Tolerability of acute migraine medications: influence of methods of assessment and relationship with headache attributes.

Tolerability is an important attribute of patient satisfaction with, and consequence adherence to, migraine acute treatment. Nevertheless, the determinants of tolerability are poorly explored. Accordingly, our objectives were: (i) in subjects receiving triptans, to contrast two methods of assessing adverse events (AEs); and (ii) to explore the relationship between migraine features and treatment attributes with tolerability. We surveyed 365 migraineurs who had been using the same triptan for at least 3 months. After prospectively treating an attack, headache characteristics and treatment response were assessed using headache calendars. Subjects also completed a standardized questionnaire, first asking about any AE and then prompting patients with a list of possible AEs. We contrasted both sets of answers and conducted logistic regression to assess if headache attributes or response to therapy influenced tolerability. Using the unprompted method, AEs occurred in 11.5-36.4% of patients, depending on the triptan used. Using the prompted method, they ranged from 26.9 to 64.3%. Chest and neck tightness were spontaneously reported by 3.5% of the sample, vs. 7.4% when prompted (P < 0.05). Chest pain was not spontaneously reported and was elicited in nine patients (2.5%, P = 0.002). Feeling groggy occurred in 5.7 and 17.5% (P < 0.001). AEs were not a function of headache severity, disability, efficacy of the drug, time to meaningful relief with the drug or recurrence of pain. The report of AEs varies dramatically with the methods of assessment. However, tolerability is not influenced by the severity of the attacks or by medication efficacy.

Merkel cell carcinoma: experience of 14 cases and literature review.

Merkel cell carcinoma is an aggressive skin cancer, with a significant incidence of locoregional lymphnode involvement, which requires timely diagnosis, adequate staging and aggressive therapy based essentially on surgical procedures. The aim of this study is to report our experience and to compare our results with literature findings, in order to discuss the role of the procedures adopted and their influence on prognosis. From July 1995 to April 2005, 14 patients were treated and followed-up for MCC in the National Cancer Institute of Naples. Tumor location was: buttocks (43%), extremities (36%) head (7%), unknown (14%). There were 7 Stage I, 5 Stage II and 2 Stage III patients. Surgical treatment consisted in wide excision (WE) in Stage I cases, WE and regional lymphadenectomy followed by radio- or chemo-therapy in Stage II and combined surgical and pre- and post-operative medical treatments in Stage III. Overall disease specific survival rate was 64% (median follow up 44 months). Recurrence occurred in 86% of Stage I and 20% of Stage II patients and involved, in 83.3% of Stage I patients, the lymph nodal draining basin. The treatment of recurrence implied surgery and radio or radiochemotherapy. Overall survival rate of recurrent patients was 57% (median follow-up 37.2 months). Due to the particular lymphotrophism of MCC, major care should be set on investigation and treatment of tumor lymph nodal draining basin. As long as the disease remains surgically manageable the prognosis for patients with MCC is favourable. The role of radio and chemotherapy is not yet assessed.

[Clinical guidelines for the management of gastrointestinal stromal tumors]. / Raccomandazioni cliniche per la diagnosi, la terapia ed il follow-up dei tumori stromali gastrointestinali.

Treatment of gastrointestinal stromal tumors (GIST) has been revolutioned by the recently discovered molecular mechanism responsible for the oncogenesis of this disease. In addition, due to the rapid progress at molecular and clinical level observed in the last few years, there is a need to review the current state of the art in order to delineate appropriate guidelines for the optimal management of these tumors. A panel of experts from several specialities, including medical oncology, surgery, pathology, molecular biology and imaging, were invited to participate in a meeting to present and discuss a number of pre-selected questions, and to achieve a consensus according to the categories of the National Comprehensive Cancer Network (NCCN) and the Standard Options Recommandations (SOR) of the French Federation of Cancer Centers. Generally, consensus points were from categories 2A of the NCCN and B2 of the SOR. Conventional histologic examination with immunohistochemistry for CD117, CD34, SMA, S-100 and desmin is considered standard. Molecular analysis for the identification of KIT and PDGFRA mutation may be indicated in CD117-negative GIST. Complete tumor resection with negative margins is the optimal surgical treatment. Adjuvant imatinib should be considered an experimental approach. Neoadjuvant imatinib is also experimental, although its use may be justified in unresectable or marginally resectable GIST. Imatinib should be started in metastatic or recurrent disease, and should be continued until progressive disease or drug intolerance. In these cases, sunitinib can be used. The optimal criteria for the assessment and monitoring of GIST undergoing imatinib therapy are not well known, but they should include reduction in tumor size and disease stabilization, as well as reduction of tumor density on CT scan and metabolic activity on PET scan.

Expression of CD40 has no predictive value in soft tissue sarcomas.

