Oncology RSS : Gourt

Medical Director, Nationally Recognized Cancer Center, Southern Metro, #3339 :: Louisiana :: Timeline Recruiting

Join a medical center in providing multispecialty cancer care that has achieved the gold standard for outstanding cancer programs. Become a vital part of a National Cancer Institute Community Cancer

Redding - Northern California :: California :: California Physician Opportunities

MR-1012 Oncology opportunity for Northern CA Metro Located at the top of the San Joaquin Valley near major ski resorts and fantastic water sports California's larger lakes, Large

Call for Information :: Texas :: Inhouse Physician Recruiters Network

The In-House Physician Recruiter Network, composed of over 500 hospital recruiters, represents over 10,000 hospitals and clinics. Our Network's special feature is to showcase outstanding physicians (who

Call for Information :: North Dakota :: Inhouse Physician Recruiters Network

Knoxville Community :: Tennessee :: Sunbelt Management Associates

Oncology Group looking to add a Hematologist/Oncologist to join their group. They are a growing group with 2 different locations. 350,000.00 base plus bonus Employment Sign-on bonus Located in

Call for location :: Missouri :: Medical Doctor Associates

Freestanding Cancer Center in Missouri is looking for a medical oncologist to join the practice full time. Patient load is shared and the practice offers a weekly work schedule of 5:3 (work 3-5 weeks

Call for location :: Kansas :: Medical Doctor Associates

Great perm opportunity for a board certified MO/HEM in small town in Kansas. Wonderful opportunity to build your own solo practice within a small community. Competitive salary. If interested please contact

Not Disclosed :: Ohio :: Locum Medical Group

A small, single specialty group of Hematologists and Oncologists are searching for a third Board Certified or Board Eligible Hem/Onc to join their group. Their practice is located approximately 1 hour

Ronceverte :: West Virginia :: Community Health Systems

Seeking an Oncologist for Greenbrier Valley Medical Center. Offering a one-year income guarantee, a sign-on bonus, and relocation expenses; to either join a private practice or a mult-practice opportunity.

Long Beach :: California :: Long Beach Memorial Medical Center

Seeking a Board-Certified Breast Medical Oncologist who will provide medical direction, coordination and oversight for a leading, hospital-based Southern California breast center. The incumbent will

Northeast :: Oregon :: Fidelis Partners

ONCOLOGY 300 DAYS OF SUNSHINE, PACIFIC NORTHWEST $400K TO START JOINT VENTURE OPPORTUNITY Be a hospital employee of a successful healthcare system or start your own practice * Your choice: become

Portland :: Oregon :: Providence Health & Services

Portland, Oregon High-end clinical practice with hematology and heme-malignancies focus. The 13 members of the Oncology/Hematology Group of the Providence Cancer Center in Portland are seeking an exceptional

Northern :: California :: Oncology - $400,000 Potential -Northern California

NORTHERN CALIFORNIA HEMATOLOGY-ONCOLOGY NO HMOS/ NO CAPITATION If you have dreamed of joining a group where patient care comes first, please consider this opportunity: $300,000 to $350,000

Olympia :: Washington :: Providence Health & Services

Olympia, Washington -- Providence Physician Network has a unique opportunity for a BE/BC Oncology Hospitalist to join our employed Oncology team at Providence St. Peter Hospital in Washington's capital

Newberg :: Oregon :: Providence Health & Services

Newberg, Oregon -- Providence Newberg Medical Center has an immediate opening for an experienced BE/BC Oncologist to join us in this beautiful semi-rural suburb of Portland. Ideal candidate will have

Spokane :: Washington :: Providence Health & Services

Spokane, Washington: Providence Health & Services is partnering with a well-respected private practice to bring an excellent BE/BC Medical Oncologist to serve the community. Group is affiliated with

Enid :: Oklahoma :: Universal Health Services, Inc.

Oncology Private Practice - Outstanding Personal and Professional Growth Opportunity St. Marys Regional Medical Center is assisting in the recruitment of a new Oncologist to the community. This

Yuma :: Arizona :: Yuma Regional Medical Center

Outstanding opportunity for an oncologist seeking quality of medicine and quality of life. Seeking BC/BE Oncologist to join a well established and well respected medical oncology practice in the desert

in this issue

Now's the time to find biomarkers on purpose

Treatment of cancer with oral drugs: a position statement by the Spanish Society of Medical Oncology (SEOM)

Darwin, medicine and cancer

‘Nothing in biology makes sense except in the light of evolution’! So said Theodore Dobzhansky. It is extraordinary how little Darwinism and post-Darwinian evolutionary science has penetrated medicine despite the fact that all biology is built upon its foundations. Randy Nesse, one of the fathers of Darwinian medicine, recently observed that doctors ‘know the facts but not the origins’. Clearly, then, in this auspicious year—200 years since Charles Darwin's birth and 150 years since the first edition of the Origin of Species—it is time to reconsider Darwin's legacy to medicine and to invite evolution back into the biomedical fold. Here, we consider the legacy of Darwin and the contribution of the other great evolutionists such as Ernst Mayr to cancer and medicine.

Communication skills training in oncology: a position paper based on a consensus meeting among European experts in 2009

Background: Communication in cancer care has become a major topic of interest. Since there is evidence that ineffective communication affects both patients and oncology clinicians (physicians and nurses), so-called communication skills trainings (CSTs) have been developed over the last decade. While these trainings have been demonstrated to be effective, there is an important heterogeneity with regard to implementation and with regard to evidence of different aspects of CST. Methods: In order to review and discuss the scientific literature on CST in oncology and to formulate recommendations, the Swiss Cancer League has organised a consensus meeting with European opinion leaders and experts in the field of CST, as well as oncology clinicians, representatives of oncology societies and patient organisations. On the basis of a systematic review and a meta-analysis, recommendations have been developed and agreed upon. Results: Recommendations address (i) the setting, objectives and participants of CST, (ii) its content and pedagogic tools, (iii) organisational aspects, (iv) outcome and (v) future directions and research. Conclusion: This consensus meeting, on the basis of European expert opinions and a systematic review and meta-analysis, defines key elements for the current provision and future development and evaluation of CST in oncology.

