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Background: Mild anemia is a frequent laboratory finding in the elderly usually disregarded in everyday practice as an innocent bystander. The aim of the present population-based study was to prospectively investigate the association of mild grade anemia with hospitalization and mortality., Design and Methods: A prospective population-based study of all 65 to 84 year old residents in Biella, Italy was performed between 2003 and 2007. Data from a total of 7,536 elderly with blood tests were available to estimate mortality; full health information available to evaluate health-related outcomes was available for 4,501 of these elderly subjects. Mild grade anemia was defined as a hemoglobin concentration between 10.0 and 11.9 g/dL in women and between 10.0 and 12.9 g/dL in men., Results: The risk of hospitalization in the 3 years following recruitment was higher among the mildly anemic elderly subjects than among subjects who were not anemic (adjusted hazard ratio: 1.32; 95% confidence interval: 1.09-1.60). Mortality risk in the following 3.5 years was also higher among the mildly anemic elderly (adjusted hazard ratio: 1.86; 95% confidence interval: 1.34-2.53). Similar results were found when slightly elevating the lower limit of normal hemoglobin concentration to 12.2 g/dL in women and to 13.2 g/dL in men. The risk of mortality was significantly increased in mild anemia of chronic disease but not in that due to beta-thalassemia minor., Conclusions: After controlling for many potential confounders, mild grade anemia was found to be prospectively associated with clinically relevant outcomes such as increased risk of hospitalization and all-cause mortality. Whether raising hemoglobin concentrations can reduce the risks associated with mild anemia should be tested in controlled clinical trials.

Today many different drugs are available for treatment of multiple sclerosis (MS). Interferons, glatiramer acetate, mitoxantrone, and natalizumab have been approved by the regulatory authorities of many countries for the treatment of MS. Evidence based medicine (EBM) principles allow physicians to better address the correct treatment for patients. This article aimed to review all the clinical trials on immune-modulating and immunosuppressive drugs on the basis of the EBM principles. Based on the evidence to date interferon beta represents the best therapeutic option, particularly if given at high doses and with multiple injections per week. Due to its lower efficacy, glatiramer acetate should be used as a second choice in case of intolerable side effects or toxicity of interferon beta. Great efficacy has been demonstrated for mitoxantrone and natalizumab. These drugs should be, however, used with particular attention for their potential toxic effects.

We aimed to evaluate the safety and MRI efficacy of interferon beta-1b (IFNbeta-1b) 375 microg (subcutaneously [sc] every other day [eod]) in relapsing-remitting multiple sclerosis (RRMS) patients with a suboptimal response to IFNbeta-1b 250 microg, i.e., with MRI activity or relapses. The OPTimization of Interferon for MS (OPTIMS) study was a prospective multicenter randomized phase 2 trial comprising a 6-month run-in phase (to identify suboptimal responders) and a 6-month randomized phase of open-label clinical and blinded MRI follow-up. During run-in all patients were treated with IFNbeta-1b 250 microg sc eod; during the study phase suboptimal treatment responders were randomized either to IFNbeta-1b 250 or 375 microg sc eod. Primary outcome was the proportion of patients without MRI activity during study Months 9-12 according to the intention-to-treat principle. 216 RRMS patients entered the study: 83 suboptimal responders were identified and randomized, 7 refused to continue treatment, 76 were included in the analysis. More patients treated with 375 microg had no MRI activity at Months 9-12 (30/36 vs.16/40; relative risk, 0.28; 95 % confidence interval, 0.08-0.47; p = 0.0001). Sensitivity analysis ("worst case scenario") confirmed the results. No new or unexpected adverse events were observed, but there was a trend towards more withdrawals in the 375 microg group. Increasing the dose of IFNbeta-1b from 250 microg to 375 microg is a successful strategy for reducing subclinical signs of disease activity in RRMS patients. Further studies are needed to show whether this dose may also improve clinical efficacy.

