Vinorelbine-based chemotherapy in hormone refractory prostate cancer

Background: No consensus exists regarding further therapy for the management of hormone-refractory prostate cancer. In this phase II study, the combination of Vinorelbine with 5-Fluorouracil and folinic acid (FLN regimen) was evaluated in patients with progressive or resistant disease after hormone therapy. Patients and Methods: Thirty-four patients were treated with Vinorelbine at a dose of 20 mg/m 2 intravenously (i.v.) on days 1 and 3, folinic acid (FA), 100 mg/m 2 i.v. and 5-Fluorouracil (5-FU), 350 mg/m 2 i.v. as a short infusion on days 1 to 3. The therapy was given in an out-patient setting, every 3 weeks. Results: All of the 34 eligible patients were evaluable for toxicity and 30 for activity. A total of 127 cycles was administered (91% at full dose). Among the 15 patients with measurable disease, four had a partial response (26.6%; C.I. 95%, 28.3% to 65.7%) and four achieved stable disease. In 14 patients (47%) a clinical benefit was documented. Six out of 15 patients with bone-only involvement had stable disease (40%). The median duration of stabilization and partial response was 16 weeks (range 4-24 weeks). The most common toxicity was hematological: Grade 4 (NCI-CTC scale) in five patients at re-cycle. Other toxicities were of low incidence and easy to manage. Conclusion: The encouraging results obtained with the FLN regimen in terms of clinical benefit and its predictable and manageable toxicity support the palliative role of this chemotherapeutic strategy in hormone-refractory prostate patients

Phase I and pharmacologic study of weekly gemcitabine and paclitaxel in chemo-naïve patients with advanced non-small-cell lung cancer

Background. Gemcitabine (GEM) and paclitaxel (TAX) are active, non-cross-resistant drugs in non-small-cell lung cancer (NSCLC). We performed a phase I study to determine the maximum-tolerated dose (MTD), antitumor activity and pharmacokinetics of GEM and TAX given weekly in chemo-naive patients with advanced NSCLC. Patients and methods: Escalating doses of GEM (800-2000 mg/m(2)) and TAX (60-100 mg/m(2)) were administered on days 1, 8, 15 every 4 weeks to 35 patients with advanced NSCLC. Plasma pharmacokinetics of TAX and GEM was assessed at the three higher dose-levels. Results: Dose-escalation was discontinued in absence of MTD because of increased cumulative toxicity leading to dose modification or treatment delay at levels 6 and 7 (TAX 100 mg/m(2) plus GEM 1750 and, respectively, 2000 mg/m(2)). Hematological toxicity included grade 4 neutropenia in 3% of cycles, grade 3 thrombocytopenia in one cycle and febrile neutropenia in three cycles. Maximal non-hemathological toxicity was grade 3 elevation in serum transaminases and grade 2 neuro-sensory toxicity in 8% and 5% of cycles, respectively. At the two higher dose-levels a non-linear pharmacokinetics of GEM was observed with a remarkable variability of C-max and AUG. No pharmacokinetic interactions were reported. Objectives responses were seen at all dose levels, with an overall response rate of 43% (95% confidence interval (95% CI): 25.5%-62.6%) in 30 evaluable patients. Conclusions: The weekly administration of GEM and TAX is very well tolerated, and has shown promising antitumor activity in NSCLC. In view of the cumulative toxicity and of the pharmacokinetic profile of GEM, doses of 1500 mg/m(2) of GEM and 100 mg/m2 of TAX are recommended for phase II studies

Factor V leiden mutation in patients with breast cancer with a central venous catheter: risk of deep vein thrombosis

BACKGROUND: The objective of this study was to analyze the influence of the prothrombotic factor V Leiden (FVL) and G20210A prothrombin mutations on the frequency of the first episode of catheter-related deep vein thrombosis (DVT) in a cohort of patients with locally advanced or metastatic breast cancer during continuous venous insult (infusion of 5-fluorouracil-based chemotherapy). PATIENTS AND METHODS: Between January 1999 and February 2001, we retrospectively analyzed the incidence of first DVT in 300 consecutive patients with locally advanced or metastatic breast cancer treated at a single institution with a combination of chemotherapy administered continuously through a totally implanted access port. We identified 25 women (study group) with catheter-related DVT. For each of the 25 patients, we selected 2 women eligible for identical chemotherapy who had similar age, stage of disease, and prognostic features as a control group. The prothrombotic FVL and prothrombin mutation G20210A genotype analyses were performed in all patients. Analyses were performed on blinded samples, and all patients signed a specific informed consent form. A total of 25 cases (with thrombosis) and 50 frequency-matched controls were evaluated for FVL. RESULTS: Five cases and 2 controls were found with the mutation in the FVL, for incidences of 20% (95% CI, 9%-39%) and 4% (95% CI, 1%-14%), respectively. Thus, the frequency of the mutation was significantly higher in the cases than in controls (P = 0.04), and a logistic regression analysis, adjusted by age, yielded an odds ratio of 6.1 (95% CI, 1.1%-34.3%; P = 0.04). Time from start of infusion chemotherapy to thrombosis was not significantly different between those with the mutation (median, 31 days) and without the mutation (median, 43 days; P = 0.6). Only 1 subject (in the case group) was found with the G20210A mutation in the prothrombin gene. CONCLUSION: Factor V Leiden carriers with locally advanced or metastatic breast cancer are at high risk of catheter-related DVT during chemotherapy. Clinicians should be aware of this increased risk, and alternative cytotoxic treatments not requiring continuous infusions should be considered for these patients

