Elaboration of the preliminary Rheumatoid Arthritis Impact of Disease (RAID) score: a EULAR initiative.

BACKGROUND: Current response criteria in rheumatoid arthritis (RA) usually assess only three patient-reported outcomes (PROs): pain, functional disability and patient global assessment. Other important PROs such as fatigue are not included. OBJECTIVE: To elaborate a patient-derived composite response index for use in clinical trials in RA, the RA Impact of Disease (RAID) score. METHODS: Ten patients identified 17 domains or areas of health relevant for inclusion in the score, then 96 patients (10 per country in 10 European countries) ranked these domains in order of decreasing importance. The seven most important domains were selected. Instruments were chosen for each domain after extensive literature research of psychometric properties and expert opinion. The relative weight of each of the domains was obtained from 505 patients who were asked to "distribute 100 points" among the seven domains. The average ranks of importance of these domains were then computed. RESULTS: The RAID score includes seven domains with the following relative weights: pain (21%), functional disability (16%), fatigue (15%), emotional well-being (12%), sleep (12%), coping (12%) and physical well-being (12%). Weights were similar across countries and across patient and disease characteristics. Proposed instruments include the Health Assessment Questionnaire and numerical ratings scales. CONCLUSION: The preliminary RAID score is a patient-derived weighted score to assess the impact of RA. An ongoing study will allow the final choice of questionnaires and assessment of validity. This score can be used in clinical trials as a new composite index that captures information relevant to patients.

Clinical and pharmacokinetic phase II study of pegylated liposomal doxorubicin and vinorelbine in heavily pretreated recurrent ovarian carcinoma.

BACKGROUND: This multicenter phase II study evaluated feasibility, clinical efficacy, toxicity and pharmacokinetics of the combination of pegylated liposomal doxorubicin (PLD) and vinorelbine (VNR) in patients with platinum-paclitaxel pretreated recurrent ovarian cancer. PATIENTS AND METHODS: All patients received prior treatment with platinum and paclitaxel. Thirty-two heavily pretreated (median number of chemotherapy regimens two, range one to six) ovarian cancer patients received treatment with PLD 30 mg/m(2) and VNR 30 mg/m(2) every three weeks for six cycles. Ten patients entered the pharmacokinetic study, five receiving the PLD-VNR and five the VNR-PLD sequence. RESULTS: In 30 patients evaluated for response and toxicity, the overall response rate was 37% and 10% of patients achieved stable disease. Median time to progression and overall survival were 5.5 months (range 1-10) and 9 months (range 2-16), respectively. Toxicity was generally mild and reversible. VNR AUC(tot) and plasma levels were considerably higher in the PLD-VNR sequence. CONCLUSIONS: The PLD-VNR regimen exhibits significant activity in heavily pretreated patients, is well tolerated and is associated with encouraging survival. Preliminary pharmacokinetic results suggest the PLD-VNR sequence for further clinical applications. This regimen should be considered as a treatment option in patients with chemotherapy-resistant ovarian cancer.

Gemcitabine plus cisplatin in the treatment of patients with advanced non-small cell lung cancer: a phase II study.

BACKGROUND: Lung cancer is the leading cause of cancer death in men worldwide; most cases are not suitable for radical surgery at diagnosis and palliative treatment remains the primary goal of therapy. Cisplatin and gemcitabine are among the most active cytotoxic agents for the treatment of non-small cell lung cancer (NSCLC): they have non-overlapping toxicity and preclinical studies have demonstrated their potential synergistic interaction. PATIENTS AND METHODS: The aims of the present study were to assess the activity and tolerability of cisplatin 80 mg/m2 on day 1, combined with gemcitabine 1000 mg/m2 on days 1 and 8, administered every 3 weeks. A total of 46 consecutive patients with advanced NSCLC entered this study; all of them were evaluable for toxicity and for activity. RESULTS: According to an intent-to-treat analysis, 15 patients attained a partial response (33%), 9 (20%) obtained a disease stabilisation and 22 (47%) progressed. This regimen appeared to be modestly toxic, with grades 3-4 leukopenia and thrombocytopenia observed in 10% and 6% of cases respectively; grade 3 vomiting appeared in 12 patients (26%) and grade 3 mucositis in 1 patient. The median time-to-progression and overall survival were 200 and 400 days, respectively. CONCLUSION: Our study of gemicitabine + cisplatin on stage IV NSCLC patients achieved favourable results in terms of toxicity and overall survival.

Low dose carboplatin (AUC 4.5) combined with vinorelbine in the treatment of advanced non-small cell lung cancer: a single institution phase II study.

Platinum compounds and vinorelbine (VNB) are active in the treatment of non-small cell lung cancer (NSCLC), but moderate toxicity has been reported. The aims of the present study were to assess activity and tolerability of low dose carboplatin (CBDCA): 4.5 AUC according to Calvert formula on day 1, combined with vinorelbine: 25 mg/m2 on days 1 and 8, administered every 4 weeks. Eighty-five advanced NSCLC patients entered the study; all of them were evaluable for toxicity and 83 were evaluable for activity. According to an intent to treat analysis, 26 patients attained a partial response (30.5%; 95% CI 20.5-40.5), 27 (31.7%) obtained a disease stabilization and 30 (35%) progressed. This regimen appeared to be modestly toxic, grade 3-4 leukopenia and thrombocytopenia were observed in less than 5% of cases and grade 2 neuropathy in 10% of cases. Median time to progression and overall survival were 7 and 9 months, respectively. In conclusion, low dose CBDCA (administered following Calvert's formula) and VNB combination is an active and very well tolerated cytotoxic regimen in the treatment of advanced NSCLC. The application of the Calvert formula may have contributed to limit the side effects related to CBDCA.