Pharmacological management of gastrointestinal stromal tumours: an update on the role of sunitinib

The efficacy and tolerability of the receptor tyrosine kinase inhibitor, sunitinib malate, have been demonstrated in phase I–III clinical trials of patients with imatinib-resistant or imatinib-intolerant gastrointestinal stromal tumours (GIST) as well as in a worldwide expanded-access study and in a continuous daily dosing (CDD) trial. Tumour genotype may have a significant influence on the activity of sunitinib in patients with imatinib-resistant GIST. Sunitinib activity was observed across different GIST genotypes and particularly in patients with wild-type and KIT exon 9 mutations (all relatively resistant to standard-dose imatinib) and in patients with secondary KIT exons 13 and 14 mutations. Adverse events with sunitinib were generally mild to moderate and easily managed by dose reduction, dose interruption or standard supportive measures. Treatment discontinuation can be avoided in most patients by close monitoring before and during treatment with appropriate adverse event management as necessary. The correlation between treatment exposure and clinical response is prompting the search for new approaches to treatment optimisation to ensure that patients derive maximum benefit from sunitinib therapy, including dose adjustments based on blood testing to ensure optimal drug exposure, and the use of the alternative CDD regimen to avoid treatment interruption.

A multicentre phase II gene expression profiling study of putative relationships between tumour biomarkers and clinical response with erlotinib in non-small-cell lung cancer

Background: Identification of appropriate markers for predicting clinical benefit with erlotinib in non-small-cell lung cancer (NSCLC) may be able to guide patient selection for treatment. This open-label, multicentre, phase II trial aimed to identify genes with potential use as biomarkers for clinical benefit from erlotinib therapy. Methods: Adults with stage IIIb/IV NSCLC in whom one or more chemotherapy regimen had failed were treated with erlotinib (150 mg/day). Tumour biopsies were analysed using gene expression profiling with Affymetrix GeneChip® microarrays. Differentially expressed genes were verified using quantitative RT–PCR (qRT–PCR). Results: A total of 264 patients were enrolled in the study. Gene expression profiles found no statistically significant differentially expressed genes between patients with and without clinical benefit. In an exploratory analysis in responding versus nonresponding patients, three genes on chromosome 7 were expressed at higher levels in the responding group [epidermal growth factor receptor (EGFR), phosphoserine phosphatase (PSPH) and Rap guanine nucleotide exchange factor 5 (RAPGEF5)]. Independent quantification using qRT–PCR validated the association between EGFR and PSPH overexpression, but not RAPGEF5 overexpression, and clinical outcome. Conclusions: This study supports the use of erlotinib as an alternative to chemotherapy for patients with relapsed advanced NSCLC. Genetic amplification of the EGFR region of chromosome 7 may be associated with response to erlotinib therapy.

Co-expression of PDGF-B and VEGFR-3 strongly correlates with lymph node metastasis and poor survival in non-small-cell lung cancer

Background: Platelet-derived growth factors (PDGFs) and vascular endothelial growth factors and their receptors [platelet-derived growth factor receptors (PDGFRs) and vascular endothelial growth factor receptors (VEGFRs)] are related to both angiogenesis and lymphangiogenesis and are important targets in new cancer treatment strategies. We aimed to study the PDGFs/PDGFRs and correlations with lymph node metastasis (LNM) and investigate the prognostic impact of the co-expression of PDGF-B and VEGFR-3 and its correlation with LNM. Patients and methods: Tumor tissue samples from 335 resected patients with stage I–IIIA non-small-cell lung cancer (NSCLC) were obtained and tissue microarrays were constructed from duplicate cores of tumor cells and tumor-related stroma from each specimen. Immunohistochemistry was used to evaluate the expression of the molecular markers PDGF-A, PDGF-B, PDGF-C, PDGF-D, PDGFR-, PDGFR-β, VEGFR-3 and D2-40. Results: There were 232 N0 and 103 N+ patients (76 N1 and 27 N2). In multivariate analyses, high tumor cell PDGF-A expression (P = 0.017) correlated with LNM. Tumor cell co-expression of VEGFR-3 and PDGF-B correlated with nodal metastasis and was an independent indicator of poor prognosis (hazard ratio 4.8, confidence interval 95% 2.80–8.31, P < 0.001). Conclusion: Tumor cell PDGF-A expression correlates with LNM, and the co-expression of PDGF-B and VEGFR-3 is strongly associated with poor survival in NSCLC patients.

The strength of female sex as a prognostic factor in small-cell lung cancer: a pooled analysis of chemotherapy trials from the Manchester Lung Group and Medical Research Council Clinical Trials Unit

Background: Previous studies reported that women survive longer than men, but experience greater toxicity, when treated for small-cell lung cancer (SCLC). Methods: Individual patient data from six randomized phase II/III chemotherapy trials, from the Manchester Lung Group and UK Medical Research Council, were pooled for analysis. End points included overall survival, response rate, toxicity, dose intensity (DI) and transfusion rates. Results: Of 1707 patients analyzed, 44% were women. At baseline, women had poorer performance status (PS) (57% versus 67% Eastern Cooperative Oncology Group PS 0–1/Karnofsky PS 80–100, P = 0.0004) and more were of normal weight or underweight (57% versus 48%, P = 0.003), but fewer were anemic (25% versus 62%, P < 0.0001). Response rates between women and men were similar (77% versus 76%, P = 0.64). In univariate [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.76–0.96, P = 0.006] and multivariate (HR 0.88, 95% CI 0.79–0.99, P = 0.04) analyses, female sex predicted for longer survival. Women experienced more grade 3/4 emesis (18% versus 9%, P < 0.0001) and grade 3/4 mucositis (13% versus 8%, P = 0.005) than men. There were no differences in DI, infections, transfusions or treatment-related deaths. Conclusion: Data from >1700 patients in randomized SCLC chemotherapy trials confirm that women survive modestly longer than men but may experience greater toxicity.

AIB1 is a predictive factor for tamoxifen response in premenopausal women

Background: Clinical trials implicate the estrogen receptor (ER) coactivator amplified in breast cancer 1 (AIB1) to be a prognostic and a treatment-predictive factor, although results are not unanimous. We have further investigated this using a controlled randomised trial of tamoxifen versus control. Materials and methods: A total of 564 premenopausal women were entered into a randomised study independent of ER status. Using a tissue microarray, AIB1 and ER were analysed by immunohistochemistry. Results: AIB1 scores were obtained from 349 women. High AIB1 correlated to factors of worse prognosis (human epidermal growth factor receptor 2, Nottingham histological grade 3, and lymph node metastases) and to ER negativity. In the control arm, high AIB1 was a negative prognostic factor for recurrence-free survival (RFS) (P = 0.02). However, ER-positive patients with high AIB1 responded significantly to tamoxifen treatment (P = 0.002), increasing RFS to the same level as for systemically untreated patients with low AIB1. Although ER-positive patients with low AIB1 had a better RFS from the beginning, this was not further improved by tamoxifen (P = 0.8). Conclusions: In the control group, high AIB1 was a negative prognostic factor. However, ER-positive patients with high AIB1 responded significantly to tamoxifen. This implicates high AIB1 to be an independent predictive factor of improved response to tamoxifen and not, as has previously been discussed, a factor predicting tamoxifen resistance.

