Cost-effectiveness analysis of interferon as adjuvant therapy in high-risk melanoma patients in Spain.

In the randomised clinical trial E1684, the administration of interferon (IFN) alpha-2b resulted in prolonged disease-free and overall survival in high-risk melanoma patients following surgical resection. However, and considering the cost and toxicity of IFN, the convenience of its widespread use should be evaluated. The aim of this study was to analyse the cost-effectiveness ratio of adjuvant therapy with IFN alpha-2b in melanoma patients versus an untreated control group. A Markov model was used to compare two hypothetical cohorts of 1000 patients aged 50 years, according to the clinical outcome of the E1684 study. The cohort of patients treated with IFN alpha-2b has an increased overall survival of 1.90 years during the patient's lifetime. The incremental discounted cost per life year gained of IFN versus observation is 9015 Euros according to the projection generated by the model. The sensitivity analysis demonstrated that changes in the most relevant study end-points do not modify the study outcome. In conclusion, in high-risk melanoma patients following surgical resection, the cost-effectiveness of IFN alpha-2b (at a dose of 20 MU/m2/day, 5 days per week for one month, followed by 10 MU/m2 TIW, up to one complete year of therapy) versus an untreated control group is within the limits established in health economics to determine if adoption of a new treatment is economically justified and is comparable with other interventions in which cost-effectiveness is acceptable to the National Health System.

Infectious complications in 126 patients treated with high-dose chemotherapy and autologous peripheral blood stem cell transplantation.

The effect of an extensive prophylactic antimicrobial regimen was prospectively assessed in 126 patients after high-dose chemotherapy and autologous PBSC. They received ciprofloxacin (500 mg/12 h), acyclovir (200 mg/6 h), and itraconazole (200 mg/12 h) orally until neutrophil recovery. Febrile patients received i.v. imipenem (500 mg/6 h) to which vancomycin and amikacin were added if fever persisted for 2-3 and 5 days, respectively. Amphotericin B lipid complex was further given on day 7 or 8 of fever. Median times for a neutrophil count of >0.5 x 10(9)/l and a platelet count of >20 x 10(9)/l were 9 and 11 days. Severe neutropenia (<0.1 x 10(9)/l) lasted for a median of 5 days in which 72% of febrile episodes and 50% of cases of bacteremia occurred. Gram-positive bacteria were isolated in 30 of 40 episodes of bacteremia, 25 of which were caused by Staphylococcus epidermidis. Clinical foci were the intravascular catheter in 35 cases, respiratory infection in 11, cellulitis in two, anal abscess in one, and neutropenic enterocolitis in one. The high incidence of febrile episodes (94%) and bacteremias (31%) may be due to the lack of efficacy of antimicrobial prophylaxis and the persistence of a 5-day period of severe neutropenia.

Prognostic value of HER-2/neu and p53 expression in node-positive breast cancer. HER-2/neu effect on adjuvant tamoxifen treatment.

HER-2/neu and p53 expression, conventional clinical and pathologic prognostic factors, were evaluated in a retrospective series of 283 node-positive breast cancer patients. Overexpression was determined by immunohistochemistry in formalin-fixed paraffin-embedded tissue blocks. Twenty one percent were HER-2/neu positive and 40% p53 positive. HER-2/neu expression was related to axillary lymph node metastasis (P=0.014), inflammatory infiltrates (P=0.004), and the absence of oestrogen (ER) (P=0.0026) and progesterone (P=0.01) receptors (PR). p53 expression was related to lymph node involvement (P=0.03), necrosis (P=0.036), absence of ER (P=0.028) and PR (P=0.065). p53 was not associated with outcome. HER-2/neu was an unfavourable prognostic factor for disease-free (DFS) (P=0.05) and overall survival (OS) (P=0.02) in univariate analysis. Multivariate analysis showed that the number of involved axillary nodes (P<0.00001), age (P=0.004), grade (P=0.04), and PR (P=0.04) were independent predictors for OS. ER-positive patients treated with adjuvant tamoxifen had shorter DFS and OS when they were HER-2/neu positive.

[Malignant pleural mesothelioma: clinical characteristics, prognostic factors and treatment]. / Mesotelioma maligno pleural. Características clínicas, factores pronósticos y tratamiento.