Objective: To prospectively validate MRI activity and neutralising anti-interferon antibody (NAb) during the first 6 months of interferon beta treatment as response indicators in multiple sclerosis (MS)., Methods: Patients with relapsing-remitting MS were followed during the first 2 years of treatment. Neurological assessments were performed every 3 months or when a relapse was suspected. MRI scans performed at baseline and at 3, 4, 5 and 6 months after the start of treatment were assessed centrally for disease activity: new T2 or gadolinium enhancing T1 lesions. NAb were assessed using the MxA protein assay; positivity was defined as two consecutive titres >or=20 NU/ml. We evaluated the predictivity of an active scan, NAb positivity, or both, during the first 6 months of treatment, on the occurrence of clinical disease activity in the following 18 months., Results: 147 patients were assessed at 16 centres. Predictivity parameters (with confidence intervals) were as follows: active scan, sensitivity (SN) 52% (34-69%), specificity (SP) 80% (65-91%), negative predictive value (NPV) 73% (58-77%), positive predictive value (PPV) 62% (42-79%), p = 0.002; NAb positivity, SN 71% (45-88%), SP 66% (55-76%), NPV 92% (82-97%), PPV 29% (16-45%), p = 0.01; active scan and NAb positivity, SN 71% (38-91%), SP 86% (73-94%), NPV 94% (86-98%), PPV 50% (29-70%), p = 0.0003., Conclusions: MRI activity and NAb occurrence during the first 6 months of interferon beta treatment were reliable predictors of long term clinical response, particularly when combined. Patients with negative predictors showed a less than 10% risk of developing clinical activity. Patients with positive predictors showed a 50% risk of further clinical activity. These patients need to be followed carefully with further MRI and NAb tests.

Background: Immunomodulatory drugs have been shown to be only modestly effective in clinically definite relapsing remitting multiple sclerosis (RRMS). It has been hypothesized that their efficacy could be higher if used at the first appearance of symptoms, that is in the clinically isolated syndromes (CIS) suggestive of demyelinating events, a pathology which carries a high risk to convert to clinically definite MS (CDMS)., Objectives: The objective of this review was to assess the effects of immunomodulatory drugs compared to placebo in adults in preventing conversion from CIS to CDMS which means the prevention of a second attack., Search Strategy: We searched the Cochrane MS Group Trials Register (June 2007), Cochrane Central Register of Controlled Trials (CENTRAL)The Cochrane Library Issue 3, 2007, MEDLINE (January 1966 to June 2007), EMBASE (January 1974 to June 2007) and reference lists of articles. We also contacted manufacturers and researchers in the field., Selection Criteria: The trials selected were double-blind, placebo-controlled, randomised trials of CIS patients treated with immunomodulatory drugs., Data Collection and Analysis: Study selection have been independently done by two reviewers. Two further reviewers independently assessed trial quality and extracted and analysed data. Study authors were contacted for additional informations. Adverse effects information was collected from the trials., Main Results: Only three trials tested the efficacy of interferon (IFN) beta including a total of 1160 participants (639 treatment, 521 placebo); no trial tested the efficacy of glatiramer acetate (GA). The metanalyses showed that the proportion of patients converting to CDMS was significantly lower in IFN beta-treated than in placebo-treated patients both after one year (pooled OR 0.53; 95% CI, 0.40 to 0.71; p <0.0001) as well as after two years of follow-up (pooled OR 0.52; 95% CI, 0.38 to 0.70; p <0.0001). Early treatment with IFN beta was associated with the side effect profile reported by the randomised controlled trials with this drug. Since side effects were reported with some heterogeneity in the three studies the metanalysis was possible only for the frequency of serious adverse events, not significantly different in IFN beta-treated or placebo-treated patients., Authors' Conclusions: The efficacy of IFN beta treatment on preventing the conversion from CIS to CDMS was confirmed over two years of follow-up. Since patients had some clinical heterogeneity (length of follow-up, clinical findings of initial attack), it could be useful for the clinical practice to further analyse the efficacy of IFN beta treatment in different patient subgroups.