Adverse prognostic value of peritumoral vascular invasion: is it abrogated by adequate endocrine adjuvant therapy? Results from two International Breast Cancer Study Group randomized trials of chemoendocrine adjuvant therapy for early breast cancer

Background: Peritumoral vascular invasion (PVI) may assist in assigning optimal adjuvant systemic therapy for women with early breast cancer. Patients and methods: Patients participated in two International Breast Cancer Study Group randomized trials testing chemoendocrine adjuvant therapies in premenopausal (trial VIII) or postmenopausal (trial IX) node-negative breast cancer. PVI was assessed by institutional pathologists and/or central review on hematoxylin–eosin-stained slides in 99% of patients (analysis cohort 2754 patients, median follow-up >9 years). Results: PVI, present in 23% of the tumors, was associated with higher grade tumors and larger tumor size (trial IX only). Presence of PVI increased locoregional and distant recurrence and was significantly associated with poorer disease-free survival. The adverse prognostic impact of PVI in trial VIII was limited to premenopausal patients with endocrine-responsive tumors randomized to therapies not containing goserelin, and conversely the beneficial effect of goserelin was limited to patients whose tumors showed PVI. In trial IX, all patients received tamoxifen: the adverse prognostic impact of PVI was limited to patients with receptor-negative tumors regardless of chemotherapy. Conclusion: Adequate endocrine adjuvant therapy appears to abrogate the adverse impact of PVI in node-negative disease, while PVI may identify patients who will benefit particularly from adjuvant therapy.

Association between gain-of-function mutations in PIK3CA and resistance to HER2-targeted agents in HER2-amplified breast cancer cell lines

Background: The mechanism of resistance to human epidermal growth factor receptor 2 (HER2)-targeted agents has not been fully understood. We investigated the influence of PIK3CA mutations on sensitivity to HER2-targeted agents in naturally derived breast cancer cells. Materials and methods: We examined the effects of Calbiochem (CL)-387,785, HER2 tyrosine kinase inhibitor, and trastuzumab on cell growth and HER2 signaling in eight breast cancer cell lines showing HER2 amplification and trastuzumab-conditioned BT474 (BT474-TR). Results: Four cell lines with PIK3CA mutations (E545K and H1047R) were more resistant to trastuzumab than the remaining four without mutations (mean percentage of control with 10 µg/ml trastuzumab: 58% versus 92%; P = 0.010). While PIK3CA-mutant cells were more resistant to CL-387,785 than PIK3CA-wild-type cells (mean percentage of control with 1 µM CL-387,785: 21% versus 77%; P = 0.001), CL-387,785 retained activity against BT474-TR. Growth inhibition by trastuzumab and CL-387,785 was more closely correlated with changes in phosphorylation of S6K (correlation coefficient, 0.811) than those of HER2, Akt, or ERK1/2. Growth of most HER2-amplified cells was inhibited by LY294002, regardless of PIK3CA genotype. Conclusions: PIK3CA mutations are associated with resistance to HER2-targeted agents. PI3K inhibitors are potentially effective in overcoming trastuzumab resistance caused by PIK3CA mutations. S6K phosphorylation is a possibly useful pharmacodynamic marker in HER2-targeted therapy.

Daidzein induces MCF-7 breast cancer cell apoptosis via the mitochondrial pathway

Background: In order to study the anticancer effects and cellular apoptosis pathways induced by daidzein. Materials and methods: We used the human MCF-7 breast cancer cell line as a model and examined the apoptosis by Hoechst–propidium iodide staining fluorescence imaging and flow cytometry. Results: Our data indicated that daidzein induces antiproliferative effects in a concentration- and time-dependent manner. We demonstrated that daidzein-induced apoptosis in MCF-7 cells was initiated by the generation of reactive oxygen species (ROS). Furthermore, we showed that this daidzein-induced ROS generation was accompanied by disruption of mitochondrial transmembrane potential, down-regulation of bcl-2, and up-regulation of bax, which led to the release of cytochrome C from the mitochondria into the cytosol, which, in turn, resulted in the activation of caspase-9 and caspase-7, and ultimately in cell death. The induction of the mitochondrial caspase-dependent pathway was confirmed by pretreatment with pan-caspase inhibitor z-VAD-fmk and antioxidant N-acetyl-L-cysteine. Conclusion: Accordingly, daidzein could induce breast cancer cell apoptosis through the mitochondrial caspase-dependent cell death pathway.

North Central Cancer Treatment Group (NCCTG) N0432: phase II trial of docetaxel with capecitabine and bevacizumab as first-line chemotherapy for patients with metastatic breast cancer

Background: Docetaxel (T; Taxotere) with capecitabine (X) is active against metastatic breast cancer (MBC); bevacizumab (BV) has demonstrated efficacy with taxanes in the first-line setting. This study was conducted to assess the safety and efficacy of TX-BV in patients with MBC. Patients and methods: In this single-arm, multicenter phase II study, patients received first-line bevacizumab 15 mg/kg and docetaxel 75 mg/m2 on day 1 and capecitabine 825 mg/m2 twice per day on days 1–14 every 21 days. Primary and secondary end points were tumor response rate (RR), overall survival (OS), progression-free survival (PFS), and toxicity. Results: A total of 45 assessable patients received TX-BV for a median of seven cycles. Two complete and 20 partial responses were observed (overall RR 49%); nine patients had stable disease >6 months, for a clinical benefit rate of 69%. Median response duration was 11.8 months. Median OS and PFS were 28.4 and 11.1 months, respectively. Grade 3/4 adverse events included hand–foot syndrome (29%), fatigue (20%), febrile neutropenia (18%), and diarrhea (18%). In cycles 3–10, median dose levels of docetaxel and capecitabine were 60 mg/m2 and 660 mg/m2, respectively. Conclusion: TX-BV demonstrated significant activity; dose modifications were required to manage drug-related toxic effects.

