Rates of major complications during neoadjuvant and adjuvant chemotherapy for early breast cancer: An off study population.

OBJECTIVES: To determine the incidence and risk factors for thromboembolic events (TE) and febrile neutropenia (FN) in patients receiving systemic chemotherapy for early breast cancer (EBC). METHODS: 325 patients received FEC75, FEC100-T or ECaP for EBC in 2013. RESULTS: TE occurred in 7.4% and FN in 19.1% of patients. Risk factors for TE were: central venous catheter (p = 0.011). Risk factors for FN were: FEC100-T treatment versus FEC75 and ECaP (p ≤ 0.001); lower pre-treatment neutrophil count (p = 0.009) and poorer performance status (p = 0.012). Two patients died from treatment-related toxicities. CONCLUSION: In real-world experience, the majority of patients completed adequate treatment, despite significant complications.

Febrile Neutropenia Rates According to Body Mass Index and Dose Capping in Women Receiving Chemotherapy for Early Breast Cancer.

AIMS: Studies suggest worse outcomes in obese women with breast cancer than in non-obese women. One potential reason may be that oncologists 'dose cap' adjuvant chemotherapy in obese patients in order to avoid excessive toxicity. Reductions from standard dosing may compromise survival outcomes in the curative setting. Here we describe the body mass index (BMI) distribution of patients in a non-trial population, the frequency with which oncologists dose cap and its effect on febrile neutropenia chemotherapy toxicity. MATERIALS AND METHODS: In this non-randomised study, electronic patient records retrospectively identified patients with early breast cancer who initiated neoadjuvant or adjuvant chemotherapy at the Royal Marsden Hospital between 1 January and 31 December 2013. Baseline data included age, BMI, performance status, tumour characteristics, granulocyte colony-stimulating factor and comorbidities. Chemotherapy doses, rates of dose capping across BMI groups and rates of febrile neutropenia were reported. RESULTS: In total, 325 patients were eligible: 79 (24.5%) were obese (BMI ≥ 30), 109 (33.5%) were overweight (BMI ≥25 - <30) and 137 (42%) were normal bodyweight (BMI < 25). Sixteen patients (20.5%) in the obese group received dose-capped chemotherapy. Overall, 62 patients (19%) had an episode of febrile neutropenia. Obese patients receiving uncapped chemotherapy did not experience a significant difference in febrile neutropenia rates when compared with overweight or normal bodyweight groups (P = 0.5798). The febrile neutropenia rate in obese patients receiving capped chemotherapy was 6.5%, compared with 24% in obese patients receiving uncapped chemotherapy (P = 0.1216). CONCLUSION: In a non-trial population of obese patients, dose capping is frequently used. Obese patients receiving uncapped chemotherapy do not experience increased febrile neutropenia rates when compared with uncapped overweight or normal bodyweight patients. Furthermore, dose capping was associated with a trend towards lower rates of febrile neutropenia than in other groups and may indicate relative under-dosing of chemotherapy. This supports international guidelines that state that obese patients should not be dose capped.

Disclosure of cancer diagnosis: the Greek experience.

PURPOSE: To analyze the attitude of Greek health professionals towards truth disclosure and factors that may influence it. METHODS: Through a self-completed questionnaire, we studied the attitudes over the initial disclosure of cancer diagnosis to cancer patients of 132 doctors and 123 nurses, partly involved in cancer patients' care, in 5 general hospitals of Crete, Greece. RESULTS: Eighty-nine percent of the participants considered information as patient's right and 88% as professional's ethical duty, 64% believed that the whole truth should be revealed, 90% avoided the word "cancer" in the communication and 39% disclosed cancer diagnosis at patient's direct asking. Respondents informed 1/10 of their new cancer patients, mainly due to perceived limited responsibility (23%), patient's low cognitive state (22%), fear of harming the patient (17%) and relatives' objection (15%). Sixteen percent of fellows acknowledged to themselves the responsibility to inform patients. Cooperation, compliance and arrangement of patient's personal issues were considered as benefits from accurate disclosure (88%, 83% and 75%, respectively), the latter more among doctors than nurses (p=0.01) and medical than surgical professionals (p=0.03). Thirty-six percent of the respondents considered the presence of a psychologist necessary during disclosure, nurses more than doctors (p<0.001). CONCLUSION: Despite adequate theoretical background, Greek non-cancer specialists, doctors and nurses, initially inform accurately a small part of their cancer patients. Appropriate training programs for doctors and non-medical health professionals involved in cancer patients' management are required to upgrade professional-patient communication.