Background: In the elderly persons, hemoglobin concentrations slightly below the lower limit of normal are common, but scant evidence is available on their relationship with significant health indicators. The objective of the present study was to cross-sectionally investigate the association of mild grade anemia with cognitive, functional, mood, and quality of life (QoL) variables in community-dwelling elderly persons., Methods: Among the 4,068 eligible individuals aged 65-84 years, all persons with mild anemia (n = 170) and a randomly selected sample of non-anemic controls (n = 547) were included in the study. Anemia was defined according to World Health Organization (WHO) criteria and mild grade anemia was defined as a hemoglobin concentration between 10.0 and 11.9 g/dL in women and between 10.0 and 12.9 g/dL in men. Cognition and functional status were assessed using measures of selective attention, episodic memory, cognitive flexibility and instrumental and basic activities of daily living. Mood and QoL were evaluated by means of the Geriatric Depression Scale-10, the Short-Form health survey (SF-12), and the Functional Assessment of Cancer Therapy-Anemia., Results: In univariate analyses, mild anemic elderly persons had significantly worse results on almost all cognitive, functional, mood, and QoL measures. In multivariable logistic regressions, after adjustment for a large number of demographic and clinical confounders, mild anemia remained significantly associated with measures of selective attention and disease-specific QoL (all fully adjusted p<.046). When the lower limit of normal hemoglobin concentration according to WHO criteria was raised to define anemia (+0.2 g/dL), differences between mild anemic and non anemic elderly persons tended to increase on almost every variable., Conclusions: Cross-sectionally, mild grade anemia was independently associated with worse selective attention performance and disease-specific QoL ratings.

Purpose: The aim of this study was to investigate the efficacy of the combination of irinotecan/cetuximab and to plan related skin toxicity management with an oncologic/dermatologic team., Patients and Methods: Thirty-four patients with epidermal growth factor receptor (EGFR)-expressing metastatic colorectal cancer received cetuximab 400 mg/m2 as an initial dose and 250 mg/m2 weekly thereafter. In addition, patients received irinotecan 180 mg/m2 every 2 weeks., Results: Thirty-two patients were evaluated for response rate (RR) and skin toxicity to establish the best management. In our study, the responses observed with cetuximab treatment were complete response in 1 patient (3%), partial response in 11 patients (34%), disease stabilization in 6 patients (19%), and progressive disease in 14 patients (44%). Of 34 patients evaluable for cutaneous toxicity, 10 patients (29%) presented with grade 1 eruption, 13 (38%) with grade 2 eruption, and 4 (12%) with grade 3 eruption. Allergic reactions such as flushing and urticaria (grade 2) were seen in 2 patients (6%)., Conclusion: Cutaneous reactions consisted of follicular rash, xerosis, painful fissures in palms and soles, alterations in hair growth, and mucositis. In the majority of patients (80%-90%), the worst recorded skin effects were mild (grade 1) to moderate (grade 2). The incidence of severe cases (grade 3) was approximately 15%. All dermatologic effects were reversible and generally without sequelae within 4 weeks after treatment discontinuation. We observed significant correlations between degree of cutaneous toxicity and increased RR. Correct identification and treatment by oncologic/dermatologic cooperation of EGFR cutaneous side effects help to improve quality of life.

Adherence to long-term therapy has always been a problem in all fields of medicine. In multiple sclerosis (MS), treatment consists of parenteral administration of immune-modulating drugs once or several times weekly for an as yet undetermined length of time. Different studies on the MS patients' compliance showed that the most frequent cause of stopping treatment is the perceived lack of efficacy and that most treatment withdrawals occur during the first year of treatment. A trial aimed to identify the minimum effective IFNbeta dose showed that some patients had disease activity after switching to a lower IFNbeta dose. OPTIMS (OPTimization of Interferon dose for MS study) was a multicenter study, involving 24 Italian MS centers, 216 patients, aimed to identify a treatment response indicator allowing the early identification of poorly responding patients. A single active scan during the first 6 months of IFN treatment had a significant positive predictability of 59% (95% confidence interval, 41-76; p=0.05) on the presence of clinical signs of disease activity during the further 2-year follow-up.

Background: Carcinoma of the prostate gland is the most frequent malignant tumour affecting male population. While the large majority of tumours is represented by adenocarcinoma, pure squamous cell carcinoma comprises only 0.5-1% of all prostate neoplastic lesions. It is characterised by a high degree of malignancy, commonly metastasising to the bone (mainly with osteolytic lesions), liver and lungs with a median survival time of 14 months. Several therapeutic approaches have been employed in the effort to treat prostate pure squamous cell carcinoma, including radical surgery, radiotherapy, chemotherapy and hormonal therapy. All of them mostly failed to gain a significant survival benefit., Case Report: We herein report on a case of pure squamous cell carcinoma of the prostate approached with combined-modality treatment, with the administration of 3 courses of cisplatin 75 mg/m(2) on day 1 and continuous infusion 5-fluorouracil 750 mg/m2 on day 1 to 5 and, subsequently, radiotherapy, with the delivery of a total dose of 46 Gy to the whole pelvis, with additional boost doses of 20 Gy to the prostatic bed and adjunctive 6 Gy to the prostate gland (72 Gy in total). The patient remained free of disease for 5 years, finally experiencing local relapse and, subsequently, dying of acute renal failure due to bilateral uretero-hydro-nephrosis. In addition, we provide a complete overview of all reported cases available within the medical literature., Conclusion: Since it remains questionable which should be the most appropriate therapeutic approach towards prostate pure squamous cell carcinoma, our report demonstrates that a prolonged disease control, with a consistent survival time, may be achieved by the combination of an effective local treatment such as radiotherapy with systemic infusion of chemotherapeutic drugs.