An open-label, randomized phase II study of adecatumumab, a fully human anti-EpCAM antibody, as monotherapy in patients with metastatic breast cancer

Background: High-level expression of epithelial cell adhesion molecule (EpCAM) is associated with unfavorable prognosis in breast cancer. This study was designed to investigate two doses of the fully human IgG1 anti-EpCAM antibody adecatumumab (MT201) in patients with metastatic breast cancer (MBC). Methods: A total of 109 patients were stratified into high- and low-level EpCAM expression by immunohistochemical staining of primary tumors and subsequently randomly assigned to receive monotherapy with either high- (6 mg/kg every two weeks (q2w)) or low-dose adecatumumab (2 mg/kg/ q2w) until disease progression. Results: No complete or partial tumor responses could be confirmed by central RECIST assessment. The probability for tumor progression was significantly lower in patients receiving high-dose adecatumumab and expressing high levels of EpCAM (hazard ratio 0.43; P = 0.0057 versus low dose and low EpCAM). Three of 18 patients with highest EpCAM expression treated with adecatumumab developed new metastases up to week 6, compared with 14 of 29 patients with low EpCAM. Most frequent treatment-related adverse events (high dose/low dose) were chills (59%/20%), nausea (55%/18%), fatigue (39%/23%) and diarrhea (43%/7%). Conclusions: Single-agent adecatumumab shows dose- and target-dependent clinical activity in EpCAM-positive MBC, albeit no objective tumor regression. Further investigation of adecatumumab in patients with EpCAM-overexpressing tumors and lower tumor burden is warranted.

A randomized placebo-controlled study of tamoxifen after adjuvant chemotherapy in premenopausal women with early breast cancer (National Cancer Institute of Canada--Clinical Trials Group Trial, MA.12)

Background: In the early 1990s, the role of adjuvant tamoxifen in premenopausal women with early breast cancer (EBC) was not established. Similarly, optimum timing relative to adjuvant chemotherapy and efficacy of tamoxifen in hormone receptor-negative tumors were unclear. Patients and methods: Premenopausal women with EBC, any hormone receptor status, after surgery received standard adjuvant chemotherapy [doxorubicin (adriamycin)/cyclophosphamide, cyclophosphamide/methotrexate/5-fluorouracil, or cyclophosphamide/epirubicin/5-fluorouracil] followed by randomization to tamoxifen or placebo for 5 years. Outcomes were overall survival (OS), disease-free survival (DFS), toxicity, and compliance with therapy. Results: Median follow-up for 672 women was 9.7 years. Multivariate analysis showed improved DFS [78.2% versus 71.3% at 5 years; hazard ratio (HR) 0.77; P = 0.056] and a trend for improved OS (86.6% versus 82.1% at 5 years; HR 0.78; P = 0.12). There was no evidence of greater benefit for the receptor-positive subgroup. Compliance with treatment was suboptimal in both arms, with 103 (31%) women on tamoxifen and 70 (21%) on placebo-stopping therapy early because of toxicity, refusal, or other choices. Conclusions: Adjuvant tamoxifen, given after chemotherapy to premenopausal women with EBC, improved 5-year DFS. Poor compliance may have reduced treatment efficacy.

Treatment and survival in breast cancer in the Eastern Region of England

Background: The reasons for variation in survival in breast cancer are multifactorial. Methods: From 1999 to 2003, the vital status of 9051 cases of invasive breast cancer was identified in the Eastern Region of England. Survival analysis was by Cox proportional hazards regression. Data were analysed separately for patients aged <70 years and those older due to differences in treatment policies. Results: Overall 5-year survival was 78%. In patients aged <70 years, significant differences in survival lost their formal significance after adjustment for detection mode and node status, although this remained close to statistical significance with some residual differences between relative hazards. There was significant negative ecological correlation between proportion with nodes positive or not examined and 9-year survival rates. Patients with estrogen receptor (ER) status unknown were at significantly higher risk of dying than ER-positive patients. There was a clear trend of increasing hazard of dying with increasing deprivation. Survival differences in women aged ≥70 years were related to whether surgery was included as part of treatment. Conclusion: This variation in treatment and survival may be attributed to lack of information, in particular nodal and ER status, thereby impacting on staging and prescription of adjuvant therapy.

A phase I study of axitinib (AG-013736) in combination with bevacizumab plus chemotherapy or chemotherapy alone in patients with metastatic colorectal cancer and other solid tumors

Background: Axitinib and bevacizumab are targeted therapies against the vascular endothelial growth factor pathway. Methods: Patients with previously treated solid tumors received axitinib (starting dose 5 mg twice daily) combined with FOLFOX plus bevacizumab (1, 2, or 5 mg/kg, cohorts 1–3, respectively), FOLFIRI (cohort 4), or FOLFOX (cohort 5). Safety and pharmacokinetics were assessed. Results: Thirty patients were enrolled (n = 16, 8, and 6 for cohorts 1–3, 4, and 5, respectively). Plasma concentrations and pharmacokinetic (PK) parameters were similar when drugs were administered alone and in various combinations. Most treatment-emergent adverse events (AEs) were mild to moderate and clinically manageable (most common: nausea, fatigue, diarrhea, anorexia, hypertension). Two of the four patients receiving axitinib with FOLFOX plus 5 mg/kg bevacizumab experienced dose-limiting toxicity (DLT) of inability to resume treatment for 14 days following treatment interruption (associated AE: hypertension); the maximum tolerated dose of bevacizumab in this combination was 2 mg/kg. No DLTs occurred with axitinib plus FOLFIRI or FOLFOX. Ten patients had RECIST-confirmed partial tumor responses (objective response rate: 33.3%). Conclusion: Axitinib is well tolerated in combination with FOLFOX, FOLFIRI, or FOLFOX plus 2 mg/kg bevacizumab. PK interactions appear to be absent.

A phase IB study of ABT-751 in combination with docetaxel in patients with advanced castration-resistant prostate cancer

Background: This study investigated the safety, pharmacokinetics (PK) and clinical antitumor activity of ABT-751, a novel sulfonamide antimitotic and vascular disrupting agent, in combination with docetaxel (Taxotere) in patients with castration-resistant prostate cancer (CRPC). Patients and methods: Patients received docetaxel (60–75 mg/m2) i.v. on day 1 and ABT-751 (100–200 mg) orally daily for 14 days, repeated every 3 weeks for up to 10 times on four escalating dose levels (DLs). Results: Thirty-two patients received a median of 8.5 treatment cycles (range 1–10). One of six patients on DL 3 (D 60 mg/m2 + A 200 mg) and 4 (D 75 mg/m2 + A 200 mg) experienced dose-limiting toxicity, and both DLs were expanded. Overall, severe adverse events occurred more commonly on DL 4 than 3 (47% versus 18% of patients). PK data for docetaxel and ABT-751 were similar to reported literature. Best post-treatment prostate-specific antigen decline of ≥50% occurred in 60% and objective responses occurred in 45% of patients. Median overall survival was 24 months (95% confidence interval 8.3–37.7 months). Conclusions: The combination of ABT-751 and docetaxel is safe and active in CRPC. Based on the cumulative safety analysis, the recommended phase II dose of ABT-751 is 200 mg daily with docetaxel 60 mg/m2 for this patient population.