Malignant pleural mesothelioma soon leads to death no matter what type of treatment is provided. We discuss the clinical signs, prognostic factors and treatment given in 41 cases managed over the past 13 years in our oncology department. 32% had been exposed to asbestos, 61% were 60 years old or younger, 71% had a Karnofsky's index > or = 80% and 63% were stage I (Butchart). The first symptom leading to diagnosis was pain in 66% and mean time between first symptom and diagnosis was 3 months. Thirty patients never experienced full remission of disease: 15 were treated with palliative chemotherapy (CHT), 1 with palliative radiotherapy (RT), 5 with partial pleurectomy (PP) plus RT and/or CHT. Nine were given symptomatic treatment only. Only 11 (27%) patients experienced full remission after treatment: 7 had had extrapleural pneumonectomy, 2 had been given CHT and RT series and 4 had undergone PP with or without RT and/or CHT follow-up. Only 3 of these patients were still alive with no relapse more than 1 year later. Mean survival was 8 months. Univariate analysis revealed that the prognostic factors influencing survival were age and Karnofsky's index. Patients initially treated with surgery had a higher rate of survival. In conclusion, only Karnofsky's index and age were prognostic factors in our series. The better survival of patients initially treated surgically is probably related to prior screening.

[Lymphomas originating in the otorhinolaryngeal region: 10 years' experience]. / Linfomas originados en el área otorrinolaringológica: experiencia de 10 años.

BACKGROUND: Non-Hodgkin's lymphomas (NHL) originated in the otorhinolaryngological (ORL) area are rare diseases and its therapy is poorly established. METHODS: The diagnostic features, treatment and outcome based on therapy of 34 NHLs originated in the ORL area and seen in the Oncology Service from the Hospital de la Santa Creu i Sant Pau during a ten year period were reviewed. RESULTS: The predominant primary localization was the tonsil (17 patients), followed by rhinopharynx (8), massive involvement of Waldeyer's ring (4), and oropharynx, maxillary sinus and larynx in the remaining cases. In 26 patients the diagnosis was high-grade lymphoma. The stage distribution was 8 patients (24%) in stage I, 16 in stage II (47%), 3 in stage III (9%), and 5 in stage IV (16%). The treatment was heterogeneous and consisted in chemotherapy in 29 patients (38%), radiotherapy in 5 (15%) or the combination of both in 16 (47%). Eleven patients relapsed (38%), more commonly those treated with radiotherapy. The specific actuarial survival was 69%. CONCLUSIONS: NHL originated in the ORL area are uncommon neoplastic diseases, with a commonly dramatic response to chemotherapy. This should be the initial therapeutic modality in all cases.

[The modification of the toxicity produced by chemotherapy in testicular cancer by adapting its intensity to prognostic groups]. / Modificación de la toxicidad producida por la quimioterapia en el cáncer de testículo al adecuar su intensidad a los grupos pronósticos.

BACKGROUND: The reduction of iatrogenesis is fundamental in the treatment of germ-cell testicular tumors (GTT) because of the high incidence of cures achieved. On the other hand, the tumoral mass and the serum concentration of the beta fraction of the gonadotropin hormone (CGH) and of alphafetoprotein allow the differentiation of 2 clear prognostic groups; those for which the intensity of chemotherapy may be adapted to reduce its collateral effects and improve the results. METHODS: In the Oncology Department of the Hospital de la Santa Creu i Sant Pau 23 patients with GTT of good prognosis were treated between 1984-1990. These patients were given the combination of etoposide-cisplatin (EP) over the same period. Twenty patients with a bad prognosis received the alternative scheme of bleomycin-vincristine-methotrexate-cisplatin/etoposide-cisplatin- phosphamide (BOMP/EPI). RESULTS: In comparison to the classical treatment with cisplatin-vinblastine-bleomycin (PVB) the EP association demonstrated less iatrogenesis except in regards to the formation of granulocytopenia which was higher. The BOM/EPI combination conditioned greater hematological toxicity during the acute phase and the first observations suggested a diminution of chronic iatrogenesis. CONCLUSIONS: These results indicate that chemotherapy in testicular cancer may be adapted to the aggressiveness of the with the aim to thereby reduce global toxicity.

[10 Year follow up of chemotherapy and surgery on the second laparotomy in advanced ovarian cancer]. / Experiencia a 10 años con quimioterapia y cirugía en la segunda laparotomía en cáncer de ovario avanzado.

