Do patients' and referral centers' characteristics influence multiple sclerosis phenotypes? Results from the Italian multiple sclerosis and related disorders register.

BACKGROUND: Multiple sclerosis (MS) is characterized by phenotypical heterogeneity, partly resulting from demographic and environmental risk factors. Socio-economic factors and the characteristics of local MS facilities might also play a part. METHODS: This study included patients with a confirmed MS diagnosis enrolled in the Italian MS and Related Disorders Register in 2000-2021. Patients at first visit were classified as having a clinically isolated syndrome (CIS), relapsing-remitting (RR), primary progressive (PP), progressive-relapsing (PR), or secondary progressive MS (SP). Demographic and clinical characteristics were analyzed, with centers' characteristics, geographic macro-areas, and Deprivation Index. We computed the odds ratios (OR) for CIS, PP/PR, and SP phenotypes, compared to the RR, using multivariate, multinomial, mixed effects logistic regression models. RESULTS: In all 35,243 patients from 106 centers were included. The OR of presenting more advanced MS phenotypes than the RR phenotype at first visit significantly diminished in relation to calendar period. Females were at a significantly lower risk of a PP/PR or SP phenotype. Older age was associated with CIS, PP/PR, and SP. The risk of a longer interval between disease onset and first visit was lower for the CIS phenotype, but higher for PP/PR and SP. The probability of SP at first visit was greater in the South of Italy. DISCUSSION: Differences in the phenotype of MS patients first seen in Italian centers can be only partly explained by differences in the centers' characteristics. The demographic and socio-economic characteristics of MS patients seem to be the main determinants of the phenotypes at first referral.

Sexual dysfunction in multiple sclerosis: The impact of different MSISQ-19 cut-offs on prevalence and associated risk factors.

BACKGROUND: Although multiple sclerosis (MS) Intimacy and Sexuality Questionnaire-19 (MSISQ-19) is a widely applied tool, no unique definition of sexual dysfunction (SD) based on its score exists. OBJECTIVE: To explore the impact of different MSISQ-19 cut-offs on SD prevalence and associated risk factors, providing relevant information for its application in research and clinical settings. METHODS: After defining SD according to two different MSISQ-19 cut-offs in 1155 people with MS (pwMS), we evaluated SD prevalence and association with sociodemographic and clinical features, mood status and disability via logistic regression. RESULTS: Depending on the chosen cut-off, 45% to 54% of pwMS reported SD. SD defined as MSISQ-19 score >30 was predicted by age (OR=1.01, p=0.047), cognition (OR=0.96, p=0.004) and anxiety (OR=1.03, p=0.019). SD defined as a score >3 on any MSISQ-19 item was predicted by motor disability (OR=1.12, p=0.003) and cognition (OR= 0.96, p=0.002). CONCLUSION: Applying different MSISQ-19 cut-offs influences both the estimated prevalence and the identification of risk factors for SD, a finding that should be considered during study planning and data interpretation. Preserved cognition exerts a protective effect towards SD regardless from the specific study setting, representing a key point for the implementation of preventive and therapeutic strategies.

Digital therapeutics in neurology.

Digital therapeutics (DTx) is a section of digital health defined by the DTx Alliance as "delivering evidence-based therapeutic interventions to patients that are driven by software to prevent, manage, or treat a medical disorder or disease. They are used independently or in concert with medications, devices, or other therapies to optimize patient care and health outcomes". Chronic disabling diseases could greatly benefit from DTx. In this narrative review, we provide an overview of DTx in the care of patients with neurological dysfunctions.

Real-life impact of early interferon beta therapy in relapsing multiple sclerosis.

OBJECTIVE: Recent findings support greater efficacy of early vs. delayed interferon beta (IFNbeta) treatment in patients with a first clinical event suggestive of multiple sclerosis (MS). We aimed to evaluate the effectiveness of early IFNbeta treatment in definite relapsing-remitting MS (RRMS) and to assess the optimal time to initiate IFNbeta treatment with regard to the greatest benefits on disability progression. METHODS: A cohort of 2,570 IFNbeta-treated RRMS patients was prospectively followed for up to 7 years in 15 Italian MS Centers. A Cox proportional hazards regression model adjusted for propensity score (PS) quintiles was used to assess differences between groups of patients with early vs. delayed IFNbeta treatment on risk of reaching a 1-point progression in the Expanded Disability Status Scale (EDSS) score, and the EDSS 4.0 and 6.0 milestones. A set of PS-adjusted Cox hazards regression models were calculated according to different times of treatment initiation (within 1 year up to within 5 years from disease onset). A sensitivity analysis was performed to assess the robustness of findings. RESULTS: The lowest hazard ratios (HRs) for the three PS quintiles-adjusted models were obtained by a cutoff of treatment initiation within 1 year from disease onset. Early treatment significantly reduced the risk of reaching a 1-point progression in EDSS score (HR = 0.63; 95% CI = 0.48-0.85; p < 0.002), and the EDSS 4.0 milestone (HR = 0.56; 95% CI = 0.36-0.90; p = 0.015). Sensitivity analysis showed the bound of significance for unmeasured confounders. INTERPRETATION: Greater benefits on disability progression may be obtained by an early IFNbeta treatment in RRMS.