Efficacy of carboplatin-taxane combinations in the management of castration-resistant prostate cancer: a pooled analysis of seven prospective clinical trials

Background: Docetaxel is associated with prolonged survival in castration-resistant prostate cancer (CRPC). Platinum compounds have modest but distinct single-agent activity. Carboplatin may have greatest potential for benefit when combined with taxanes. We investigated whether there is a subset of patients with CRPC for whom the efficacy of combination taxane–estramustine–carboplatin (TEC) chemotherapy may be greatest. Patients and methods: Individual patient data (n = 310) were obtained from seven trials using TEC chemotherapy. Prostate-specific antigen (PSA) response was defined as ≥50% post-therapy decline from baseline. Overall survival was defined from baseline to death from any cause. Logistic and Cox regression were used to investigate heterogeneity in outcome to TEC by patient and disease characteristics. Predicted survival probabilities were calculated from the Halabi Cancer and Leukemia Group B (CALGB) nomogram. Results: The pooled PSA response proportion was 69% [95% confidence interval (CI) 56% to 80%]. There was no evidence of differential PSA response by disease characteristics. Established prognostic factors were associated with survival. The pooled 12-month survival estimate of 79% (95% CI 71% to 84%) was higher than the median 59% 12-month nomogram-predicted survival. Conclusions: TEC chemotherapy has significant clinical activity in CRPC. A randomized, controlled trial evaluating the addition of carboplatin to taxane-based chemotherapy is needed to elucidate the value of carboplatin in CRPC.

Sunitinib malate for metastatic castration-resistant prostate cancer following docetaxel-based chemotherapy

Background: Systemic therapy options are limited for metastatic castration-resistant prostate cancer (CRPC) patients who progress following docetaxel (Taxotere). This phase II trial evaluated sunitinib malate in patients with progressing metastatic CRPC following prior docetaxel. Patients and methods: Patients with metastatic CRPC progressing following one to two chemotherapy regimens including docetaxel were included. The primary end point was progression-free survival (PFS) per radiographic and clinical evaluations. Oral sunitinib was administered 50 mg/day 4-weeks on followed by 2-weeks off per cycle up to a maximum of eight cycles or until clinical progression or intolerable toxicity. Results: Thirty-six patients with a median age of 69.5 years were accrued. The median PFS was 19.4 weeks with a 12-week PFS of 75.8%. Four patients (12.1%) had a ≥50% prostate-specific antigen (PSA) decline and seven (21.2%) had a ≥30% PSA decline. Two of 18 patients (11.1%) with measurable disease demonstrated 30% declines by RECIST and eight (44.4%) displayed some shrinkage. A decline in pain score ≥2 points occurred in 13.6% of 22 assessable patients. Drug discontinuation due to toxic effects occurred in 52.8% of patients. Conclusion: Sunitinib malate demonstrated promising activity in metastatic CRPC progressing after prior docetaxel.

Incidence, presenting features and outcome of extramedullary disease in multiple myeloma: a longitudinal study on 1003 consecutive patients

Background: There are few data on the incidence and prognosis of extramedullary (EM) multiple myeloma (MM). There are concerns about a possible increase of EM relapses with the expanding use of high-dose therapy (HDT) and biological agents. Patients and methods: The incidence of EM disease, its relationship with prior exposure to HDT or novel agents, and its prognostic impact were analyzed in 1003 MM patients. Based on the different therapies available, three periods were considered: 1971–1993, conventional-dose chemotherapy; 1994–1999, HDT for younger patients; and 2000–2007, introduction of novel agents. Results: Overall, 13% of patients had EM disease, 7% at diagnosis and 6% later. In the 2000–2007 period, there was a significant increase of EM involvement, at diagnosis (P = 0.02) and during follow-up (P = 0.03). The risk of EM spread was not significantly increased after HDT [hazard ratio (HR 0.6)], bortezomib (HR 1.62), or thalidomide/lenalidomide (HR 1.07). EM disease was associated with shorter overall (HR 3.26, P < 0.0001) and progression-free (HR 1.46, P = 0.04) survival. Conclusions: The incidence of EM disease has increased, probably due to the availability of more sensitive imaging techniques and the prolongation of patients’ survival. HDT or novel agents seem not to increase the risk of EM disease. EM involvement confers a poor prognosis.

The frequency, manifestations, and duration of prolonged cytopenias after first-line fludarabine combination chemotherapy

Background: Fludarabine-based chemoimmunotherapy has well-recognised efficacy and short-term toxicity in the treatment of lymphoid malignancies. However, the presence and significance of prolonged cytopenias after completion of treatment have not been thoroughly quantified. Methods: Sixty-one patients receiving initial therapy with fludarabine-based regimens were categorised according to the presence of post-treatment cytopenias (haemoglobin <110–130 g/l depending on sex and age, neutrophils <2.0 x 109/l, or platelets <140 x 109/l) lasting >3 months. Results: Persistent cytopenias unrelated to persistent disease were found in 43% of patients. Cytopenias were associated with clinically important rates of infection and transfusion requirement (P = 0.03) and predicted for worse overall survival (61% versus 96% at 60 months, P = 0.05). Increasing age predicted for persistent cytopenias (P = 0.02), but the presence of pretreatment cytopenias and delivered dose intensity were not predictive. The median times to resolution of anaemia, neutropenia, and thrombocytopenia were 7, 9, and 10 months, respectively. Conclusions: Cytopenias often persist >3 months after first-line fludarabine combination therapy and can lead to important clinical sequelae. Although cytopenias generally resolve over time, treating physicians should be aware of these factors when considering fludarabine combination chemotherapy and when documenting treatment response status in chronic lymphocytic leukaemia.

