HOR)-positive patients, is the standard for these women. However, there are still questions surrounding the optimal adjuvant CT regimen. Methods: 244 patients with >3 N+ were randomized to receive either four 3-weekly courses of epirubicin (E: 100 mg/m2, day 1) followed by four 4-weekly cycles of cyclophosphamide, methotrexate and 5-fluorouracil (CMF: 600, 40, 600 mg/m2, days 1, 8: n = 122) or four 3-weekly courses of paclitaxel (T: 175 mg/m2, day 1) followed by four 3-weekly cycles of epirubicin and vinorelbine (E: 75 mg/m2, day 1; V: 25 mg/m2, days 1, 8: n = 122). After CT, tamoxifen (plus an LH-RH analog in menstruating women) was given to all HOR-positive patients over a period of 5 years. Overall survival (OS) was the primary end point. Relapse-free survival (RFS) and toxicity were secondary end points. Results: At a median follow-up time of 102 months (range 3–146), OS and RFS did not differ significantly between groups (E-CMF vs. T-EV: OS, HR 0.94, 95% CI 0.59–1.48, p = 0.8; RFS, HR 0.86, 95% CI 0.57–1.29, p = 0.45). The lack of any difference between assigned treatments was confirmed by multivariate analysis (E-CMF vs. T-EV: RFS, HR 0.98, 95% CI 0.64–1.48, p = 0.9). The 2 regimens showed different toxicity profiles. In fact, significantly more women assigned to E-CMF were affected by stomatitis (p = 0.001) while significantly more women in the T-EV group developed peripheral neuropathy (p < 0.0001) and musculoskeletal disorders (p < 0.0001). However, side effects were moderate and manageable and no toxic death occurred in either arm of the study. Conclusions: T-EV was safe and moderately toxic but was not superior to E-CMF.

Objectives: Biological markers that reliably predict clinical and pathological response to primary systemic therapy may have considerable clinical potential; this study evaluated response compared to expression of ER, PgR and Her2, grading and Ki-67 proliferation index before and after neoadjuvant chemotherapy in patients with locally advanced breast cancer (LABC). Patients and Methods: Fifty-five patients received neoadjuvant chemotherapy for LABC. The incidence of clinical and pathological responses was assessed with respect to basal clinical stage, absent/low vs. high ER and PgR status, low vs. high proliferation index, grading and Her2 overexpression. Results: Overall, 30 patients (54%) underwent downstaging of their primary tumor; pathological complete remission was observed in only one patient with Her2 positive breast tumor. Patients with pre-treatment Ki-67 >20%, Her2 overexpression, T2b/T3 vs. T4 clinical stage achieved higher response rate. Conclusion: The future of neoadjuvant therapy lies in tailoring treatment to individual patients by identifying response predictors; although the number of patients reported is small, this study confirms that clinical stage at diagnosis, Ki-67 reduction and Her2 overexpression are predictive of tumor response to neoadjuvant regimens.

Objectives: This paper reviews the status of the art concerning medical treatment of advanced renal cell cancer (RCC) and new therapeutic options, namely, targeted therapies.Methods: The review was based on the most recent and relevant papers appearing in the literature.Results: Cytokines, including interferon-alpha (IFN-alpha) and interleukin 2 (IL-2) represent the treatment of choice for most RCC patients. High-dose IL-2 provides a limited but clinically relevant proportion of patients with durable response benefit. Although hormone therapy has only historical value, cytotoxic chemotherapy is an option for patients who become refractory to immunotherapies. Results achieved with cytotoxic drugs are usually poor, though 5-fluororacil, capecitabine, and gemcitabine have moderate activity coupled with manageable toxicity. Growing understanding of RCC biology has provided new targets for biologic therapies. Antiangiogenic drugs, which include monoclonal antibodies against vascular endothelial growth factor (VEGF), such as bevacizumab, or small molecules targeting VEGF receptors, such as SU011248, PTK787/2K22254, and BAY 43-9006, look promising, either alone or in combination with cytokines or cytotoxic drugs.Conclusions: The management of patients with metastatic RCC is still frustrating because the most of these patients die of their disease. Although a limited subset of patients can experience clinically meaningful benefit from IL-2 or IFN-alpha therapy and a limited benefit, if any, can be achieved in these patients with conventional chemotherapy, there is no other proven effective therapy for patients who do not respond or who relapse after cytokine-based treatment. Better understanding of RCC biology has provided insights on relevant signal transduction pathways, genetic mutations, and tumour susceptibilities to innate immune response resulting in novel treatment strategies that promise to affect the natural history of this lethal disease. (c) 2006 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Today hormone therapies still aim at interfering with the mitogenic action of sexual hormones. Basically this aim can be attained through the inhibition of the synthesis of steroid hormones. In this way target cells are spared the trophic stimulus represented by those hormones (“ablative hormone thera-py”). Otherwise, it is possible to affect the link between sexual hormones and their receptors, and to interfere with one or more stages of the transcription process (“competitive hormone therapy”).