Lifestyle improvement reduces the consumption of ultra-processed foods in adults with metabolic syndrome.

BACKGROUND AND AIMS: The high consumption of ultra-processed products is a concern because it is positively associated with the incidence of chronic non-communicable diseases, as metabolic syndrome (MetS). The aim is to evaluate the effects of three different interventions to modify lifestyle on the consumption of ultra-processed foods in adults with MetS. METHODS AND RESULTS: This was a randomized clinical trial, in which the participants were divided into three groups: Standard Intervention (SI), Group Intervention (GI) and Individual Intervention (II). The interventions were carried out over a three-month period and the data was collected in a 24-h food record, taken at the beginning and end of the intervention. The food they ate was classified into four groups according to the degree of processing (unprocessed or minimally processed foods, processed culinary ingredients, processed foods, and ultra-processed foods) in accordance with the NOVA food classification. Seventy adults took part in the study with a mean age of 51.2 ± 6.6 years old; most of whom were female (55.7%). The amount of ultra-processed food consumed by the three groups (SI, GI and II) was significantly reduced (46%, 34%, and 33%, respectively). The amount of processed food consumed only reduced in the II group. The Total Energy Value (TEV) consumed by the SI and II groups decreased. CONCLUSIONS: The interventions that were intended to alter lifestyles were able to reduce the amount of ultra-processed food consumed, which can have an impact on the prevention and treatment of MetS. REGISTRATION: registered in the Brazilian Registry of Clinical Trials, ReBEC, under number: RBR-9wz5fc.

Nine weeks versus 1 year adjuvant trastuzumab in combination with chemotherapy: final results of the phase III randomized Short-HER study‡.

Background: Chemotherapy plus 1-year trastuzumab is the standard adjuvant treatment of HER2-positive breast cancer. The efficacy of less extended trastuzumab exposure is under investigation. The short-HER study was aimed to assess the non-inferiority of 9 weeks versus 1 year of adjuvant trastuzumab combined with chemotherapy. Patients and methods: HER2-positive breast cancer patients with node-positive or, if node negative, with at least one risk factor (pT>2 cm, G3, lympho-vascular invasion, Ki-67 > 20%, age ≤35 years, or hormone receptor negativity) were randomly assigned to receive sequential anthracycline-taxane combinations plus 1-year trastuzumab (arm A, long) or plus 9 weeks trastuzumab (arm B, short). This study was designed as a non-inferiority trial with disease-free survival (DFS) as primary end point. A DFS hazard ratio (HR) <1.29 was chosen as the non-inferiority margin. Analyses according to the frequentist and Bayesian approach were planned. Secondary end points included 2-year failure rate and cardiac safety. Results: A total of 1254 patients from 82 centers were randomized (arm A, long: n = 627; arm B, short: n = 626). Five-year DFS is 88% in the long and 85% in the short arm. The HR is 1.13 (90% CI 0.89-1.42), with the upper limit of the CI crossing the non-inferiority margin. According to the Bayesian analysis, the probability that the short arm is non-inferior to the long one is 80%. The 5-year overall survival (OS) is 95.2% in the long and 95.0% in the short arm (HR 1.07, 90% CI 0.74-1.56). Cardiac events are significantly lower in the short arm (risk-ratio 0.33, 95% CI 0.22-0.50, P < 0.0001). Conclusions: This study failed to show the non-inferiority of a shorter trastuzumab administration. One-year trastuzumab remains the standard. However, a 9-week administration decreases the risk of severe cardiac toxicity and can be an option for patients with cardiac events during treatment and for those with a low risk of relapse. Trial Registration: EUDRACT number: 2007-004326-25; NCI ClinicalTrials.gov number: NCT00629278.

[Iron intake and HFE gen in male adults from Buenos Aires]. / Ingesta de hierro y gen HFE en varones adultos de Buenos Aires.