A phase I clinical trial of weekly oral topotecan for relapsed small cell lung cancer.

PURPOSE: To determine the dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD) of oral topotecan administered weekly in patients with relapsed small cell lung cancer (SCLC). PATIENTS AND METHODS: Patients were treated with oral topotecan on days 1, 8, and 15, every 28 days. The dose was escalated by 0.5 mg/m² increments from the starting dose of 3 mg/m² until the MTD was reached. DLTs were defined as grade 4 neutropenia, febrile neutropenia, grade 4 thrombocytopenia, non-hematologic toxicity ≥grade 3, any toxicity precluding the treatment on days 8 or 15 of the first cycle, or delay of the second cycle for more than 7 days. RESULTS: Eighteen patients were enrolled. Thirteen patients received oral topotecan as second-line and five as third- or further-line treatment. The DLT level was reached at 4.5 mg/m², and the MTD was determined to be 4 mg/m². DLTs consisted of grade 2/3 neutropenia and grade 2 thrombocytopenia precluding treatment on day 15 of the first cycle or on day 1 of the second cycle. The most frequent toxicities were grade 2-3 neutropenia (27.8 % of patients), grade 2-3 anemia (33.3 %), grade 2 thrombocytopenia (16.7 %), and grade 2-3 fatigue (44.4 %). The response rate was 11.1 %, the median progression-free survival 2.3 months, and the median overall survival 5.1 months. CONCLUSION: The recommended phase II dose of weekly oral topotecan in pretreated patients with SCLC is 4 mg/m² on days 1, 8, and 15 every 28 days.

Paclitaxel in combination with carboplatin as salvage treatment in patients with castration-resistant prostate cancer: a Hellenic oncology research group multicenter phase II study.

INTRODUCTION: To evaluate the efficacy and tolerance of biweekly paclitaxel and carboplatin combination in patients with castration-resistant prostate cancer. PATIENTS AND METHODS: Patients were treated with paclitaxel at the dose of 135 mg/m(2) followed by carboplatin AUC 3 on day 1 every 2 weeks in cycles of 28 days. RESULTS: Thirty-eight patients with castration-resistant prostate cancer were enrolled, and all of them had received frontline chemotherapy with docetaxel and prednisone, while 24 (63.2 %) had received 2 or more prior chemotherapy regimens. In an intention-to-treatment analysis, a clinical and/or biochemical response (>50 % decline) was observed in 10 patients (26.3 %; 95 % CI, 12.3-40.3 %), stable disease in 13 (34.2 %) and progressive disease in 15 (39.5 %). The median duration of response was 6.1 months (range, 1.0-9.8), the median time to tumor progression (TTP) 3.6 months (95 % CI, 2.1-5.2) and the median overall survival 9.9 months (95 % CI, 6.2-13.6). The probability for 1-year survival was 43 %. Grade 3 and 4 neutropenia was observed in three (7.9 %) and nine (23.7 %) patients, respectively. CONCLUSION: The biweekly administration of paclitaxel/carboplatin regimen in patients with castration-resistant prostate cancer is an active and well-tolerated regimen which merits to be further evaluated in the context of salvage treatment.

A multicenter phase II trial of docetaxel and capecitabine as salvage treatment in anthracycline- and taxane-pretreated patients with metastatic breast cancer.

