Metronomic oral vinorelbine for the treatment of advanced non-small cell lung cancer: a multicenter international retrospective analysis.

PURPOSE: Metronomic oral vinorelbine (MOV) could be a treatment option for unfit patients with advanced non-small cell lung cancer (NSCLC) based on its safety profile and high patient compliance. METHODS: We retrospectively collected data on 270 patients [median age 76 (range 48-92) years, M/F 204/66, PS 0 (27)/1 (110)/≥ 2 (133), median of 3 serious comorbidities] with stage IIIB-IV NSCLC treated with MOV as first (T1) (67%), second (T2) (19%) or subsequent (T3) (14%) line. Schedules consisted of vinorelbine 50 mg (138), 40 mg (68) or 30 mg (64) three times a week continuously. RESULTS: Patients received an overall median of 6 (range 1-25) cycles with a total of 1253 cycles delivered. The overall response rate was 17.8% with 46 partial and 2 complete responses and 119 patients (44.1%) experienced stable disease > 12 weeks with an overall disease control rate of 61.9%. Median overall time to progression was 5 (range 1-21) months [T1 7 (1-21), T2 5.5 (1-19) and T3 4 (1-19) months] and median overall survival 9 (range 1-36) months [T1 10 (1-31), T2 8 (1-36) and T3 6.5 (2-29) months]. Treatment was extremely well tolerated with 2% (25/1253) G3/4 toxicity (mainly G3 fatigue and anemia) and no toxic deaths. We observed the longer OS 14 (range 7-36) months in a subset of squamous NSCLC patients receiving immunotherapy after metronomic oral vinorelbine. CONCLUSION: We confirmed MOV as an extremely safe treatment in a large real world population of advanced NSCLC with an interesting activity mainly consisting of long-term disease stabilization. We speculate the possibility of a synergistic effect with subsequent immunotherapy.

Metformin plus chemotherapy versus chemotherapy alone in the first-line treatment of HER2-negative metastatic breast cancer. The MYME randomized, phase 2 clinical trial.

PURPOSE: To investigate the efficacy of metformin (M) plus chemotherapy versus chemotherapy alone in metastatic breast cancer (MBC). METHODS: Non-diabetic women with HER2-negative MBC were randomized to receive non-pegylated liposomal doxorubicin (NPLD) 60 mg/m2 + cyclophosphamide (C) 600 mg/m2 × 8 cycles Q21 days plus M 2000 mg/day (arm A) versus NPLD/C (arm B). The primary endpoint was progression-free survival (PFS). RESULTS: One-hundred-twenty-two patients were evaluable for PFS. At a median follow-up of 39.6 months (interquartile range [IQR] 24.6-50.7 months), 112 PFS events and 71 deaths have been registered. Median PFS was 9.4 months (95% CI 7.8-10.4) in arm A and 9.9 (95% CI 7.4-11.5) in arm B (P = 0.651). In patients with HOMA index < 2.5, median PFS was 10.4 months (95% CI 9.6-11.7) versus 8.5 (95% CI 5.8-9.7) in those with HOMA index ≥ 2.5 (P = 0.034). Grade 3/4 neutropenia was the most common toxicity, occurring in 54.4% of arm A patients and 72.3% of the arm B group (P = 0.019). M induced diarrhea (G2) was observed in 8.8% of patients in Arm A. The effect of M was similar in patients with HOMA index < 2.5 and ≥ 2.5, for PFS and OS. CONCLUSIONS: The MYME trial failed to provide evidence in support of an anticancer activity of M in combination with first line CT in MBC. A significantly shorter PFS was observed in insulin-resistant patients (HOMA ≥ 2.5). Noteworthy, M had a significant effect on CT induced severe neutropenia. Further development of M in combination with CT in the setting of MBC is not warranted.

Human and porcine neurocysticercosis: differences in the distribution and developmental stages of cysticerci.

OBJECTIVE: To describe and compare the clinical impacts of neurocysticercosis (NC) caused by Taenia solium in humans and pigs. METHODS: Comparative study of the brains of 16 asymptomatic pigs and 35 human NC cases (15 asymptomatic and 20 symptomatic). RESULTS: In humans, cysticerci were more frequently located in the ventricles and subarachnoid space at the base of the brain (11.8%vs. 1.6%; P = 0.001 and 25.9%vs. 0%; P < 0.0001, respectively) while in pigs, cysticerci were more frequently found in the parenchyma (44.4%vs. 7.6%; P < 0.0001). In human brains, 75.9% of the cysticerci were calcified, while in pigs all cysticerci were in the vesicular stage. CONCLUSION: The duration of infection and the host-parasite relationship (such as immune reactivity and brain haemodynamics) differ between humans and pigs. This may account for the different distribution and stage of the cysticerci among humans and pigs.

Human neurocysticercosis: rightward hemisphere asymmetry in the cerebral distribution of a single cysticercus.

The distribution of single cysticerci between cerebral hemispheres was studied in 227 adult cases of calcified and vesicular neurocysticercosis (NC). A rightward lateralization of calcified cysticerci was significant only in women, whereas vesicular cysticerci were equally distributed in both hemispheres. Factors related with the differences in the inflammatory response and in the regional cerebral blood flow between genders could be involved.