Expected long-term survival of patients diagnosed with acute myeloblastic leukemia during 2006-2010

Background: Treatment of acute myeloblastic leukemia (AML) has evolved over the past several decades. Therefore, currently available estimates of long-term survival, which are based on survival for patients treated with potentially now obsolete protocols, may not pertain to patients currently diagnosed. Methods: Using data from the 1973–2005 database of the Surveillance, Epidemiology, and End Results Program, we empirically validated a novel model-based method to project 5- and 10-year relative survival of AML patients and we applied the method to project relative survival of AML patients in the United States diagnosed during 2006–2010. Results: Empirical evaluation indicated that the modeling approach provides more accurate estimates of currently diagnosed patients than standard methods of survival analysis, such as cohort analysis or period analysis, in the majority of cases. Projected figures for 2006–2010 show 5- and 10-year relative survival estimates of 21.4% and 18.7% for all ages combined, 62.2% and 57.4% for ages 25–34, and 60.6% and 58.1% for ages 35–44. These estimates are substantially higher than the most up-to-date estimates obtained by standard survival analysis. Conclusion: Patients diagnosed with AML during 2006–2010 at younger ages have much higher long-term survival expectations than indicated by previously available survival statistics.

Phase I dose-finding study of paclitaxel with panitumumab, carboplatin and intensity-modulated radiotherapy in patients with locally advanced squamous cell cancer of the head and neck

Background: Panitumumab has the potential to improve the therapeutic ratio of concurrent chemoradiotherapy for squamous cell carcinoma of the head and neck (SCCHN). Patients and methods: This phase I dose-finding study investigated escalating doses of paclitaxel (Taxol) given concurrently with panitumumab, carboplatin and intensity-modulated radiotherapy (IMRT) for stage III–IVB SCCHN. Untreated patients with oral cavity, oropharynx, larynx, hypopharynx or unknown primaries were eligible. Additional eligibility criteria included measurable disease, good performance status and no contraindication to therapy. Patients received weekly fixed doses of panitumumab and carboplatin plus escalating doses of paclitaxel with IMRT. Results: Nineteen patients were enrolled on to two dose levels (DLs): weekly paclitaxel 15 mg/m2 (n = 3) and 30 mg/m2 (n = 16). One dose-limiting toxicity occurred in DL 2, which was declared the maximum tolerated dose. All patients experienced mucositis, primarily grade 3 or more. Oral pain, xerostomia, dysphagia, weight loss, dermatitis, nausea and acneiform rash were frequent. All patients had partial response according to RECIST, whereas the overall complete clinical response rate was 95%. At median follow-up of 21 months, 18 of 19 patients (95%) remained disease free. Conclusions: Panitumumab, carboplatin, paclitaxel and IMRT are well tolerated and appear highly active in the treatment of SCCHN. Further study of this regimen in SCCHN is warranted.

Malignant peritoneal mesothelioma: a multicenter study on 81 cases

Background: Malignant peritoneal mesothelioma (MPM) is a rare disease characterized by a difficult diagnosis, different types of presentation, variable course and poor prognosis. Materials and methods: Eighty-one patients with MPM observed in 14 Italian oncology institutions from 1982 to 2007 have been examined with the aim of delineating the history of MPM. Results: Presentation symptoms were ascites, abdominal pain, asthenia, weight loss, anorexia, abdominal mass, fever, diarrhea and vomiting in various associations. Computed tomography scan and echotomography signs were ascites, abdominal mass and peritoneal thickening. Peritoneal fluid cytology (61 cases) was positive for mesothelioma in 31 and for malignancy, not mesothelioma, in 13. Laparoscopy was carried out in 40 cases and laparotomy in 36. Thrombocytosis was present in 59 cases. Associated tumors diagnosed during the lifetime were colorectal cancer in two cases and cheek carcinoma, thyroid carcinoma, tongue carcinoma, bladder carcinoma and testicular seminoma. Thirty patients were treated with surgery and 45 with chemotherapy. The median survival time from diagnosis is 13 months. Ascites, fever and vomiting were significative variables at presentation; only vomiting holds significance in a multivariate analysis. Conclusions: MPM is a disease with various types of presentation, frequently associated with thrombocytosis, sometimes with other tumors. Survival and diagnosis time can differ in various types of MPM. Prognosis is poor.

Health care-related predictors of husbands' preparedness for the death of a wife to cancer--a population-based follow-up

Background: If we can learn how to increase preparedness before the death of a loved one, we can possibly decrease the next-of-kin's long-term morbidity. Methods: In a population-based study, 691 of 907 (76%) men in Sweden who lost a wife to cancer 4–5 years earlier answered an anonymous questionnaire about their preparedness at the time of their wife's death as well as potential predictors for preparedness. Results: A final logistic regression model indicates following predictors for preparedness, among others: the length of the widower's intellectual awareness time before his wife's death [relative risk (RR) 4.1, confidence interval (CI) 2.7–6.1], the widower could take in the information that his wife's disease could not be cured (RR 3.5, CI 2.3–5.2), the couple had arranged their economical affairs (RR 1.5, CI 1.3–1.7), the wife had stayed at a palliative care unit during her last months of life (RR 1.2, CI 1.1–1.4) and health care personnel supported the husband to participate in his wife's care (RR 1.6, CI 1.3–2.1). Conclusions: We identified several care-related factors that may influence the preparedness of men before their wife's death to cancer. These factors can be considered in future intervention studies aiming at influencing preparedness before the death of a loved one.

European Society for Medical Oncology (ESMO) Program for the Integration of Oncology and Palliative Care: a 5-year review of the Designated Centers' incentive program

Background: In 1999, the National Representatives of European Society for Medical Oncology (ESMO) created a Palliative Care Working Group to improve the delivery of supportive and palliative care (S + PC) by oncologists, oncology departments and cancer centers. They have addressed this task through initiatives in policy, education, research and incentives. As an incentive program for oncology departments and centers, ESMO developed a program of Designated Centers (DCs) for programs meeting predetermined targets of service development and delivery of a high level of S + PC. Method: The history, accreditation criteria and implementation of the DC incentive program is described. Results: Since 2004, 75 centers have applied for designation and 48 have been accredited including 34 comprehensive cancer centers (CCCs) in general hospitals and seven freestanding CCCs. Perceived benefits accrued from the accreditation included the following: improved status and role identification of the center, positive impact on daily work, positive impact on business activity and positive impact on funding for projects. Conclusions: The accreditation of DCs has been a central to the ESMO initiative to improve the palliative care provided by oncologists and oncology centers. It is likely that many other oncology departments and cancer centers already meet the criteria and ESMO strongly encourages them to apply for accreditation.