OBJECTIVE: To evaluate the efficacy and safety of docetaxel plus capecitabine (DC) combination as salvage treatment in anthracycline- and taxane-pretreated patients with metastatic breast cancer (MBC). PATIENTS AND TREATMENT: Patients with MBC who had disease progression after initial chemotherapy with anthracyclines (n = 29; 100 %) and taxanes (n = 11; 37.9 %) were treated with oral capecitabine 950 mg/m(2) twice daily on days 1-14 and docetaxel 75 mg/m(2) on day 1 every 3 weeks. Nineteen (65.5 %) patients received this regimen as second line and 10 (34.5 %) as ≥3rd line of therapy. All patients were evaluable for response and toxicity. RESULTS: Complete response occurred in two (6.9 %) patients and partial response in eleven (37.9 %) for an overall response rate of 44.8 % (95 % CI 26.7-62.9 %). Eleven women (37.9 %) had stable disease and five (17.2 %) progressive disease. Of the eleven patients previously treated with anthracyclines and taxanes, five (45.5 %) responded to DC combination. The median duration of response was 5.7 months (range 3.4-64.2), the median time to disease progression 9.3 months (range 1.2-58), and the median overall survival 25.5 months. No toxic death occurred. Neutropenia grade 4 occurred in 58.6 % of patients and three of them (10.3 %) developed neutropenic fever. Non-hematological toxicities were manageable with grade 3 hand-foot syndrome occurring in 6.9 % of the patients, fatigue in 3.4 %, and neurotoxicity in 3.4 %. CONCLUSION: The DC combination is a valuable regimen as salvage treatment in anthracycline- or anthracycline and taxane-pretreated patients with MBC.

Glomerular expression of toll-like receptor-9 in lupus nephritis but not in normal kidneys: implications for the amplification of the inflammatory response.

Toll-like receptors recognising self-derived nucleic acids may participate in the pathogenesis of autoimmune diseases. Following the description of an enhanced population of toll-like receptor-9 (TLR-9) expressing auto-antibody producing B lymphocytes in active lupus, we explored the expression of TLR-9 in the renal tissue of patients with lupus. TLR-9 expression was studied in the kidneys of 12 lupus and 10 control samples from macroscopically unaffected areas of patients with renal adenocarcinoma by immunohistochemistry. A semiquantitative score was assigned separately for tubular, interstitial and glomerular expression. TLR-9 was expressed in the renal tubules and interstitial tissue in both patients with lupus and controls. Six of 12 patients with lupus with proliferative or membranous nephritis - as compared to none of the controls - exhibited both tubulointerstitial and glomerular TLR-9 expression. Biopsies with glomerular TLR-9 expression had a higher activity index (mean +/- SD, 6.3 +/- 3.5 in the presence of TLR-9 glomerular expression as compared to 1.3 +/- 1.8 in its absence, P = 0.015, t-test). This study documents for the first time the up-regulation of TLR-9 within the glomerulus of patients with lupus nephritis. Activation of TLR-9 expressing glomerular cells by endogenous nucleic acids (nucleosomes) may amplify the inflammatory response.

Platelets and white blood cell subpopulations among patients with myocardial infarction and unstable angina.

Platelet (PLT)-endothelial cell and PLT-leukocyte interactions at lesion-prone sites might trigger a local inflammatory response early in the genesis of atherosclerosis and contribute to plaque destabilization leading to acute coronary syndromes (ACS). The aim of this study was to assess the PLT count, mean PLT volume (MPV), PLT mass, white blood cell (WBC; including eosinophils) and plasma interleukin (IL)-5, in patients with ACS and controls. PLT count, MPV, PLT mass, WBC and eosinophil percentage were determined in 167 consecutive patients with ACS (86 with acute myocardial infarction, AMI, and 81 unstable angina, UA) and 83 controls. Plasma IL-5 was measured in some patients and controls. Patients were considered in subgroups depending on smoking status and if they had or did not have diabetes mellitus (DM). The PLT count was lower in the UA and AMI groups although this did not always achieve significance. The MPV was significantly raised in all patient groups except in DM non-smokers with UA or AMI. All AMI patients had significantly higher WBC counts compared with controls. The percentage of eosinophils was lower in the UA and AMI groups although this did not always achieve significance. Plasma IL-5 levels were significantly increased in the UA and AMI groups. In conclusion, patients with ACS present with changes in the count of several cell types. These cells may become therapeutic targets and these changes may also act as markers of myocardial damage or prognosis.

A dose escalation study of biweekly oral vinorelbine and gemcitabine in patients with solid tumors.