At present, two types of recombinant human interferon (IFN)-beta are in clinical use. IFN-beta1a is produced in genetically engineered Chinese hamster ovary cells, and its amino acid sequence and glycosylation pattern are identical to those of endogenous human IFN-beta. The beneficial effect of IFN-beta in multiple sclerosis (MS) probably results from different mechanisms of action, such as a direct effect on plasma cells modulating IgG synthesis, an increase of interleukin (IL)-10 levels, the inhibition of IL-1beta and tumour necrosis factor alpha, the stimulation of IL-1 receptor antagonist production, the inhibition of proliferation of leukocytes, a decreased antigen presentation in microglia, a reduction of T cell migration into the brain by inhibition of the activity of T cell matrix metalloproteinases, and a downregulation of adhesion molecules. IFN-beta1a has been shown by several multicenter controlled trials to be effective in relapsing-remitting MS. It reduces relapse rate by 30-50%, magnetic resonance imaging signs of disease activity in 30-80% and disability progression by 30%. It is also effective in preventing conversion to clinically definite MS when given at the time of a first demyelinating event (i.e., at the very beginning of the clinical disease). No clear evidence of the persistence of the efficacy over the long-term has stood out from a systematic analysis of published trials. A Cochrane review concluded that, in fact, the clinical effect beyond the first year of treatment is not clear. Finally, no efficacy has been shown in secondary progressive or primary progressive MS. However, IFN-beta1a is very well tolerated and the most frequent side effects are mild (local skin reaction and flu-like symptoms) and decline in frequency or disappear after the first 3-6 months of treatment. Although the optimal frequency between once weekly or multiple weekly administrations is still controversial, all protocols require multiple monthly injections. Some patients might find it hard to cope with such a treatment regimen over the long term. Ongoing trials with new powerful immunomodulatory drugs, such as monoclonal antibodies, that require only monthly or bimonthly parenteral administrations will probably offer a better tolerated treatment option in the near future.

Background: In RRMS, clinical exacerbations are usually associated with different types of active lesions at MRI, including: hyperintense lesions on T1-weighted post-gadolinium sequences; new hyperintense lesions or enlarging old lesions on PD/T2-weighted scans; or new hypointense lesions on T1-weighted pre-Gd sequences., Objective/methods: Primary outcome was the occurrence of patients with at least one active MRI lesion of the different types indicated above during treatment with 250 microg every other day (EOD) interferon beta (IFNbeta)-1b or 30 microg once weekly (OW) IFNbeta-1a in outpatients with RRMS (INCOMIN Trial)., Results: The number of patients with at least one 'active' lesion, evaluated over the two-year follow-up, was significantly (P = 0.014) lower in the EOD IFNbeta-1 b arm (1 3/76, 17%) then in the OW IFNbeta-1a arm (25/73, 34%). NAb frequency over two-year follow-up was 22/65 (33.8%) in the EOD IFNbeta-1b arm and 4/62 (6.5%) in the OW IFNbeta-1a arm, significantly greater in the EOD IFNbeta-1b arm., Conclusions: The development of MRI active lesions is strongly reduced by EOD-IFNbeta-1b compared with OW-IFNbeta-1a, indicating that EOD-IFNbeta-1b is more effective than OW-IFNbeta-1a in reducing ongoing inflammation and demyelination in MS. Logistic regression showed that NAb status did not affect the risk of MRI activity.