A phase I open-label dose-escalation study of oral BIBF 1120 combined with standard paclitaxel and carboplatin in patients with advanced gynecological malignancies

Background: The purpose of the phase I dose-escalation study was to evaluate the maximum tolerated dose (MTD) of BIBF 1120, an oral triple angiokinase inhibitor of vascular endothelial growth factor, platelet derived growth factor and fibroblast growth factor receptors, combined with paclitaxel and carboplatin. Patients and methods: Patients with advanced gynecological malignancies received BIBF 1120 twice-daily (b.i.d.) continuously at 100, 150, 200 or 250 mg, combined with paclitaxel (175 mg/m2) and carboplatin (area under the curve 5 min·mg/ml) every 3 weeks. The MTD, safety, pharmacokinetics (PK) and clinical activity were evaluated. Results: Twenty-two patients were treated. Three experienced dose-limiting toxic effects in the first treatment cycle: 1 of 13 at 200 mg b.i.d. BIBF 1120 [diarrhea, common terminology criteria for adverse events (CTCAE) grade 3]; two of two at 250 mg b.i.d. BIBF 1120 (elevated alanine aminotransferase and aspartate aminotransferase, CTCAE grade 3/4). The MTD was defined as 200 mg b.i.d. Principal adverse events were gastrointestinal disorders. No clinically relevant drug–drug interaction was observed after 20 days treatment with 200 mg b.i.d. BIBF 1120 on the PK of paclitaxel or carboplatin and vice versa. Conclusions: The MTD of BIBF 1120 in a 20-day continuous dosing regimen with standard-dose paclitaxel and carboplatin was 200 mg b.i.d. This combination had an acceptable safety profile and no clinically relevant drug–drug interactions. Further evaluation of this combination is warranted in this indication.

Phase I and pharmacokinetic study of lexatumumab (HGS-ETR2) given every 2 weeks in patients with advanced solid tumors

Background: Lexatumumab (HGS-ETR2) is a fully human agonistic mAb to the tumor necrosis factor-related apoptosis-inducing ligand receptor 2 that activates the extrinsic apoptosis pathway and has potent preclinical antitumor activity. Materials and methods: This phase 1, dose escalation study assessed the safety, tolerability, pharmacokinetics (PKs) and immunogenicity of lexatumumab administered i.v. every 14 days in patients with advanced solid tumors. Results: Thirty-one patients received lexatumumab over five dose levels (0.1–10 mg/kg). Most (26 of 31) received four or more cycles of treatment. One patient at 10 mg/kg experienced a possibly related dose-limiting toxicity of grade 3 hyperamylasemia. Nine patients achieved stable disease. One patient with chemotherapy-refractive Hodgkin's disease experienced a mixed response. Lexatumumab PKs were linear up to 10 mg/kg. At the 10 mg/kg dose, the mean (±standard deviation) t1/2b was 13.67 ± 4.07 days, clearance was 4.95 ± 1.93 ml/day/kg, V1 was 45.55 ml/kg and Vss was 79.08 ml/kg, indicating that lexatumumab distributes outside the plasma compartment. No human antihuman antibodies were detected. Conclusions: Lexatumumab can be safely administered every 14 days at 10 mg/kg. The PK profile supports this schedule. Further evaluation of lexatumumab at this dose schedule is warranted, including combination trials with other agents.

Phase I pharmacokinetic study of a weekly liposomal paclitaxel formulation (Genexol(R)-PM) in patients with solid tumors

Background: The aim of this study was to determine the maximum tolerated dose (MTD) and the pharmacokinetic profile of Genexol-PM in Asian cancer patients. Materials and methods: Patients (N = 24) refractory to previous chemotherapy received Genexol-PM as an 1-h infusion on a weekly basis for 3 weeks followed by a resting week. The starting dose was 80 mg/m2 and the maximum administered dose was 200 mg/m2. Results: The majority of patients had lung, nasopharyngeal and breast cancers and in eleven patients (46%), taxane-based chemotherapy had previously failed. The MTD was defined at 180 mg/m2. The most common grade 3 non-hematologic adverse events in cycle 1 were fatigue (4%) and neuropathy (4%) occurring mainly at 200 mg/m2. Five (21%) patients had partial response, nine (38%) had stable disease and seven (29%) had disease progression. Five of 11 previously taxane-refractory patients showed clinical benefit to Genexol-PM. The pharmacokinetics of Genexol-PM displayed dose-proportionality, with both the maximum concentration (Cmax) and the area under the concentration-time curve from zero to infinity (AUC0–) increasing by approximately four- and threefold, respectively, as the dose of Genexol-PM was escalated from 80 to 200 mg/m2. The median total-body clearance of Genexol-PM for all patients was 43.9 l/h. Conclusion: The weekly regimen of Genexol-PM was well tolerated and responses were observed in patients with refractory tumors, including patients who had failed taxane-based chemotherapy previously.

Trends in cancer mortality in the elderly in Japan, 1970-2007

Objective: The primary objective of this study is to describe cancer mortality rates and trends among Japanese elderly aged 65–84 years for the period 1970–2007. Materials and methods: Age-standardized mortality rates were calculated by the direct method using age-specific mortality rates at 5-year age intervals and weights based on the age distribution of the standard world population. The joinpoint regression model was used to describe changes in trends. Results: For all cancers combined, the mortality rate at age 65–84 years during 2000–2007 was 1145.13 (per 100 000 population) for men and 461.93 (per 100 000) for women. Mortality rates have declined in the past 10 years in both sexes. These favorable trends were driven largely by decreases in mortality for three leading cancers in the elderly men [lung, stomach and colorectal cancer (CRC)] and for two of the three most common cancers in the elderly women (stomach and CRC), combined with a leveling off of death rate from lung cancer in women. Conclusion: The population-based data in the current study underscore the importance of cancer research and prevention for the older segment in Japan to reduce the additional cancer burden among the growing number of elderly persons.