A novel synthetic adjuvant effectively enhances the immunogenicity of the influenza vaccine.

Influenza vaccination is a key intervention to reduce morbidity and mortality provoked by this disease. To date, the challenge of improving its efficacy remains unmet. The immunogenic synthetic peptide GK1 from Taenia crassiceps cysticerci was tested herein in its capacity as adjuvant, co-administered with the inactivated anti-influenza vaccine before and after challenge with influenza virus in both young and aged mice. Co-administration of GK1 with the influenza vaccine increased levels of anti-influenza antibodies in aged mice before and after infection, reduced the local inflammation that accompanied influenza vaccination itself and favored virus clearance after infection in both young and aged mice.

Prevalence and management of pain in Italian patients with advanced non-small-cell lung cancer.

Pain is a highly distressing symptom for patients with advanced cancer. WHO analgesic ladder is widely accepted as a guideline for its treatment. Our aim was to describe pain prevalence among patients diagnosed with advanced non-small-cell lung cancer (NSCLC), impact of pain on quality of life (QoL) and adequacy of pain management. Data of 1021 Italian patients enrolled in three randomised trials of chemotherapy for NSCLC were pooled. QoL was assessed by EORTC QLQ-C30 and LC-13. Analgesic consumption during the 3 weeks following QoL assessment was recorded. Adequacy of pain management was evaluated by the Pain Management Index (PMI). Some pain was reported by 74% of patients (42% mild, 24% moderate and 7% severe); 50% stated pain was affecting daily activities (30% a little, 16% quite a bit, 3% very much). Bone metastases strongly affected presence of pain. Mean global QoL linearly decreased from 64.9 to 36.4 from patients without pain to those with severe pain (P<0.001). According to PMI, 616 out of 752 patients reporting pain (82%) received inadequate analgesic treatment. Bone metastases were associated with improved adequacy and worst pain with reduced adequacy at multivariate analysis. In conclusion, pain is common in patients with advanced NSCLC, significantly affects QoL, and is frequently undertreated. We recommend that: (i). pain self-assessment should be part of oncological clinical practice; (ii). pain control should be a primary goal in clinical practice and in clinical trials; (iii). physicians should receive more training in pain management; (iv). analgesic treatment deserves greater attention in protocols of anticancer treatment.

Supportive care in patients with advanced non-small-cell lung cancer.

The present study describes supportive care (SC) in patients with advanced non-small-cell lung cancer (NSCLC), evaluating whether it is affected by concomitant chemotherapy, patient's performance status (PS) and age. Data of patients enrolled in three randomised trials of first-line chemotherapy, conducted between 1996 and 2001, were pooled. The analysis was limited to the first three cycles of treatment. Supportive care data were available for 1185 out of 1312 (90%) enrolled patients. Gastrointestinal drugs (45.7%), corticosteroids (33.4%) and analgesics (23.8%) were the most frequently observed categories. The mean number of drugs per patient was 2.43; 538 patients (45.4%) assumed three or more supportive drugs. Vinorelbine does not produce substantial variations in the SC pattern, while cisplatin-based treatment requires an overall higher number of supportive drugs, with higher use of antiemetics (41 vs 27%) and antianaemics (10 vs 4%). Patients with worse PS are more exposed to corticosteroids (42 vs 30%). Elderly patients require drugs against concomitant diseases significantly more than adults (20 vs 7%) and are less frequently exposed to antiemetics (12 vs 27%). In conclusion, polypharmacotherapy is a relevant issue in patients with advanced NSCLC. Chemotherapy does not remarkably affect the pattern of SC, except for some drugs against side effects. Elderly patients assume more drugs for concomitant diseases and receive less antiemetics than adults.

Hypnosis in the treatment of anticipatory nausea and vomiting in patients receiving cancer chemotherapy.

AIMS AND BACKGROUND: In addition to nausea and vomiting following chemotherapy treatment, cancer patients can experience these side effects prior to a treatment session, the so-called anticipatory nausea and vomiting. As various psychological and neurophysiological aspects have been claimed to be implied in its etiopathogenesis, the present paper aims to shortly review the etiological, epidemiological and therapeutical assumptions on the topic, in particular the psychological-behavioral therapies. PATIENTS AND METHODS: The present study was carried out on 16 consecutive adult cancer patients affected by chemotherapy-induced anticipatory nausea and vomiting who had received at least four treatment cycles. All of them were submitted to induction of relaxation followed by hypnosis. RESULTS: In all subjects anticipatory nausea and vomiting disappeared, and major responses to chemotherapy-induced emesis control were recorded in almost all patients. CONCLUSIONS: The experience highlights the potential value of hypnosis in the management of anticipatory nausea and vomiting; furthermore, the susceptibility to anticipatory nausea and vomiting is discussed under the psychoanalytic point of view.

The impact of a psychological intervention on quality of life in non-metastatic breast cancer.