BACKGROUND: CD40, a member of the tumor necrosis factor receptor superfamily, is capable of mediating the induction of apoptosis in tumors including sarcomas. The expression of proapoptotic receptor contribute to the induction of apoptosis by chemotherapeutic drugs. The present study was undertaken to determine if there is a correlation between the expression of CD40 in spindle-cell sarcomas and the response to epirubicin and ifosfamide chemotherapy. PATIENTS AND METHODS: Immunohistochemical analysis of CD40 expression was performed on 59 paraffin-embedded archival tissues. Evaluation of objective tumor response was carried out according to the WHO criteria. Correlations with response to chemotherapy and baseline patients' characteristics were investigated using Chi-square tests. RESULTS: Positive CD40 staining was observed in 42 tumors; it was expressed in < 10% of cells in 14 (24%), in 10 to 50% in 16 (27%) and in more than 50% of cells in 12 (20%) tumors. No significant association was found between CD40 expression, response to chemotherapy and other clinical and pathological characteristics. CONCLUSION: CD40 expression in spindle-cell soft tissue sarcomas is not associated with response to ifosfamide plus epirubicin chemotherapy.

Neoadjuvant chemotherapy for intermediate/high-grade soft tissue sarcomas: five-year results with epirubicin and ifosfamide.

BACKGROUND: Neoadjuvant chemotherapy for intermediate/high-grade soft tissue sarcomas (STS) may provide some advantages for facilitating the surgical resection of the tumor and for disease control. However its role as induction therapy before surgery should still be proved. PATIENTS AND METHODS: Twenty-one patients with intermediate/high-grade STS and tumor size > or = 5 cm were consecutively treated from 1997 to 2001 with neoadjuvant chemotherapy based on epirubicin 60 mg/m2/day on days 1 and 2 and ifosfamide 1.8 gr/m2/day on days 1 through 5 every three weeks. Evaluation of objective tumor response and toxicity were carried out according to WHO criteria. RESULTS: Nine partial responses were documented; stable disease in 11 patients, progressive disease in one patient. Apart from nine cases of grade 4 neutropenia, the treatment was generally well-tolerated. Twelve patients underwent conservative and limb salvage surgery. CONCLUSION: This therapeutic approach seems to be effective in facilitating surgery. Neutropenia was the most significant toxicity but it was preventable or medically treatable with G-CSF support.

Adjuvant chemotherapy for adult soft tissue sarcomas of the extremities and girdles: results of the Italian randomized cooperative trial.

PURPOSE: Adjuvant chemotherapy for soft tissue sarcoma is controversial because previous trials reported conflicting results. The present study was designed with restricted selection criteria and high dose-intensities of the two most active chemotherapeutic agents. PATIENTS AND METHODS: Patients between 18 and 65 years of age with grade 3 to 4 spindle-cell sarcomas (primary diameter > or = 5 cm or any size recurrent tumor) in extremities or girdles were eligible. Stratification was by primary versus recurrent tumors and by tumor diameter greater than or equal to 10 cm versus less than 10 cm. One hundred four patients were randomized, 51 to the control group and 53 to the treatment group (five cycles of 4'-epidoxorubicin 60 mg/m(2) days 1 and 2 and ifosfamide 1.8 g/m(2) days 1 through 5, with hydration, mesna, and granulocyte colony-stimulating factor). RESULTS: After a median follow-up of 59 months, 60 patients had relapsed and 48 died (28 and 20 in the treatment arm and 32 and 28 in the control arm, respectively). The median disease-free survival (DFS) was 48 months in the treatment group and 16 months in the control group (P =.04); and the median overall survival (OS) was 75 months for treated and 46 months for untreated patients (P =.03). For OS, the absolute benefit deriving from chemotherapy was 13% at 2 years and increased to 19% at 4 years (P =.04). CONCLUSION: Intensified adjuvant chemotherapy had a positive impact on the DFS and OS of patients with high-risk extremity soft tissue sarcomas at a median follow-up of 59 months. Therefore, our data favor an intensified treatment in similar cases. Although cure is still difficult to achieve, a significant delay in death is worthwhile, also considering the short duration of treatment and the absence of toxic deaths.

Leiomyosarcoma of the Oropharynx and Neurogenic Tumors in a Young Patient With Turner's Syndrome.

PATIENT: A case of Turner's syndrome developing a leiomyosarcoma of the oropharynx and metachronous neurogenic tumors (mediastinal 'ganglioneuroblastoma intermixed', subcutaneous neurilemoma) is described. DISCUSSION: To our knowledge, this case is the second reported leiomyosarcoma in a patient with Turner's syndrome. Also the site of involvement (palate and oropharynx) is particularly unusual for the already rare leiomyosarcomas in the young age.

Lack of Activity of Docetaxel in Soft Tissue Sarcomas: Results of a Phase II Study of the Italian Group on Rare Tumors.