Postoperative nomogram for survival of patients with retroperitoneal sarcoma treated with curative intent

Background: Current American Joint Committee on Cancer retroperitoneal sarcoma (RPS) staging is not representative of patients with RPS specifically and has limited discriminative power. Our objective was to develop a RPS disease-specific nomogram capable of stratifying patients based on probability of overall survival (OS) after resection. Patients and methods: In all, 1118 RPS patients were evaluated at our institution (1996–2006). Patients with resectable, nonmetastatic disease were selected (n = 343) and baseline, treatment and outcome variables were retrieved. A nomogram was created and its performance was evaluated by calculating its discrimination (concordance index) and calibration and by subsequent internal validation. Results: Median follow-up and OS were 50 and 59 months, respectively. Independent predictors of OS were included in the nomogram: age (≥65), tumor size (≥15 cm), type of presentation (primary versus recurrent), multifocality, completeness of resection and histology. The concordance index was 0.73 [95% confidence interval (CI) 0.71–0.75] and the calibration was excellent, with all observed outcomes within the 95% CI of each predicted survival probability. Conclusions: A RPS-specific postoperative nomogram was developed. It improves RPS staging by allowing a more dynamic and robust disease-specific risk stratification. This prognostic tool can help in patient counseling and for selection of high-risk patients that may benefit from adjuvant therapies or inclusion into clinical trials.

Post-imatinib surgery in advanced/metastatic GIST: is it worthwhile in all patients?

Background: Surgical indication for metastatic gastrointestinal stromal tumor (GIST) treated with imatinib is not yet established. Materials and methods: We analyzed 80 patients who underwent surgery for metastatic GIST after imatinib therapy from July 2002 to October 2007. Patients were divided into those with surgery at best clinical response (group A, n = 49) and those with surgery at focal progression (group B, n = 31). Primary end points were progression-free survival (PFS) and disease-specific survival (DSS). Results: Two-year postoperative PFS was 64.4% in group A and 9.7% in group B (P < 0.01). In group A, median PFS was not reached; in group B, it was 8 months. Median DSS from the time of imatinib onset was not reached in either group. Five-year DSS was 82.9% in group A and 67.6% in group B (P < 0.01). Multivariate analysis confirmed a significantly shorter PFS and DSS in group B. Surgical morbidity occurred in 13 patients (16.3%). Conclusions: Surgery for focal progressive lesions could be considered as part of the second-line/third-line armamentarium in selected cases. Surgery of residual disease upon best clinical response seems associated with survival benefit compared with historical controls in similar patient collectives treated with imatinib alone. However, evidence from prospective randomized trials is needed to make definite recommendations.

Vitiligo is an independent favourable prognostic factor in stage III and IV metastatic melanoma patients: results from a single-institution hospital-based observational cohort study

Background: The clinical features and the prognostic relevance of vitiligo lesions in melanoma patients are still controversial. This prospective observational study was designed to characterise the clinical features of melanoma-associated vitiligo, to analyse the association with other autoimmune manifestations and to ascertain whether the development of vitiligo lesions carries a prognostic relevance on the clinical course of melanoma. Materials and methods: A total of 2954 consecutive patients have been included; multivariate analyses of distant metastasis-free survival (DMFS) and overall survival (OS) were carried out to ascertain the independent prognostic role of vitiligo as a time-dependent covariate. Results: Vitiligo was demonstrated in 83 of 2954 melanoma patients (2.8%). A significantly higher percentage of autoimmune diseases was demonstrated in vitiligo patients (7 of 83) with respect to patients without vitiligo (80 of 2871) (P = 0.004). Multivariate analyses selected the time-dependent covariate vitiligo as the favourable independent prognostic variable associated to a longer DMFS in stage III and a higher OS in both stage III and stage IV. Conclusion: Melanoma-associated vitiligo should be considered as a distinct clinical entity, separate from vitiligo vulgaris, and identifies a subgroup of patients characterised by a high prevalence of immune-mediated diseases and by a favourable prognosis.

A prospective monitoring of fatal serious adverse events (SAEs) in a Dutch Colorectal Cancer Group (DCCG) phase III trial (CAIRO) in patients with advanced colorectal cancer

Background: Early and correct assessment of treatment-related mortality is highly important in clinical cancer trials. However, no data are available on the quality of safety monitoring. Patients and methods: An on-site review was carried out by the study coordinators of the individual charts of all patients participating in the Capecitabine-Irinotecan-Oxaliplatin (CAIRO) study who had died within 30 days of the last administration of study drugs when death was accompanied by any other event than disease progression. The relationship between treatment and death was categorized as unrelated, remote, possible, or probable and submitted to an independent data monitoring committee (IDMC). These results were then compared with the initial assessment of the local investigator. Results: Forty of 820 patients qualified for review. The relationship between cause of death and study drugs was changed in 26 patients (65%). A major protocol violation (MPV) was identified in 12 of 14 patients with a probable relationship between cause of death and study treatment. Conclusions: There was little agreement between the relation as assessed by the local investigator compared with the IDMC. A quality control improves the assessment of safety results and the observed MPVs underscore the importance of educating medical staff and patients.

A double-blind randomized phase II study on the efficacy of topical eye treatment in the prevention of docetaxel-induced dacryostenosis

Background: Dacryostenosis is a common side-effect of weekly docetaxel (Taxotere). We investigate the efficacy of eyedrops containing corticosteroids (CS) versus artificial tears (AT) in patients receiving weekly docetaxel in the prevention of dacryostenosis. Patients and methods: Twenty patients receiving weekly docetaxel were evaluated. Forty eyes were double-blind randomized: AT in one eye and CS in the other eye were administered, six times daily, throughout the docetaxel administration. Patients were assessed for tearing and stenosis at weeks 3, 6, 9 and 26. The primary end point was the incidence of dacryostenosis in each group at 9 weeks. Results: At 9 weeks, punctal or canalicular stenosis was observed in 9 of 20 (45%) of the CS eyes and 9 of 20 (45%) of the AT eyes. Dacryostenosis was mild in 37 of 40 eyes (93%) and severe in 3 of 40 eyes (8%), with equal distribution in the CS and AT group. Tearing was present in 9 of 20 (45%) of the CS eyes and 8 of 20 (40%) of the AT eyes, of which two eyes without stenosis in each group. Conclusions: The incidence of dacryostenosis in patients receiving weekly docetaxel was not different for the AT- and the CS-treated eyes. The dacryostenosis was predominantly mild, not leading to surgical interventions.

Taxanes for breast cancer during pregnancy: a systematic review

The role of an all-oral chemotherapy containing lomustine (CCNU) in advanced,fs progressive Hodgkin lymphoma: a patient-friendly palliative option which can result in long-term disease control

Second-line treatments of advanced non-small-cell lung cancer: new evidence for clinical practice

Concomitant medications in cancer patients: should we be more active in their management?

Identifying optimal adjuvant treatment for individual patients: young age is still an issue?

VEGFR TKI 'resistance' or transient clinical insensitivity to VEGFR TKI in metastatic renal cell carcinoma

Irinotecan and mismatch repair deficiency

Potential role of everolimus in inducing cholestasis