The aim of this study was to determine whether psychological intervention had a beneficial effect on the quality of life and behaviour of women diagnosed with breast cancer. 36 consecutive patients with non-metastatic breast cancer assigned to surgery and systemic chemotherapy were randomised to receive either psychological intervention (weekly cognitive individual psychotherapy and bimonthly family counselling) or standard follow-up. Personality (16-PF and IIQ), quality of life (FLIC), and depression (BDI) scores were the endpoints for this study, and the questionnaires were completed by the patients at diagnosis, and up to 9 months after diagnosis. Cognitive psychotherapy and family counselling improved both depression and quality of life indexes compared with the control group. Better emotional coping behaviours were also revealed by some changes in personality traits in the intervention group.

Safety of first trimester exposure to histamine H2 blockers. A prospective cohort study.

The objective of this study was to examine whether H2 blockers represent a major teratogenic risk. This prospective cohort study was done at the Motherisk Program, a Teratology Information Service, Toronto, Canada. The subjects included 178 women who contacted Motherisk about gestational H2-blocker use, and 178 controls matched for maternal age, smoking, and heavy alcohol consumption. The main outcome measures were primary--major malformations, and secondary--pregnancy outcome, method of delivery, gestational age, prematurity, birthweight, small for gestational age infants, neonatal health problems, and developmental milestones. No increase in major malformations was found following first trimester exposure to H2 blockers [2.1% vs 3.5% (controls), mean difference (95% CI) -1.4% (-5.2, +2.4)]. No other aspects of pregnancy outcome or neonatal health differed between groups. This study suggests that H2-blocker exposure during the first trimester does not represent a major teratogenic risk.

Glial fibrillary acidic protein (GFAP) immunochemical profile after junin virus infection of rat cultured astrocytes.

Cultured astrocytes derived from newborn rat brain were inoculated with Junin virus (JV) to characterize their response to infection by means of their glial fibrillary acidic protein (GFAP) immunochemical profile. Samples from 1 to 11 days post-inoculation (pi), as well as matched controls, were serially harvested for GFAP labeling by peroxidase-antiperoxidase (PAP) method. It was only at day 3 that significantly greater values of GFAP staining (P < 0.05) were disclosed by three complementary approaches: image analysis, ELISA and immunoblot densitometry. Since such increase was abolished by Triton X-100 treatment, soluble GFAP fraction appeared responsible for the early though transient enhancement of GFAP immunoreactivity that followed viral inoculation.

Evaluación de pruebas alternativas al hemocultivo en el diagnóstico de la sepsis neonatal precoz / Evaluation of alternative hemoculture tests for the diagnosis of early neonatal tests

Se realizó un estudio prospectivo en 90 neonatos provenientes de madres con rotura prematura de membrana (RPM) mayor de 24h, con el objeto de establecer la incidencia de sepsis neonatal precoz (SNP), determinar su etiología y evaluar la capacidad diagnóstica de pruebas alternativas al hemocultivo; cultivo de hisopado de conducto auditivo externo, de aspirado nasofarígeo y de aspirado gástrico. En los neonatos nacidos vivos, se rigistró una incidencia del 4 por ciento (n=90) de RPM mayor de 24 h, y 6,9//(16/2293 recién nacidos vivos) padecieron SNP. La incidencia de SNP en neonatos de madres con RPM mayor de 24 h fue del 17,8 por ciento (16/90) y se distribuyó de la siguiente forma: 3,3 por ciento (3/90) asociado exclusivamente a RPM sin otro factor agravante, 5,6 por ciento (5/90) cuando se asoció la RPM a corioamnionitis y 8,9 por ciento (8/90) con prematurez. Con respecto a los agentes etiológicos de SNP, predominaron los Gram positivos y, dentro de ellos, Staphylococcus aureus. Ninguna de las pruebas evaluadas alcanzó la seguridad diagnóstica (sensibilidad más especificidad) necesaria para ser utilizada como pruebas alternativas al hemocultivo para diagnóstico de SNP por RPM mayor de 24 h. No obstante, ellas pueden ser empleadas como pruebas complementarias para contribuir a la identificación de recién nacidos de alto riesgo que hayan estado expuestos a infección del líquido amniótico o corioamnionitis

The combination of mitomycin, vinblastine and cisplatin is active in the palliation of stage IIIB-IV non-small-cell lung cancer.

Twenty-eight patients with stage IIIB-IV non-small-cell lung cancer were treated with mitomycin C, vinblastine and cisplatin (MVP) in a phase II--minimax 2-stage design--randomized trial (with cisplatin plus etoposide as control arm). As indicated by the study design, the accrual was stopped after the 11th responder, and the combination was considered as active at the 40% level. Forty-six percent of patients had an improvement of their initial Karnofsky performance score, lasting a median of 24 weeks, and about 38% had a complete relief of symptoms. Hematologic toxicity was moderate to severe in about 50% of patients, and neurologic toxicity in about 18%; no grade 4 toxicity was observed. The estimated median progression-free survival was of 25 weeks. The observed activity and manageability, together with the positive effect on patient quality of life, account for a positive evaluation of MVP as a palliative treatment in advanced non-small-cell lung cancer.