Excess iron (Fe) intake in subjects carrying certain mutations in the HFE gene may result in Fe overload. To estimate risk of Fe overload, 166 male blood donors (19-65 years) from Buenos Aires city were investigated. Daily Fe intake (FeI), hem Fe intake, and Fe intake from SO4Fe enriched flours were estimated (SARA Computer Program and Food Composition Table, USDA). Serum ferritin and transferrin saturation were determined; criteria for Fe overload was serum ferritin > 300 ng/ml and transferrin saturation = 50%. HFE genotypes C282Y, H63D and S65C were analyzed by PCR-RFLP in blood samples. No participant presented FeI lower than the estimated average requirement (6 mg Fe/day) and 3.0% was over the upper level (45 mg Fe/day). Hem Fe and Fe from flour enrichment were 9.4% and 47.7% of daily Fe intake, respectively. A significant association was observed between the increase in serum ferritin (ng/ml) and the increase in FeI (p = 0.0472); 2.3% of the donors presented serum ferritin > 300 ng/ml and transferrin saturation = 50%. Genotypes associated with hereditary hemochromatosis (H63D, S65C and C282Y) were found in 29.3% of the donors. The percentage of transferrin saturation was higher in subjects carrying mutation than in wild type subjects (p = 0.0167). Although penetrance of hereditary hemochromatosis in the studied group was only 1.2%, an excessive Fe intake could enhance adverse effects in individuals unaware of any family history of Fe overload.

A simple and reproducible prognostic index in luminal ER-positive breast cancers.

BACKGROUND: The group of estrogen receptor (ER)-positive breast cancers (both luminal-A and -B) behaves differently from the ER-negative group. At least in early follow-up, ER expression influences positively patients' prognosis. This low aggressive biology flattens out the differences of clinical management. Thus we aimed to produce a prognostic index specific for ER-positive (ERPI) cancers that could be of aid for clinical decision. PATIENTS AND METHODS: The test set comprised 495 consecutive ER-positive breast cancers. Tumor size, number of metastatic lymph nodes and androgen receptor expression were the only independent variables related to disease-specific survival. These variables were used to create the ERPI, which was applied to the entire test set and to selected subpopulations (grade 2 (G2)-tumors, luminal-A and -B breast cancers). A series of 581 ER-positive breast cancers, collected from another hospital, was used to validate ERPI. RESULTS: In the test population, 96.9% of patients classified as ERPI-good showed a good prognosis compared with 79.6% classified as ERPI-poor (P < 0.001). ERPI effectively discriminated outcome in luminal-A and luminal-B and in G2-tumors. In the validation series, the ERPI maintained its value. CONCLUSION: ERPI is a practical tool in refining the prediction of outcome of patients with ER-positive breast cancer.

Impact of dental care in the prevention of bisphosphonate-associated osteonecrosis of the jaw: a single-center clinical experience.

BACKGROUND: Osteonecrosis of the jaw (ONJ) is associated with bisphosphonate (BP) therapy and invasive dental care. An Interdisciplinary Care Group (ICG) was created to evaluate dental risk factors and the efficacy of a preventive restorative dental care in the reduction of ONJ risk. PATIENTS AND METHODS: This prospective single-center study included patients with bone metastases from solid tumors. Patients who received at least one BP infusion between October 2005 and 31 August 2009 underwent one or more ICG evaluation and regular dental examinations. We also retrospectively evaluated patients with bone metastases from solid tumors who did not undergo dental preventive measures. RESULTS: Of 269 patients, 211 had received at least one infusion of BP therapy: 62% were BP naive and 38% had previous BP exposure. Of these 211 patients followed for 47 months, 6 patients developed ONJ (2.8%). Of 200 patients included in the retrospective analysis, 11 patients developed ONJ (5.5%). CONCLUSIONS: In comparison with published ONJ rates and those extrapolated from the retrospective analysis, the observed ONJ rate in the prospective group was lower, suggesting that implementation of a preventive dental program may reduce the risk of ONJ in metastatic patients treated with i.v. BP therapy.

Ventilatory muscle strength in cystic fibrosis patients: a literature review.

UNLABELLED: The ventilatory mechanic changes that occur in cystic fibrosis (CF) patients may lead to alterations in the respiratory muscle strength levels. However, the findings regarding the strength profile in these patients are still contradictory. OBJECTIVE: To evaluate, trough a literature review, the respiratory muscle strength behavior in CF patients. We have performed a search in Medline/Pubmed, Scielo, IBECS and LILACS databases selecting observational cross-sectional, prospective or retrospective studies, as well as randomized clinical trials, published between 1981 and 2011, using the following terms: cystic fibrosis, respiratory muscle strength, inspiratory maximal pressure and muscle training. The majority of the studies 71.24% have shown normal or above normal respiratory muscle strength, whilst 28.57% demonstrated reduced or near-normal values. Most of these findings were attributed to an increased work of breathing as a result of airway obstruction and chronic persistent cough. Taken together, the analyses of selected studies have showed conflicting findings regarding respiratory muscle strength behavior in these patients. However, most of the studies seem to indicate that CF patients presented maximum respiratory pressures normal or above predicted values.