The INCOMIN study (INdependent COMparison of INterferons) lends further support to the growing body of evidence that both dose and frequency of interferon beta (IFNbeta) administration are important in the treatment of multiple sclerosis (MS). High-dose, high-frequency IFNbeta (IFNbeta-1b 250 microg eod sc and IFNbeta-1a 44 microg sc) treatment offers greater therapeutic benefit, in terms of clinical and magnetic resonance imaging (MRI) outcome measures, compared with low-dose, once-weekly administration of IFNbeta. The importance of maintaining the most effective treatment regimen has been shown in another study. The data from this study suggested that patients who have 'stable' disease (i. e. no evidence of clinical or MRI disease activity) during long-term treatment with IFNbeta-1b 250 microg, who are subsequently treated with low-dose, once-weekly IFNbeta-1a 30 microg, are more likely to experience relapses, disease progression or MRI activity compared with those remaining on IFNbeta-1b 250 microg. These data clearly indicate that frequently administered therapy must be maintained to achieve the optimal therapeutic benefit for patients. Those patients who had their IFNbeta-1b 250 microg therapy reduced to low-dose, once-weekly IFNbeta-1a and experienced a resumption of disease activity were returned to their previous regimen. However, after 1 year of additional follow-up, many of these patients still had clinical or MRI signs of disease activity, highlighting further the risks associated with the reduction of IFNbeta dose and frequency of administration. Taking into consideration the evidence supporting the greater efficacy of IFNbeta-1b 250 microg or IFNbeta-1a 44 microg in MS it is of considerable interest to examine whether it is useful to increase the dose of IFNbeta-1b in patients who do not respond satisfactorily to the approved standard dose. This is the rationale for the recently completed OPTIMS (OPTimization of Interferon for MS) study, in which partially responding patients were randomised to IFNbeta-1b 250 or 375 microg every other day. An interim safety analysis of OPTIMS patients has not raised any safety or tolerability concerns. In summary, there is consistent evidence to support the importance of maintaining frequently administered IFNbeta (IFNbeta-1b 250 microg or IFNbeta-1a 44 microg) for the treatment of MS.

Long-term trials have demonstrated the continued efficacy of interferon (IFN) beta treatment in patients with relapsing-remitting (RR) multiple sclerosis (MS) during prolonged administration. The objective of the work was to evaluate the effects of reducing IFN beta administration frequency and total weekly dose in patients with RR MS who have achieved clinical and MRI disease activity stabilization during long-term IFN beta-1b treatment. Prospective 1-year follow-up of 27 RR MS patients on long-term 250 microg every other day (standard dose) IFN beta-1b treatment were randomized either to gradually reduce dose to 30 microg once-a-week IFN beta-1a (13 patients), or to continue on IFN beta-1b standard dose (14 patients). We found significant differences in the two group of patients. In the group of patients continuously treated with IFN beta-1b standard dose, 79% remained relapse free compared to 23% in the group receiving once-weekly IFN beta-1a (p=0.006). The number of patients without new PD/T2 lesions was higher in the group of patients continuously treated with IFN beta-1b standard dose (77%) compared to the once-weekly IFN beta-1a group (23%) (p=0.04). IFN beta is a long-term treatment for MS. The reduction of IFN beta-1b administration frequency and dose is not advisable even in patients free from clinical and MRI disease activity for many years.

Cancer relate fatigue is one of the most frequent problems among cancer patients. It is a nosological highly debilitating entity which has very negative effects on patients quality of life. Foreign literature reports that only during last years oncological operators have started getting aware and their training in order to face it is lacking. Our research wants to propose and analysis of the Italian reality by sending to oncological doctors and nurses a quationnaire. This questionnaire allowed to demonstrate that oncological operators have started knowing the fatigue problem but they are still unprepared about knowledge, professional capability and organizational modalities which could allow a better and efficacius approach to the fatigue problem. We think that research and professional training are the two ways which we will allow to gain knowledge and proper instruments in order to provide for our patients'needs.

Interferon beta (IFN-beta) reduces exacerbation rates in patients with relapsing-remitting multiple sclerosis (MS), but some patients do not respond to treatment. Recent studies have shown a clear dose-response effect on the reduction of exacerbation rates, and on burden of disease accumulation and active lesion frequency seen on MRI. During treatment with 8 MIU IFN-beta we noticed a 30% rate of treatment failure. We then treated non-responders with 12 MIU IFN-beta and observed significant improvement in the clinical signs of disease activity. In order to compare the efficacy of two different doses of IFN-beta-1b, a multicenter study for the optimization of interferon for MS (OPTIMS) has been organized. The design of the study is presented here.