BACKGROUND: Advanced ovarian neoplasm has bad prognosis. There is little knowledge as to the effect of surgical and chemotherapy treatments on long-term survival. METHODS: Seventy-two patients with advanced epithelial ovary carcinoma (53 stage III and 19 stage IV) were treated according to a treatment regimen with reduction surgery, five cycles of chemotherapy with cyclophosphamide, adriamycin and cisplatin (CAP) followed by second revision laparotomy. RESULTS: The rate of response for the CAP schedule was 80%, of which 16 patients (23%) showed complete response (CR), 7 (10%) partial microscopic response (PMiR) and 33 (47%) partial macroscopic response (PMR). Complete resection of residual masses was performed on the second laparotomy in 14 of the 33 patients with parital response. The median survival for all the group was 36 months with overall actuarial survival of 27% at 10 years. The survival of the group of patients with CR was significantly longer than that of PMiR and other groups. Significant differences favorable for the group of partial response with second attempt radical surgery were found versus the group in which te second surgical resection was not radical. FIGO III stage and prechemotherapy tumor size less than 5 cm were found to have favorable effect in the rate of response and survival. CONCLUSIONS: The use of CAP chemotherapy achieved complete response in 23% of the patients studied. This group of patients showed to have a greater probability of longer survival. Second attempt surgery on the second laparotomy offers therapeutic benefits when radical.

[Identification of 2 families with hereditary nonpolyposis colonic cancer (HNPCC) and the Amsterdam criteria. Relevance of the genealogic tree and follow-up]. / Identificación de dos familias con cáncer de colon hereditario no polipósico (CCHNP) y criterios de Amsterdam. Relevancia del árbol genealógico y las medidas de seguimiento.

Hereditary nonpolyposis colorectal cancer (HNPCC) diagnosis is based either on the so-called "Amsterdam 1 criteria" or "Amsterdam 2 criteria", which includes extracolonic neoplasms associated with Lynch II syndrome. Many families are suspected of having a hereditary predisposition to cancer and may benefit from close surveillance. We describe a family (family 1) with suspected HNPCC at the beginning who fulfilled the Amsterdam 1 criteria over the course of its follow-up. We also describe an Amsterdam 2 family (family 2) with a very young affected individual. Both of them received genetic counseling and screening recommendations. A total colonoscopy was done to an asymptomatic member of family 1 and he was diagnosed with an early-stage colon cancer. He underwent subtotal colectomy because of the high risk of metachronous lesion. Screening recommendations must be the same in Amsterdam 2 families as in Amsterdam 1. Both families show the importance of considering the family history when hereditary criteria are suspected.

[A protocol for the treatment of cancers of the tongue]. / Protocole de traitement des cancers de la langue.

The protocole of multidisciplinary therapy of the tongue and base of the tongue tumors in the "Hospital de la Sta. Creu i Sant Pau" is presented. The exposition of the management trends by surgery, radiotherapy and chemotherapy, in our protocole, is followed by the review of the therapeutic indications with special enphasis in the topographic ones in order to plan the surgical treatment. The non advanced tumors will be as well treated by intersticial radiotherapy as by surgery. In the treatment of the advanced tumors the multidisciplinary managament results essential. Depending on the degree of invasion, the topography of the tumor and the outline of therapeutic trials, the therapy will be chosen.

The role of anxiety and adaptation to illness in the intensity of postchemotherapy nausea in cancer patients.

The aim of this work was to assess whether cancer patients presenting high anxiety levels or poor adaptation to cancer experience higher levels of postchemotherapy nausea, regardless of the emetogenicity of the chemotherapy schedule. Sixty-three patients were interviewed before receiving their chemotherapy schedule and some psychological variables were assessed. Nausea intensity was also assessed after treatment. The results showed that patients with relatively higher levels of nausea reported higher levels of anxiety prior to chemotherapy and lower levels of adaptation to cancer. Thus, evidence for a modulating effect of psychological factors in postchemotherapy emesis is suggested.

Chemotherapy (CAP) for the treatment of advanced ovarian cancer and second-effort surgery in the second look.