Vascular endothelial growth factor genetic polymorphisms and haplotypes in female patients with bisphosphonate-related osteonecrosis of the jaws.

OBJECTIVE: To investigate the polymorphisms of the vascular endothelial growth factor (VEGF) gene in relation to female patients who developed bisphosphonate-related osteonecrosis of the jaws (BRONJ). METHODS: Test subjects were 30 Italian female patients with BRONJ (Group A). Control subjects were 30 female patients with a history of intravenous bisphosphonate use without any evidence of osteonecrosis (Group B) and 125 unrelated healthy volunteers (Group C). Three single-nucleotide polymorphisms were investigated: -634 G>C, occurring in 5' untranslated region (UTR); +936 C>T, occurring in 3' UTR; and -2578 C>A of the promoter region. RESULTS: The frequency of the VEGF CAC (+936/-2578/-634) haplotype was increased in patients with BRONJ, compared with female disease-negative controls [odds ratio (OR) = 2.76, 95% CI = 1.09-4.94, P = 0.039; corrected P value: P(c) = 0.117], and was also increased compared with female healthy controls (OR = 2.11, 95% CI = 1.14-3.89, P = 0.024; corrected P value: P(c) = 0.072). The CC homozygotes of -634G>C of VEGF gene and AA homozygotes of -2578C>A have also been significantly correlated in female patients who developed BRONJ compared with healthy controls (OR = 2.04, 95% CI = 1.12-3.70, P = 0.008; corrected P value: P(c) = 0.024). CONCLUSIONS: These results suggest a possible haplotype effect of VEGF polymorphisms expression in BRONJ Italian female patients. Studies with different and larger populations possibly using TagSNP to represent all haplotypes within the VEGF gene are needed to further delineate the genetic contribution of this gene to BRONJ.

Biology, prognosis and response to therapy of breast carcinomas according to HER2 score.

BACKGROUND: The standardization of the HER2 score and recent changes in therapeutic modalities points to the need for a reevaluation of the role of HER2 in recently diagnosed breast carcinoma. PATIENTS AND METHODS: A multicenter, retrospective study of 1794 primary breast carcinomas diagnosed in Italy in 2000/2001 and scored in HER2 four categories according to immunohistochemistry was conducted. RESULTS: Ductal histotype, vascular invasion, grade, MIB1 positivity, estrogen and progesterone receptor expression differed significantly in HER2 3+ tumors compared with the other categories. HER2 2+ tumors almost showed values intermediate between those of the negative and the 3+ subgroups. The characteristics of HER2 1+ tumors were found to be in between those of HER2 0 and 2+ tumors. With a median follow-up of 54 months, HER2 3+ status was associated with higher relapse rates in node-positive and node-negative subgroups, while HER2 2+ only in node positive. Analysis of relapses according to type of therapy provided evidence of responsiveness of HER2-positive tumors to chemotherapy, especially taxanes. CONCLUSIONS: The present prognostic significance of HER2 is correlated to receptor expression level and points to the need to consider HER2 2+ and HER2 3+ tumors as distinct diseases with different outcomes and specific features.

Effects of the use of respiratory physiotherapy in children admitted with acute viral bronchiolitis.

OBJECTIVE: To evaluate the effects of the use of respiratory physiotherapy in children admitted with acute viral bronchiolitis (AVB). METHODS: A literature review was done searching the Pubmed, LILACS, PEDro, and Scielo databases. The following key words were used: bronchiolitis, physiotherapy, techniques, physical therapy, and chest physiotherapy. Both controlled and uncontrolled clinical trials, without limits as to date, were selected. RESULTS: Fifteen articles were included and the use of different techniques of respiratory physiotherapy showed positive results in eight studies. Most (11) were controlled clinical trials, and only two had a double-blind design. Of the 14 studies with a control group, in six this group was submitted to nasopharyngeal aspiration. The most widely used techniques were manual vibration and postural drainage (eight studies), and then tapping/percussion (seven studied). The maneuvers considered as current, e.g., prolonged slow expiration, expiratory flow acceleration, and rhinopharyngeal retrograde clearance, were used in four, four, and two studies, respectively. CONCLUSIONS: The use of respiratory physiotherapy in children with AVB remains controversial. The heterogeneity of techniques evaluated in the studies limits the interpretation of efficacy, although its use was considered safe. Recent findings indicating a reduction in the length of the hospital stay remain to be confirmed.