The MERITO Study: a multicentre trial of the analgesic effect and tolerability of normal-release oral morphine during 'titration phase' in patients with cancer pain.

Adequate and rapid pain control is one of the main goals of cancer pain treatment. The objective of this study was to assess the effect and tolerability of oral normal-release morphine during the initial phase of treatment in patients with moderate-to-severe cancer pain. Consecutive patients naïve to strong opioids received normal-release morphine 5 or 10 mg every 4 h during the titration phase (first 5 days), depending on previous analgesic therapy. Pain intensity was assessed using an 11-point Numerical Rating Scale (0-10), and data were recorded in a patient-compiled diary. The primary endpoint was the proportion of time with pain control (a reduction of at least 50% with respect to the baseline pain score) during the titration phase. A total of 159 consecutive patients (102 men; mean age 65 years) with cancer-related pain were enrolled. Pain control was observed for 75% (95% CI 70-80) of the follow-up period in the intent-to-treat population. Overall, 50% and 75% of patients achieved pain control within 8 and 24 h after starting normal-release morphine therapy respectively. The mean pain score was 7.63 points at baseline, and decreased to 2.43 and 1.67 points (both P<0.001) at days 3 and 5 respectively. The most commonly reported adverse events were somnolence (24% of patients), constipation (22%), vomiting (13%), nausea (10%) and confusion (7%). Normal-release morphine results in rapid and satisfactory pain control, and is well tolerated, during the strong-opioid titration phase in patients with moderate-to-severe cancer pain

Adventist Millennials: Measuring Emerging Adults’ Connection to Church

© 2018, Religious Research Association, Inc. Numerous research studies have demonstrated an exodus of emerging adults from Christian denominations. The Adventist Connection Study examined how emerging adult graduates of Seventh-day Adventist universities in the United States connect with or disconnect from Adventist churches in the context of identity, community, orthodoxy, and orthopraxy. Through a two-phased mixed methodology approach, researchers conducted semi-structured interviews with self-selected focus groups of recent college graduates, developed an inductively generated survey instrument, and then electronically distributed the survey via email to recent Adventist college graduates. The results suggested several themes for further discussion. Particularly notable is the influence personal religiosity has on the sample’s acceptance of Adventist teachings and faith practice, as well as the negative impact participants’ media usage and transitory lifestyles have on their connection to local churches. Overall, the majority of the sample identified as connected to the Adventist Church, and many who appear to have disconnected from the Adventist Church remain engaged in a variety of nontraditional ways

Normal-release oral morphine starting dose in cancer patients with pain.

OBJECTIVES: To evaluate whether the current European Association for Palliative Care recommendation regarding the starting dose of 5 mg of normal-release morphine (NRM) sulfate oral solution every 4 hours in opioid naive patients or 10 mg in patients already being treated with "weak" opioids is effective and could be proposed as starting routine dose in clinical practice. Secondary aims were to estimate the percentage of patients who were high responders to NRM and to study the association of baseline patient characteristics with both high analgesic responsivity and the need of opioid dose escalation. METHODS: Consecutive strong opioid-naive patients with cancer pain were enrolled in a multicenter uncontrolled phase 4 clinical trial. Oral NRM was administered at 2 different dosages: 5 and 10 mg every 4 hours, respectively, for opioids-naive (group A) and nonopioids-naive (group B) patients as starting therapy. Average daily dosages of NRM and opioid escalation index (OEI) were calculated and the reduction in pain score was tested through Student t test both in group A and in group B patients. RESULTS: One hundred fifty-nine consecutive patients were enrolled and data analysis was conducted on 151 (95%) patients. On an average the OEIs were: 3.2 in group A and 6.5 in group B and a significant reduction in pain score both after 3 and 5 days from baseline (P<0.001) was shown in both groups. In multivariate analysis both Karnofsky Performance Status and episodic pain showed to be independent prognostic factors of a high analgesic response. The presence of neuropathic pain showed to be associated with a higher OEI. DISCUSSION: These data show that empiric standard doses of NRM during titration, recommended by European Association for Palliative Care, are effective in clinical practice