Seventy-two patients with advanced ovarian cancer received CAP chemotherapy followed by laparotomy and 'second-effort' surgery. The overall response to CAP therapy was 80%. A complete pathological response (CPR) was obtained in 16 patients and partial microscopic (PMiR) and macroscopic responses in 7 and 33 cases, respectively. The actuarial survival for the entire group was 36% at 50 months with a median survival of 34 months. No significant differences in survival between the CPR and PMiR groups were found. Radical second-effort surgery showed a somewhat beneficial effect. The tumor size before chemotherapy (less than 5 cm) and FIGO stage III had a significantly favorable effect on response rate and survival.

Fungal infections in patients with solid tumors treated with high-dose chemotherapy and autologous peripheral blood stem cell transplantation.

The incidence and risk factors for fungal infection were assessed in 291 patients who had solid tumors and were undergoing autologous peripheral blood stem cell transplantation. The first 162 patients received prophylactic itraconazole, and 129 patients received nystatin. Empiric amphotericin B was given at day 7 of febrile neutropenia. Fungal infections developed in 52 patients: 47 (16%) were superficial and 6 (2%) were systemic. Itraconazole prophylaxis and only a few days of febrile neutropenia were independently associated with a decrease in the incidence of superficial infections. Only two patients required empiric amphotericin B. Systemic antifungal prophylaxis does not seem to be justified for patients with solid tumors and autologous peripheral blood stem cell transplantation. Empiric amphotericin B may be safely started at day 7 of febrile neutropenia.

Aggressive natural killer cell leukaemia/lymphoma in two patients with lethal midline granuloma.

We report two patients with leukaemic proliferations of large granular lymphocytes. The immunophenotype study showed that the leukaemic cells were positive for CD2, CD38, CD56 and anti-HLA-DR monoclonal antibodies and negative for other T-cell (CD3, CD4, CD8) and B-cell markers (CD19, CD20 and surface immunoglobulins). The clinical course was acute and a diagnosis of aggressive natural killer cell leukaemia/lymphoma was made. No clonal rearrangements of either C beta T-cell receptor or JH immunoglobulin genes were found. Functional studies done in one patient demonstrated non-restricted cytotoxic activity after activation with IL-2. Lethal midline granuloma had been previously diagnosed in both patients. A possible relationship between this entity and the natural killer cell leukaemia is discussed.

Bone Marrow Transplantation: Prognostic Factors of Peripheral Blood Stem Cell Mobilization with Cyclophosphamide and Filgrastim (r-metHuG-CSF): The CD34+ Cell Dose Positively Affects the Time to Hematopoietic Recovery and Supportive Requirements after High-Dose Chemotherapy.

To prospectively analyze factors that influence peripheral blood stem cell (PBSC) collection and hematopoietic recovery after high-dose chemotherapy (HDC), 39 patients received cyclophosphamide 4 g/m(2) and rHuG-CSF (Filgrastim) 5 &mgr;g/kg/day. Leukapheresis was started when CD34(+) cells/mL were > 5 x 10(3). A minimum of 2 x 10(6) CD34(+) cells/kg was collected. Median steady-state bone marrow CD34(+) cell percentage was 0.8% (range, 0.1 to 6). Thirty-two patients received HDC with autologous PBSC transplantation plus Filgrastim. A median of 2 (range, 0 to 6) leukapheresis per patient were performed and a median of 6.3 x 10(6) CD34(+) cells/kg (range, 0 to 44.4) collected; four patients failed to mobilize CD34(+) cells. The number of cycles of prior chemotherapy had an inverse correlation with the number CD34(+) cells/kg collected (r = -0.38; p < 0.005). Patients with <7 cycles had a higher predictability for onset of leukapheresis than patients with (3) 7 (93% versus 50%; p < 0.005). The four patients who failed to mobilize had received >/=7 cycles. The number of CD34(+) cells/kg infused after HDC had an inverse correlation with days to recovery to 0.5 x 10(9) neutrophils/L and 20 x 10(9) platelets/L (r = -0.68 and -0.56; p < 0.005). The effect of these factors on mobilization and hematopoietic recovery were confirmed by multivariate analysis. Requirements for supportive measures were significantly lower in patients given a higher dose of CD34(+) cells/kg. Therefore, PBSC collection should be planned early in the course of chemotherapy. Larger number of CD34(+) cells/kg determined a more rapid hematopoietic recovery and a decrease of required supportive measures.