Purpose. The prognosis of advanced soft tissue sarcoma is poor, only a few drugs showing some activity with response rates around 15- 25%. Consequently drug development seems mandatory to improve treatment outcome. Following previous favourable EORTC experience, the Italian Group on Rare Tumors started a phase II study with docetaxel to confirm the activity of this drug in soft tissue sarcoma.Patients and methods. Thirty-seven patients with soft tissue sarcoma resistant to at least one anthracyclinecontaining regimen were enrolled in a phase II multicenter study evaluating docetaxel 100 mg/m(2) in a 1-h i.v. infusion q(3) weeks.Results.Thirty-seven patients were enrolled onto this phase II study and 36 were evaluable for response. Only one partial remission was observed [2.8% with 95% confidence interval (CI) 0.1- 16.2%]. Median progression-free and overall survival were 42 and 350 days, respectively. Neutropenia and leukopenia as well as cutaneous manifestations were the most common toxicities.Discussion. The results of this phase II study do not confirm a previous EORTC repor t on the activity of docetaxel in soft tissue sarcoma, but are consistent with other more recent phase II studies. The accumulated evidence does not justify the use of this drug in the management of patients suffering from this disease, resistant to anthracyclinecontaining regimens.

Multicentric giant cell tumor with viral-like inclusions associated with Paget's disease of bone: a case treated by steroid therapy.

We report a case of giant cell tumor of bone (GCTB) associated with Paget's disease unsuccefully treated with radiotherapy for some years but dramatically reduced in size with high dose of dexamethasone within few days. An ultrastructural study showed intranuclear virus-like inclusions in the multinucleated giant cells. The patient was then switched to prednisone plus diclofenac and he is still in almost complete remission after two years. The patient was from Avellino area, a small town in Southern Italy.

[Bacterial infections in cancer patients without neutropenia. Comparison between 2 antibiotic combinations (aztreonam and oxacillin versus cefoxitin and tobramycin)]. / Infezioni batteriche in pazienti neoplastici non neutropenici. Confronto tra due associazioni di antibiotici (aztreonam + oxacillina versus cefoxitina + tobramicina).

In the treatment of infections arisen in neoplastic patients without neutropenia, 2 antibiotic combinations (aztreonam + oxacillin vs tobramycin + cefoxitin), have been compared with regard to therapeutic effectiveness and tolerability. Twenty patients (age: 30-75) have been studied. Tolerability of both combinations was excellent. Results of this study showed a lower percentage of superinfections and a higher percentage of cure in patients treated with the combination aztreonam + oxacillin, even if the data were not statistically significant.

Combination chemotherapy (CVP or CHOP)- radiotherapy approach in early stage non-Hodgkins's lymphomas.

From January 1978 to December 1980, 42 patients with early stage non-Hodgkin's lymphoma other than of the gastrointestinal tract were treated with radiotherapy and combination chemotherapy. Eighteen patients in stage I were submitted to locally extended-field radiotherapy up to a mean dose of 48 Gy with a Co60 source and, after a 3-week rest period, to 6 cycles of combination chemotherapy. Twenty-four patients in stage II received 3 cycles of combination chemotherapy before and after irradiation, the same as for stage I. Combination chemotherapy consisted of cyclophosphamide, vincristine and prednisone (CVP) for 15 cases with favorable histology (3 NWDL, 1 NPDI, 11 DWDL), whereas it included cyclophosphamide, adriamycin, vincristine and prednisone (CHOP) for 27 cases with unfavorable histology (20 DPDL, 3 DM, 4 DH). Complete remission (CR) was achieved in 35/42 (83%) patients, with a highly significant difference between stage I (100%) and stage II (71%). After 42 months of follow-up, the probability of survival for all patients was 72%. Survival was better for stage I (88%) than for stage II (68%) and for favorable histology (87%) as compared to unfavorable histology (70%). Furthermore, survival was highly influenced by response to therapy. Indeed, actuarial survival rate for CR was 91% as compared to a median survival time of 10.2 months for the remaining patients. Four patients, all with poor histology, relapsed after 5-24 (mean 11) months of CR. Only one of them had an extension in extranodal sites and eventually died, despite the salvage treatment utilized. In our experience, locally extended-field irradiation combined with chemotherapy gave a high proportion of CR and seemed to prevent relapses, particularly in extranodal site.

Adenosine deaminase and purine nucleoside phosphorylase activities in peripheral lymphocytes from patients with solid tumours.

Adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) levels of peripheral blood mononuclear cells were measured in 34 patients with various types of solid tumours. The mean ADA activity was found to be significantly lower than in controls (P less than 0.005). Patients with nonresectable tumour or with recurrence after radical surgery showed low ADA levels, while patients operated upon and without recurrence had enzymatic activity not different from that of normal controls. The mean value of PNP activity was similar to that of normal controls; no differences were observed between operated patients without recurrence and cases with nonresectable tumour or with recurrence after surgical treatment. No effects on ADA and PNP levels appeared to be induced by chemotherapy.

Decreased adenosine deaminase activity in peripheral lymphocytes from tumor patients with metastasis.

We determined the levels of adenosine deaminase (ADA) activity in peripheral lymphocytes of 22 tumor patients: 54% had metastasis; 59% were undergoing chemotherapy at the time of the study. The mean ADA value of all patients was significantly lower than that of 15 healthy subjects of a similar age. When the patients were allocated by treatment and metastasis, the decrease of ADA activity appeared to be associated to the presence of metastasis.