Patients with advanced stage breast carcinoma immunoreactive to biotinylated Herceptin are most likely to benefit from trastuzumab-based therapy: an hypothesis-generating study.

BACKGROUND: Biotin-labeled trastuzumab (BiotHER) can be used to test for HER2 by immunohistochemistry. We previously showed that BiotHER immunoreactivity is highly correlated with HER2 amplification and indicated that it could be associated with better clinical outcome in advanced breast cancer patients receiving trastuzumab. PATIENTS AND METHODS: Tumor specimens and clinical information from 234 patients who received trastuzumab-based treatments were collected from 10 institutions. HER2 amplification and BiotHER immunoreactivity were assessed centrally. The effect of BiotHER positivity on response rate (RR), time to progression and survival were studied by univariate and multivariate analysis in patients presenting HER2-amplified breast cancer. The pathologic reviews of the assays were blinded to patient outcomes. RESULTS: BiotHER was positive in 109/194 (56%) HER2-amplified breast cancers and in one not amplified tumor. RRs were 74% [95% (confidence interval) CI 64%-81%] and 47% (95% CI 36%-58%) in BiotHER-positive and -negative tumors, respectively (P < 0.001). BiotHER immunoreactivity was independently associated with increased probability of tumor response (odds ratio 3.848; 95% CI 1.952-7.582), with reduced risk of disease progression [hazard ratio (HR) 0.438; 95% CI 0.303-0.633] and with reduced risk of death (HR 0.566; 95% CI 0.368-0.870) by multivariate analysis. CONCLUSION: The results support a role for BiotHER testing in better tailoring trastuzumab-based treatments in patients with advanced HER2-amplified breast cancers.

Teniposide in the treatment of small-cell lung cancer: the influence of prior chemotherapy.

Fifty patients with small-cell lung cancer (SCLC) were treated with teniposide (VM26) at 120 to 140 mg/m2 on days 1, 3, and 5, every 3 weeks. Twelve elderly patients were administered VM26 as first-line chemotherapy. Toxicity was manageable, myelosuppression being the major side effect. The response rate for 44 evaluable patients was 34% (36% for untreated patients); the median durations of response and survival were 230 and 208 days, respectively. Effectiveness of prior chemotherapy and time from last administration was found to influence patient response to VM26: 42% of responders to prior chemotherapy responded to VM26, while 0% of the nonresponders to prior chemotherapy responded to the new agent. Moreover, among patients pretreated with chemotherapy, 12% of those recently treated (earlier chemotherapy ending less than or equal to 2.6 months before administration of VM26) responded to VM26, while 53% of patients treated greater than 2.6 months earlier responded to VM26. Survival was influenced by common prognostic factors (performance status, weight loss, prior chemotherapy exposure). Selection of pretreated patients by type of exposure to prior chemotherapy may help in the testing of new drugs in this disease.

Phase II study of vinorelbine with protracted fluorouracil infusion as a second- or third-line approach for advanced breast cancer patients previously treated with anthracyclines.

PURPOSE: To evaluate the feasibility and activity of vinorelbine in association with protracted infusional fluorouracil in patients with advanced breast cancer who were previously treated with anthracycline-containing regimens. PATIENTS AND METHODS: Eighty-three consecutive patients were entered onto the study. Forty-three patients experienced treatment failure or relapse after anthracycline-based, first-line chemotherapy for advanced disease and 29 experienced treatment failure or relapse after first- and second-line approaches; 11 patients experienced progressive disease within 6 months of completion of adjuvant anthracycline therapy. Sites of involvement were as follows: liver involvement, 42 patients (50.6%); lung 24 (28.9%); bone, 49 (59.0%); and skin/lymph nodes, 21 (25.3%). Treatment consisted of vinorelbine 30 mg/m(2) administered on days 1 and 15 every 28 days and fluorouracil 200 mg/m(2)/d given continuously over a 24-hour period. RESULTS: Toxicity was recorded for 441 cycles. The scheme was well tolerated: grade 1/2 nausea/vomiting occurred in 13 patients (15.6%), grade 1/2 diarrhea in nine (10.8%), and grade 2/3 stomatitis in six (7.2%). Three patients (3.6%) experienced grade 3/4 leukopenia and four (4.8%) experienced grade 2/3 anemia. Grade 2/3 neurologic toxicity was observed in three cases (3.6%), and grade 2/3 hand-foot syndrome was observed in three (3.6%). The median relative dose-intensity was 92% and 100% for vinorelbine and fluorouracil, respectively. Six patients (7.2%) attained a complete clinical response and 45 (54.2%) attained a partial response, for an overall response rate of 61.4% (95% confidence interval, 50.9% to 71.9%). Twenty-one patients (25.3%) obtained disease stabilization, and 11 (13.3%) experienced disease progression. Median time to progression in responding patients was 15 months; median overall survival of the entire population was 22 months. CONCLUSION: Vinorelbine associated with protracted infusional fluorouracil is an active and manageable scheme in advanced breast cancer patients previously treated with anthracyclines. The response obtained is durable.