First hip arthroplasty register in Italy: 55,000 cases and 7 year follow-up.

The Register for Orthopaedic Prosthetic Implantation (RIPO) has been prospectively collecting data on hip prostheses performed in all the orthopaedic units in the region Emilia-Romagna since January 2000. The register aims to determine the characteristics of patients, evaluate the effectiveness of prostheses, and allow internal audit. Adherence to the register is compulsory (93% capture). By 31 December 2006 the register contained data on 35,041 primary total hip arthroplasty (THA), 14,613 hemiarthoplasties, and 5,878 revisions. All prosthetic components are registered on an individual basis. Survival analysis is done following the Kaplan Meier method. Cumulative survival rate at 7 years is 96.8% (95% CI: 96.4-97.1%) for THA and 97.6% (97.0-98.3%) for hemiarthroplasties. Multivariate analysis verified that survival of the THA is affected by pathology, where the worst conditions are rheumatoid arthritis, femoral neck fracture, and sequelae of coxitis or Paget's disease. Results are comparable to other major registers of Northern Europe and Australia.

Factors interfering with parenthood decision-making in an Italian sample of people with multiple sclerosis: an exploratory online survey.

BACKGROUND: Little is known about the influence of multiple sclerosis (MS) diagnosis on parenthood attitude in people with MS (pwMS). OBJECTIVE: To investigate the impact of diagnosis, clinical features and external disease-related influences on parenthood decision-making in Italian pwMS. METHODS: A web-based survey was posted on SMsocialnetwork.com to investigate clinical status, parenthood desire, influences on family planning, pregnancy outcomes, abortions and adoptions of pwMS. RESULTS: 33/395 respondents never wanted to become parent because of MS ("anti-parenthood after diagnosis"). 362 declared to be in favor of parenthood. 51% pwMS having a child by the survey time had already received the MS diagnosis at first childbirth. The frequency of a second child in pwMS after diagnosis was 38% compared to 67% in people without yet MS diagnosis. 16% of pwMS were discouraged to become parent after diagnosis, mainly by medical personnel. In 71% of respondents, diagnosis did not delay the decision to become parent and only 39% were counseled by treating physician to plan pregnancy. Patients' distribution according to the clinical phenotype (exclusively relapsing vs exclusively progressive) showed a higher proportion of progressive patients in the "anti-parenthood after diagnosis" subgroup. CONCLUSION: MS diagnosis impacted dramatically on the life project of 7% of pwMS that decided not to have children because of the disease and in pro-parenthood pwMS impacted especially on having the second child. Only a minority was counseled to plan pregnancy. A worse disease course driving to a progressive phenotype at survey time might have negatively impacted on parenthood desire.

Fertility concerns, preservation strategies and quality of life in young women with breast cancer: Baseline results from an ongoing prospective cohort study in selected European Centers.

OBJECTIVES: Most research addressing needs and concerns of young patients with breast cancer (≤40 years) is retrospective. The HOHO European protocol is a prospective multicenter cohort study of young women with newly diagnosed breast cancer, about fertility, psychosocial and quality of life concerns. Here we report the baseline data and focus on predictors of fertility concerns. MATERIALS AND METHODS: Patient surveys and medical record review were used. The baseline survey included sociodemographic, medical and treatment data as well as questions on fertility concerns and preservation strategies. Subscales from the CAncer Rehabilitation Evaluation System-Short Form (CARES-SF) were administered to measure specific quality of life aspects. Uni- and multivariable modeling were used to investigate predictors of greater fertility concern. RESULTS: Among 297 eligible respondents, 67% discussed fertility issues before starting therapy, 64% were concerned about becoming infertile after treatment, and 15% decided not to follow prescribed therapies. Fifty-four percent of women wished future children before diagnosis; of these, 71% still desired biologic children afterwards. In multivariable analysis, not having children was the only patient characteristic significantly associated with fertility concerns at diagnosis. Twenty-seven percent used fertility preservation strategies. Women who received chemotherapy reported greater physical (p = 0.021) and sexual difficulties (p = 0.039) than women who did not. Women who were married or had a partner reported less psychosocial problems than single women (p = 0.039). CONCLUSIONS: Young women with newly diagnosed breast cancer have several concerns, including, but not limited to, fertility. The HOHO European study provides valuable information to develop targeted interventions.