PURPOSE: To determine the maximum tolerated doses (MTDs) and the dose-limiting toxicities of a biweekly administration of oral vinorelbine and gemcitabine in patients with advanced solid tumors. PATIENTS AND METHODS: Twenty-eight patients with advanced stage solid tumors were enrolled, and 12 (42.9%) of them were chemotherapy naive. Escalating doses of vinorelbine (50-70 mg/m2 per os) and gemcitabine (800-1,000 mg/m2 as a 30-min intravenous infusion) were administered on days 1 and 15 in 4-week cycles. RESULTS: MTDs were reached at 70 mg/m2 p.o. for vinorelbine and 900 mg/m2 for gemcitabine. Grade 4 neutropenia, febrile neutropenia, grade 4 nausea/vomiting and treatment delay due to grade 3 neutropenia were the dose-limiting events during the first cycle of chemotherapy. A total of 94 chemotherapy cycles were administered with only one episode of febrile neutropenia and no toxic deaths. Severe (grade 3-4) neutropenia occurred in 10% of cycles while non-hematological toxicity was mild with grade 2-3 asthenia occurring in 17 (18%) cycles. Objective responses were achieved in patients with prostate and non-small cell lung cancer. CONCLUSIONS: The combination of biweekly oral vinorelbine (70 mg/m2) and gemcitabine (900 mg/m2) is a well-tolerated regimen with promising results in patients with advanced solid tumors.

Ear-nose-throat manifestations of autoimmune rheumatic diseases.

Ear-nose-throat (ENT) manifestations of connective tissue disorders represent a diagnostic challenge for clinicians as they often constitute the initial sign of an otherwise asymptomatic autoimmune disease. Moreover, in patients with known autoimmune rheumatic diseases, ENT manifestations can be overlooked. Hearing disturbances may be seen in patients with systemic lupus erythematosus, Wegener's granulomatosis, relapsing polychondritis, polyarteritis nodosa, Cogan's syndrome, Sjögren's syndrome, and less frequently in Churg-Strauss syndrome and Adamantiades-Behçet's disease. Nose and paranasal sinuses are variably affected during the course of Wegener's granulomatosis, Churg-Strauss syndrome, relapsing polychondritis and sarcoidosis. Recurrent mucosal ulcerations are common in systemic lupus erythematosus and Adamantiades-Behçet's disease. Xerostomia is a common feature of primary and secondary Sjögren's syndrome; salivary gland enlargement may be also seen in these patients, as well as in patients with sarcoidosis. The cricoarytenoid joint can be involved during the course of rheumatoid arthritis, ankylosing spondylitis and gout; osteoarthritic changes have also been described. Motility disorders of the upper and/or the lower portions of the esophagus have been reported in patients with dermatomyositis/polymyositis, systemic sclerosis and systemic lupus erythematosus. Trigeminal nerve dysfunction may occur in patients with Sjögren's syndrome, systemic sclerosis, systemic lupus erythematosus and mixed connective tissue disease. Peripheral facial nerve palsy has been described to complicate the course of Sjögren's syndrome and sarcoidosis.

Gastric carcinoid in a young woman with systemic lupus erythematosus and atrophic autoimmune gastritis.

BACKGROUND: Gastric carcinoid is a rare tumour that is associated with chronic atrophic gastritis in the majority of cases. It usually occurs in the 6th or 7th decade of life and is rarely diagnosed in patients under 30 years of age. METHODS: We describe a case of multiple gastric carcinoids in a 23-year-old woman with systemic lupus erythematosus and atrophic autoimmune gastritis--an association that has not been reported previously. RESULTS: The combination of atrophic autoimmune gastritis and gastric carcinoid with other autoimmune disorders has rarely been reported in the English medical literature. CONCLUSION: The fact that it mostly concerns (relatively) young patients may suggest a potential causative relation between those autoimmune disorders and the early development of atrophic gastritis with hypergastrinaemia, which subsequently leads to the occurrence of gastric carcinoid tumours at a young age.

Gastric Carcinoid in a Young Woman with Systemic Lupus Erythematosus and Atrophic Autoimmune Gastritis.

BACKGROUND: Gastric carcinoid is a rare tumour that is associated with chronic atrophic gastritis in the majority of cases. It usually occurs in the 6th or 7th decade of life and is rarely diagnosed in patients under 30 years of age. METHODS: We describe a case of multiple gastric carcinoids in a 23-year-old woman with systemic lupus erythematosus and atrophic autoimmune gastritis--an association that has not been reported previously. RESULTS: The combination of atrophic autoimmune gastritis and gastric carcinoid with other autoimmune disorders has rarely been reported in the English medical literature. CONCLUSION: The fact that it mostly concerns (relatively) young patients may suggest a potential causative relation between those autoimmune disorders and the early development of atrophic gastritis with hypergastrinaemia, which subsequently leads to the occurrence of gastric carcinoid tumours at a young age.