Purpose: Approximately 60% of patients with small-cell lung cancer (SCLC) develop brain metastases. Whole-brain radiotherapy (WBRT) gives symptomatic improvement in more than 50% of these patients. Because brain metastases are a sign of systemic progression, and chemotherapy was found to be effective as well, it becomes questionable whether WBRT is the only appropriate therapy in this situation., Patients and Methods: In a phase III study, SCLC patients with brain metastases were randomized to receive teniposide with or without WBRT. Teniposide 120 mg/m(2) was given intravenously three times a week, every 3 weeks. WBRT (10 fractions of 3 Gy) had to start within 3 weeks from the start of chemotherapy. Response was measured clinically and by computed tomography of the brain., Results: One hundred twenty eligible patients were randomized. A 57% response rate was seen in the combined-modality arm (95% confidence interval [CI], 43% to 69%), and a 22% response rate was seen in the teniposide-alone arm (95% CI, 12% to 34%) (P<.001). Time to progression in the brain was longer in the combined-modality group (P=.005). Clinical response and response outside the brain were not different. The median survival time was 3.5 months in the combined-modality arm and 3.2 months in the teniposide-alone arm. Overall survival in both groups was not different (P=.087)., Conclusion: Adding WBRT to teniposide results in a much higher response rate of brain metastases and in a longer time to progression of brain metastases than teniposide alone. Survival was poor in both groups and not significantly different.

This pilot study was conducted to evaluate the advantage in drug delivery for regional chemotherapy in patients with unresectable recurrent rectal carcinoma by different methods. For this research, the pharmacokinetic advantages of mitomycin C delivery by four different methods were compared: intraaortic infusion with aortic stopflow; intraaortic infusion with inferior vena cava stopflow; intraaortic infusion with aortic and inferior caval vein stopflow (hypoxic pelvic perfusion); and hypoxic pelvic perfusion with hemofiltration. The results of this study indicate that pelvic stopflow infusion followed by hypoxic pelvic perfusion significantly increases mitomycin C concentrations in the blood coming from the tumor site. Also, use of hemofiltration reduces mitomycin C levels in peripheral blood after high-dose regional chemotherapy. Further investigations involving more patients should be carried out in the future to validate these results.

Background: Thymomas are rare neoplasms of the mediastinum. The role of chemotherapy in advanced thymomas is not fully established., Patients and Methods: In the European Organization for Research and Treatment of Cancer (EORTC) Lung Cancer Cooperative Group, 16 patients with recurrent or metastatic malignant thymoma were entered over 6 years onto a study of combination chemotherapy that consisted of cisplatin 60 mg/m2 on day 1 and etoposide 120 mg/m2 on days 1, 2, and 3, every 3 weeks., Results: A median of six courses per patient was administered. Main side effects of treatment were leukopenia, nausea and vomiting, and alopecia. Five complete responses and four partial responses were obtained, with a median response duration of 3.4 years. The median progression-free survival and survival times were 2.2 years and 4.3 years, respectively, with a median follow-up duration of 7 years., Conclusion: The combination of cisplatin and etoposide is highly effective and well tolerated in advanced thymoma. The investigation of this combination in a neoadjuvant setting in unresectable invasive thymoma is warranted.

Purpose: We conducted a randomized trial to investigate the value of the addition of cisplatin to teniposide (VM26) and to investigate the schedule dependence of the topoisomerase II inhibitor VM26, in advanced non-small-cell lung cancer (NSCLC) patients., Patients and Methods: Two hundred twenty-five NSCLC patients were randomized to receive VM26 120 mg/m2 on days 1, 3, and 5 or 360 mg/m2 on day 1 only, either as a single drug or in combination with cisplatin 80 mg/m2 on day 1. Cycles were repeated every 3 weeks. Response rates, side effects, and survival were compared according to the 2 x 2 factorial design of this study., Results: The response rate of the two cisplatin-containing arms was superior to that of the two arms that contained VM26 only (22% v 6%, P < .001); progression-free survival and survival times were also longer in the cisplatin-containing arms (median, 4.3 v 2.2 months, P = .003; median 7.2 v 5.9 months, P = .008, respectively). Toxicity was significantly higher in the cisplatin-containing arms; the most frequent side effects were leukopenia, nausea and vomiting, and alopecia. The schedule of VM26 did not significantly influence the response rate, progression-free survival interval, or survival duration. However, the response rate of the 1-day administration was significantly lower than that of the 3-day administration when given as single drugs., Conclusion: The addition of cisplatin to VM26 improves the response rate, progression-free survival interval, and survival duration over VM26 alone, although at the cost of a significant increase in toxicity. Cisplatin should be considered as the basis for combination chemotherapies in advanced NSCLC.