MRI activity and neutralising antibody as predictors of response to interferon beta treatment in multiple sclerosis.

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.

Recombinant interferon beta or glatiramer acetate for delaying conversion of the first demyelinating event to multiple sclerosis.

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.

Fake news, influencers and health-related professional participation on the Web: A pilot study on a social-network of people with Multiple Sclerosis.

BACKGROUND: Over the last few decades, patients have increasingly been searching for health information on the Internet. This aspect of information seeking is important, especially for people affected by chronic pathologies and require lifelong treatment and management. These people are usually very well informed about the disease but are nonetheless vulnerable to hopes of being cured or saved, often amplified by misinformation, myths, legends, and therapies that are not always scientifically proven. Many studies suggest that some individuals prefer to rely on the Internet as their main source of information, often hindering the patient-doctor relationship. A professional approach is imperative to maintain confidentiality, honesty, and trust in the medical profession. OBJECTIVE: we aimed to examine, in a medically supervised Italian web community (SMsocialnetwotk.com) dedicated to people with Multiple Sclerosis (pwMS), the posts shared by users and to verify the reliability of contents of posts shared by users pinpointed as Influencers through an online questionnaire. METHODS: we grouped the posts published on SMsocialnetwork from April to June 2015 into those with medical content (scientifically correct or fake news), and those related to social interactions. Later, we gave a questionnaire to the community asking to identify the three users/Influencers providing the most reliable advice for everyday life with MS and the three users/Influencers providing the most useful information about MS treatments. RESULTS: 308 posts reported scientific and relevant medical information, whereas 72 posts included pieces of fake news. 1420 posts were of general interest. Four out of the 6 Influencers had written only posts with correct medical information (3 were pwMS, 1 was a Neurologist) and never any fake news. The remaining 2 appointed Influencers (2 pwMS) had written only posts about general interests. CONCLUSION: the identification of fake news and their authors has shown that the latter are never appointed as Influencers. SMsocialnetwork.com acted as a "web safe environment" where the Influencers contributed by sharing only correct medical information and never fake news. We speculate that the presence of neurologists and psychologists supervising the information flow might have contributed to reduce the risk of fake news spreading and to avoid their acquisition of authoritative meaning.

Determination of crystallinity and crystal structure of Hylamer polyethylene after in vivo wear.

Hylamer polyethylene is a crystalline form of polyethylene of 70% crystallinity whereas conventional polyethylene (PE) has 50% crystallinity. Crystallinity is the percentage by weight of the crystalline phase present in the whole polymer, which comprises both amorphous and crystalline phases. Clinical experience has shown that Hylamer components used in joint prostheses, if sterilized by gamma rays in the presence of oxygen, are easily affected by wear, which leads to osteolysis. The authors have analyzed the crystallinity of polyethylene liners removed from seven patients who had received Hylamer polyethylene implants sterilized by gamma rays in air and had suffered prosthetic loosening, using Raman spectroscopy coupled with partial least squares (PLS) analysis. The results have been compared to those of two controls who had received Hylamer polyethylene implants sterilized by gamma irradiation in a nitrogen atmosphere. The crystal structure of wear particles released into the tissues from the Hylamer liners sterilized by gamma rays in air is also studied. The materials undergoing two different types of sterilization methods show different crystallinity values (71.50 vs. 69.43), but the crystallinity do not change according to wear (worn and unworn liner region). Both monoclinic and orthorhombic phases are present in the liner, while in wear debris prevalently monoclinic crystals are found in both types of sterilized liners. Different crystallinity rates can explain different wear rates observed in vivo.

Cisplatin and etoposide combination chemotherapy for locally advanced or metastatic thymoma. A phase II study of the European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group.

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.

Two schedules of teniposide with or without cisplatin in advanced non-small-cell lung cancer: a randomized study of the European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group.

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.

Treatment of brain metastases of small-cell lung cancer: comparing teniposide and teniposide with whole-brain radiotherapy--a phase III study of the European Organization for the Research and Treatment of Cancer Lung Cancer Cooperative Group.

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.

Pharmacokinetics of mitomycin C in pelvic stopflow infusion and hypoxic pelvic perfusion with and without hemofiltration: a pilot study of patients with recurrent unresectable rectal cancer.

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.

Combination chemotherapy with carboplatin and methotrexate in the treatment of advanced urothelial carcinoma. A phase II study.

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.

Preoperative concurrent radiation therapy and cisplatinum continuous infusion in IIIa (N2) non small cell lung cancer. A pilot study.

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.

Phase II trial of weekly 4-epi-doxorubicin (epirubicin) in squamous cell carcinoma of the head and neck.

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.

Antiemetic activity of oral lorazepam in addition to methylprednisolone and metoclopramide in the prophylactic treatment of vomiting induced by cisplatin. A double-blind, placebo-controlled study with crossover design.

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.