[Genetic damage in human tumors associated with particular behavioral or occupational exposures]. / Il danno genetico nei tumori umani associati a particolari esposizioni voluttuarie o professionali.

We have conducted a review of the literature on chemical exposures (known carcinogens), mutations in oncogenes/tumor suppressor genes and the occurrence of malignancies. The underlying hypothesis of the studies on this issue is that specific carcinogenic chemicals induce specific mutations in relevant genes ("fingerprints") and that the latter are involved in the causal pathway that leads to cancer. The confirmation of such hypothesis is conditioned by limitations of the available techniques, and by the design of the epidemiological studies. We discuss methodological problems inherent in the identification of oncogene mutations within studies in humans, such as the limited sensitivity of molecular techniques, which may lead to a bias toward the null. Although several studies--concerning mainly lung or bladder cancer and tobacco smoking or some occupational exposures--give support to the theory of "fingerprints", further evidence is warranted.

Value of Ki-67 immunostaining in preoperative biopsies of carcinomas of the lung.

In lung carcinomas, the proliferative activity, as detected by Ki-67 antigen immunostaining of surgical specimens, is a valuable factor predicting clinical evolution and response to treatment. We investigated whether bronchial endoscopic and fine-needle aspiration (FNA) biopsies of lung carcinoma can provide a reliable estimation of the tumor proliferative fraction (TPF). In 66 resectable lung carcinomas, sections of preoperative bronchial or FNA biopsies and the corresponding surgical specimens were stained in parallel for Ki-67 using MIB-1 monoclonal. The mean TPF was 44.7% in the surgical specimens, 40.3% in bronchial biopsies, and 26.3% in FNAs. When the scores of biopsy and resected specimen of each individual tumor were compared, a significant correlation between the TPFs of preoperative and postoperative specimens was found (r = .79). In both biopsy and surgical specimens, a high TPF was associated with squamous cell carcinoma histological type and high-grade (poorly differentiated) tumors. In addition, a significantly (P < .05) lower disease-free interval was found in patients affected by highly proliferating tumors (irrespective of the tumor stage). We conclude that the proliferative activity of lung cancer can be reliably assessed in bronchial or FNA biopsies. This information could help to select chemotherapy protocols in nonresectable lung carcinomas.

Multicenter Phase II trial of intermediate dose cisplatin and vinorelbine in inoperable non-small cell lung cancer patients.

Vinorelbine (VNB) and cisplatin (CDDP) combination regimen was found active in the treatment of advanced non-small cell lung cancer (NSCLC) patients, but significant toxicity was observed. We evaluated the activity and toxicity of this combination administered at lower doses than previously reported. From March 1992 to March 1994, 99 patients (pts) were enrolled in a multicentric Phase II study and received intravenous CDDP at 80 mg/m2 on day 1, associated with intravenous VNB at 25 mg/m2 on days 1 and 8. Cycles were repeated every 3 weeks. The reduced doses led to a consistently lower myelotoxicity (8% Grade III-IV leukopenia) in comparison to two related Phase III studies, recently published. Conversely, the incidence of neurological toxicity was superimposable. Considering all eligible patients, the overall response rate was 28.3%, and this is similar to the results commonly observed employing the most active CDDP containing regimens. In conclusion, CDDP and VNB combination chemotherapy at the schedule performed in the present study led to a reduction of hematologic toxicity, while an appreciable activity was maintained.

Non small cell lung cancer treatment with vinorelbine monochemotherapy: a phase II study.

Non small cell lung cancer is one of the leading causes of death in the industrial countries and some 70% of patients have non surgically eradicable disease. Platinum based combined regimens can achieve 35-40% objective responses, but advanced age, low performance status and concurrent diseases can exclude up to 60% of patients from an adequate poliychemotherapy treatment.

[A clinical analysis of a group of Down's patients]. / Analisi clinica di un gruppo di pazienti Down.

The authors report their experience of the clinical analysis of 40 handicapped subjects: 28 suffered from various degrees of mental handicap and 12 had Down's syndrome. In particular, the authors focused their attention on anomalies of the stomatognathic apparatus in Down subjects, and examined and compared all those factors which are normally attributed to this pathology. An analysis of these findings shows a heterogeneity of clinical conditions which is not revealed in the literature. In the light of these new experiences, before applying pre-programmed protocols in Down's patients it is important to carry out a careful control of their dental, muscular and functional situation together with the prospects for growth and development.

Non small cell lung cancer treatment with carboplatin and vindesine: a phase II study.

A phase II trial aiming to verify the effectiveness of a regimen including carboplatin and vindesine was performed. From November 1989 to September 1990, nineteen patients with advanced small cell lung cancer entered this study. Polychemotherapy treatment included: carboplatin 400 mg/sm, on day 1 and vindesine 3 mg/sm, on days 1 and 15, repeated every 4 weeks, as an outpatient regimen. Observed toxicity was mild; myelodepression, and nausea and vomiting were the main adverse events. No objective response was obtained; 14 no changes in the disease and 4 progressions were detected. The low objective response rate observed in this study is strongly influenced by a set of unfavourable prognostic factors. The median overall survival time [32 weeks] is comparable with the results of other studies.