The activity and toxicity of a carboplatin (300 mg/m2, day 1) and methotrexate (50 mg/m2, days 8 and 15) combination chemotherapy in the treatment of advanced urothelial cancer (UC) was evaluated in the present study. A total of 49 patients entered the study: 44 patients were evaluable for response, and 48 for toxicity. A complete response (CR) was found in 4/44 patients (9.1%) and a partial remission (PR) in 12/44 patients (27.2%) for an overall response rate of 16/44 (36.3%). Stable disease was found in 21/44 patients (47.7%), and progressive disease in 7/44 patients (15.9%). Survival was significantly longer in responding patients than nonresponders (median: 62 weeks vs 50 weeks, P < .05). Hematologic and renal toxicities were mild, thrombocytopenia and leukopenia being the most relevant side effects. The first consecutive 7 patients received methotrexate also on day 22; 5 of them underwent grade III-IV hematologic toxicity, so methotrexate on day 22 was omitted in the subsequent patients. No toxic deaths were reported. CBDCA and MTX combination chemotherapy is well tolerated and moderately active in the treatment of advanced urothelial cancer and may represent a valid alternative to cisplatin-containing regimens in patients with poor performance status and/or impaired renal function.

From April 1991 to September 1993, 18 patients affected by a presumed operable IIIa (N2) non small cell lung cancer (NSCLC) with histologically confirmed bulky mediastinal metastases, received preoperative concurrent radiation therapy and continuous infusion of cisplatinum (CDDP). The radiotherapy consisted of 2 Gy given 5 days a week for a total dose of 50 Gy; CDDP was administered by means of a central catheter and a portable pump at the daily dose of 6 mg/m2 given on the same days as the radiation therapy (total dose: 150 mg/m2). Two weeks after the end of the treatment, the patients were reevaluated: 5 patients had either local or distant disease progression, the other 13 were submitted to thoracotomy: 12 received a complete resection and 1 patient underwent only a mediastinal lymphadenectomy, because pneumonectomy was impossible due to lack of respiratory function. No histological evidence of cancer cells was observed in the specimens of 6 patients (33%). Radiological response rate was 61% (11/18); resection rate was 66% (12/18) and complete resection rate was 61% (11/18). There was one postoperative death (5%). The 3 year actuarial survival rate is 63.6% for the patients who received a resection with a median survival time of 18 months. All non operated patients died within one year. Combined preoperative treatment was well tolerated. Better results were achieved in patients with squamous cell carcinoma who had a complete resection following a total tumor sterilization with radio-chemotherapy.

Background: The EORTC Head and Neck Cancer Cooperative Group conducted a randomized comparison of cisplatin, methotrexate, bleomycin and vincristine (CABO) versus cisplatin and 5-fluorouracil (CF) versus cisplatin (C) in chemotherapy naive patients with recurrent or metastatic squamous cell carcinoma of the head and neck. The primary objectives of this study were to investigate whether the CF regimen was in anyway superior to the CABO regimen and to detect any superiority of these two combinations over cisplatin alone., Patients and Methods: Three hundred eighty-two patients were randomized to one of three treatments: (1) methotrexate (40 mg/m2) days 1 and 15, bleomycin (10 mg) and vincristine (2 mg) days 1, 8 and 15, cisplatin (50 mg/m2) day 4, repeated every 21 days, (2) cisplatin (100 mg/m2) and 5-FU (1 g/m2 x 4), repeated every 21 days, and (3) cisplatin (50 mg/m2) days 1 and 8, repeated every 28 days. After 3 cycles, all responding and stable disease patients in the three arms of the study continued with cisplatin alone., Results: The overall response rates to CABO (34%) and CF (31%) were superior to C (15%) (p < 0.001, p = 0.003, respectively). In addition, complete response rate to CABO (9.5%) was superior to that of C (2.5%) (p = 0.02), and also superior to that of CF (1.7%) (p = 0.01). Response was associated with performance status and prior treatment, but by multivariate analysis treatment type was the important determinant of response (p = 0.0006). Although CABO and CF were superior to C with respect to time to progression within the first 6 to 8 months after randomization, there was no overall difference in progression-free survival or survival between the three arms of the study. Both hematologic and non-hematologic toxicity were worse in the combination chemotherapy arms., Conclusion: We conclude that the CF regimen has no advantage over the CABO regimen, which in fact showed a higher complete response rate. Both combinations showed improved response rates but also more toxicity and no improvement in overall survival in comparison with cisplatin alone.