Carboplatin, doxorubicin, and cyclophosphamide versus cisplatin, doxorubicin, and cyclophosphamide: a randomized trial in stage III-IV epithelial ovarian carcinoma.

One hundred sixty-four patients with stage III-IV epithelial ovarian carcinoma were randomized to receive cisplatin (CDDP) 50 mg/mq, doxorubicin 45 mg/mq, and cyclophosphamide 600 mg/mq (PAC) or carboplatin 200 mg/mq, doxorubicin 45 mg/m2, and cyclophosphamide 600 mg/mq (CAC). To administer equitoxic doses at each cycle, the drug dosages were adjusted according to the hematologic toxicities experienced after the previous course; 44.7% of CAC and 21.1% of PAC patients required a dosage reduction at the second course (P = .002). Neither CAC nor PAC caused any clinically relevant neuro-nephrotoxicity; however, CDDP was administered with hydration and forced diuresis, while carboplatin was administered by rapid intravenous (IV) infusion. After six cycles, response rates were superimposable: 62.5% and 66.6% for CAC and PAC, respectively; pathologic complete responses (pCRs) were 16.7% for CAC and 23.2% for PAC; among patients with more than 2 cm residual disease, PAC induced more pCRs than CAC (eight of 52 or 15.4% v one of 42 or 2.4%, P = .07). Median survivals and progression-free survivals (PFSs) were 22.6 and 13.2 months for PAC, and 23.1 and 15.5 months for CAC, respectively; these differences are not significant. In conclusion, this trial demonstrates that equitoxic doses of PAC or CAC result in a similar response rate, PFS, and survival.

Cisplatin and teniposide chemotherapy for advanced non-small cell lung cancer.

30 patients with advanced non-small cell lung cancer were treated with cisplatin 80 mg/m2, day 1, and teniposide 100 or 120 mg/m2, days 1, 3 and 5, every 3 weeks. Myelotoxicity, nausea and vomiting and alopecia were the main side-effects. 8 patients of 26 evaluable had partial responses (31%): 6 had received 120 mg/m2 teniposide and 2 had received 100 mg/m2 teniposide. Overall median survival time was 251 days. Myelotoxicity was significantly lower in patients who received 100 mg/m2 teniposide. Although the number of patients is small and they were not randomly assigned to the two different teniposide doses, it appears that higher dose of teniposide determined a greater degree of myelotoxicity, and also a higher response rate.

Mitomycin C, teniposide, and cisplatin combination chemotherapy for advanced non-small-cell carcinoma of the lung.

A total of 45 patients with advanced non-small-cell lung carcinoma were treated with a combination of cisplatin, teniposide, and mitomycin C. Most subjects exhibited good prognostic factors (performance status, 0-1; minimal weight loss; locoregional disease). Toxicity consisted mainly of myelosuppression and nausea and vomiting. Four patients died of sepsis due to chemotherapy-induced leukopenia. The response rate was 39.5%, with no complete responses being observed; the median duration of partial responses was 231 days and median survival was 243 days. Although the response rate and durations of both response and survival were comparable with those obtained using other cisplating-containing regimens, myelotoxicity was rather pronounced in the present study. Further studies of teniposide in this type of combination are not warranted.

Phase II study of divided-dose vinblastine in advanced breast cancer patients.

The pharmacokinetics of a 5-day, continuous infusion of vinblastine have been reproduced by an i.v. divided bolus at 0 and 48 h [10]; this schedule can be easily applied to outpatients. We treated 26 evaluable patients with refractory, advanced breast cancer with 3.5-4 mg/m2 vinblastine given i.v. by a divided bolus at 0 and 48 h of 21-day cycles. Neurotoxicity and myelosuppression were the main side effects: severe constipation and peripheral neurotoxicity developed in 14% and 3% of the patients, respectively; severe leukopenia and thrombocytopenia occurred in 24% and 10% of the patients, respectively. One partial response, 14 no changes, and 11 progressions were obtained. Our results do not support the use of vinblastine in divided doses in treating this disease.