Aims and Background: It has been suggested that lorazepam has a definite role as an antiemetic drug in antiemetic cocktails. In this study we examined the antiemetic efficacy of metoclopramide (200 mg) and methylprednisolone (1000 mg) with or without lorazepam., Methods: Sixty patients treated with cisplatin-containing regimens were entered into a randomized, double-blind study with cross-over. Lorazepam 2.5 mg or placebo were administered orally the evening before therapy and just after the beginning of fluid infusion for chemotherapy. Degree of nausea and number of vomiting episodes, together with somnolence, were recorded on a data flow sheet and visual-analogue scales., Results: 100 cycles (50 patients) are evaluable. In 39 cycles there was no nausea and vomiting, in 74 cycles acceptable control of emesis was reached (0-2 episodes of vomiting), without significant differences among the two arms. However, nausea was shorter in lorazepam arm (p < 0.01), and 80% of the patients preferred treatment with lorazepam (p < 0.003). Anxiety was reduced in the patients treated with lorazepam (p < 0.4)., Conclusions: Lorazepam improves tolerability to cisplatin-containing chemotherapy, mainly by influencing the psychological status of the patient and favoring the amnestic process.

Preoperative integrated neo-adjuvant radio-chemotherapy was performed in 8 patients suffering from NSCLC bronchial carcinoma at stages IIIA-IIIB (N3 mediastinal). After treatment, 7 patients underwent apparently radical pulmonary exeresis, whereas the patient with adenocarcinoma (T2 N2 M0) was not operated due to the recurrence of disease following supraclavicular lymph node metastasis. Preoperative radio-chemotherapy allows the sub-staging of the disease and the insertion of these patients into the operating programme.

Bone marrow plasma cell labeling index (L.I.), kappa/lambda ratio, CD4+ and CD8+ subpopulations were studied in patients with smoldering multiple myeloma (SMM), active myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS). The loss of the light chain isotype suppression (LCIS) and a high labeling index (L.I.) allowed us to distinguish all MM patients from SMM patients. On the contrary, a low L.I. and a normal kappa/lambda ratio were found in most kappa and lambda MGUS. A significant difference in the kappa/lambda ratio was noted between MGUS and K-SMM. A significant decrease in CD4+ and a significant increase in CD8+ were not observed in patients with LCIS. The kappa/lambda ratio together with the plasma cell L.I. could be useful parameters for distinguishing active MM from SMM, especially in the cases with a border line L.I.

Sixty-one patients undergoing treatment with cis-platin-containing regimens were given prophylactically either metoclopramide or methylprednisolone, in order to reduce the gastrointestinal side effects. Vomiting occurred in 79% of the cycles (128/162), and had a distressing intensity in 39.5% of cycles (64/162). No significant differences were observed between metoclopramide and methylprednisolone with respect to number and duration of vomiting episodes and duration of nausea and anorexia. Two of 6 patients benefited from substitution of metoclopramide for methylprednisolone; only 1/11 benefited from the substitution of methylprednisolone for metoclopramide. Metoclopramide and methylprednisolone, at the dosage and schedule used, were well tolerated and moderately active in preventing nausea and vomiting induced by cis-platin; their use in combination could further improve these results.

Fungal opportunistic infections are a danger for immunocompromised hosts, such as patients with malignancies, especially in a hospital environment. We studied a group of patients with solid tumors of the respiratory tract on admission and after twenty days of hospitalization. Colonization by moulds and/or yeasts was frequently found. Preventive measures should be applied to avoid colonization inside the hospital. The importance of overcrowding, sanitation and diet is pointed out.

We tested 4'-epi-doxorubicin (epirubicin) in 15 patients with advanced squamous cell carcinoma of the head and neck which progressed after conventional therapy. The drug was administered at the dosage of 25 mg/m2 weekly. No patient achieved objective response. Toxicity was minimal. Epirubicin given at this dose and schedule revealed no activity in heavily pretreated patients with cancer of the head and neck.