Paclitaxel administration on days 1 and 8 every 21 days in anthracycline-pretreated metastatic breast cancer patients. A multicenter phase II trial.

Paclitaxel is now included in second- and even first-line regimens in advanced breast cancer. The optimal dose and schedule of this drug, however, still remain a matter of investigation. A group of 57 consecutive patients with advanced breast cancer previously treated with anthracycline-containing regimens were submitted to treatment with single-agent paclitaxel administered at 130 mg/m2 on days 1 and 8 every 21 days. Of the 57 patients, 56 were fully evaluable, and of these 25 had an absolute anthracycline resistance, 14 a relative resistance and 17 were potentially sensitive. The median age of the patients was 57 years (range 33-71 years), their median performance status was 1 (0-3), and 27 (47%) had liver involvement, 17 (30%) lung involvement, 30 (53%) bone involvement and 15 (26%) skin/lymph node involvement. Toxicity was recorded in 295 cycles. This scheme was well tolerated, the dose-limiting toxicities being hematological and neurological. Grade 3/4 leukopenia was observed in 20% of patients at nadir, while grade 3 leukopenia was observed in 3% of patients at recycle. Only one patient experienced febrile neutropenia. Grade 2/3 neurotoxicity was observed in 26% of patients, leading to drug withdrawal in three. The treatment was given on an outpatient basis in all patients and the median relative dose intensity of 86.6 mg/m2 per week was 100% of the planned dose (range 75-100%). Three patients (5%) attained a complete clinical response and 12 (21%) a partial response for an overall response rate of 26% (95% confidence interval 18-38%), while 30 (53%) attained disease stabilization and 11 progressed (19%). Time to progression in responding patients was 10.3 months, and the median overall survival of the entire population was 15.4 months. To conclude, paclitaxel administration on days 1 and 8 every 21 days was active and manageable in advanced breast cancer patients previously treated with anthracyclines. The response obtained was durable.

Brain vasculature and induced ischemia in seizure-prone and non-seizure-prone gerbils.

The relationship between seizure propensity and the vascular anatomy of the anterior cerebral arteries, or stroke induced by unilateral ligation of the common carotid artery, was investigated utilizing well differentiated colonies of seizure-prone (SP) and non-seizure-prone (NSP) gerbils. Twenty SP and 20 NSP gerbils were perfused with a latex dye and the vascular patterns of the anterior cerebral arteries (ACA) were analyzed. In addition, 30 SP and 30 NSP gerbils were subjected to unilateral ligation of the common carotid artery and the number developing stroke (determined by clinical observation as well as by microscopic examination of the brain) was recorded. We found that in all animals the ACAs formed a fused-central vessel which vascularized the olfactory bulbs, as well as two lateral vessels (rostral arteries) that vascularized a previously undescribed nasal plexus. Neither the vascular pattern of the ACA, nor the frequency of occurrence of stroke following unilateral ligation was related to seizure propensity.

Phase II study of alpha-interferon plus bleomycin in advanced non-small cell lung cancer.

A synergistic effect between alpha-Interferon and Bleomycin has been recently shown in in vitro and in vivo experimental systems. Although active, Bleomycin and other antineoplastic drugs give low response rates in non-small cell lung cancer, but, like the other antineoplastic agents, responses are short-lived. We treated 13 patients with advanced non-small cell lung cancer with the combination Bleomycin 15 mg/m2 i.v. at hour 0 and alpha-Interferon 9 X 10(6) U i.m. given at hours 6, 30 and 54. Major side effects were pyrexia, astenia and anorexia; only one case of moderate leukopenia was observed. No major responses were obtained and stable disease lasted a median of 5 months. Further study of this combination is not warranted in patients with pretreated non-small cell lung cancer.

Ifosfamide and etoposide salvage treatment in advanced ovarian cancer.

Twelve FIGO stage III-IV ovarian cancer patients progressing or relapsing after primary cisplatin-containing combination chemotherapy were treated with ifosfamide and etoposide. Only patients with clinically evaluable disease entered the trial. The 12 patients received a median number of 3 courses (range 1-6). No complete or partial response and two disease stabilizations were observed. Ten patients progressed on therapy. The combination of ifosfamide and etoposide does not appear to be an effective salvage treatment for advanced ovarian cancer.