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Vinfunine (VFL) is a novel bifluorinated tubulin-targeted agent of the vinca alkaloids class active in advanced stage breast cancer. We conducted a phase I study combining VFL with doxorubicin (DXR) to define the recommended dose (RD), safety, pharmacokinetic (PK) interaction and efficacy. Two schedules (day 1 every 3 weeks; days 1 and 8 every 3 weeks) were investigated as first line chemotherapy in metastatic breast cancer patients. Thirty-two patients received a total of 162 cycles of the VFL-DXR combination (median 6). The RDs were VFL 250 mg/m(2)/DXR 40 mg/m(2) every 3 weeks for schedule 1 and VFL 120 mg/m(2)/DXR 25 mg/m(2) days 1 and 8 every 3 weeks for schedule 2. The main dose-limiting toxicity was neutropenia. The most frequent non-hematological adverse events were nausea, fatigue, constipation, vomiting, anorexia, stomatitis and dyspnea. Objective response rate was reached in 47.1% of the patients. No PK interaction was observed. VFL-DXR combination is feasible with manageable toxicity. The antitumor activity was promising and supports further evaluation.

Background: Most patients with metastatic breast cancer (MBC) progress after chemotherapy. Cabazitaxel (XRP6258) is a new taxoid that is active in chemotherapy-resistant tumour cell lines. The objectives of this phase I/II study were to assess the maximum tolerated dose (MTD), safety profile, pharmacokinetics, and activity of cabazitaxel plus capecitabine in patients with MBC who had been previously treated with taxanes and anthracyclines., Patients and Methods: In part I, we used a 3+3 dose-escalation scheme to assess the MTD of intravenous cabazitaxel (day 1) with oral capecitabine twice daily (days 1-14) every 3 weeks. In part II, we evaluated the objective response rate (ORR) at the MTD., Results: Thirty-three patients were enrolled and treated (15 in part I; 18 in part II). Cabazitaxel 20mg/m(2) plus capecitabine 1000 mg/m(2) was the MTD. Pharmacokinetic analysis showed no apparent drug-drug interaction. In all patients, the main grade 3-4 toxicities were asthenia (n=5), hand-foot syndrome (n=5), neutropenia (n=21), neutropenic infection (n=1), and neutropenic colitis (n=1). One patient had febrile neutropenia. Antitumour activity was observed at all dose-levels with two complete responses, five partial responses (PRs), and 20 disease stabilisations (seven unconfirmed PR). At the MTD, 21 patients were evaluable for efficacy. The ORR was 23.8% (95% CI: 8.2-47.2%). The median response duration was 3.1 months (95% CI: 2.1-8.4 months), with four of five lasting for more than 3 months. Median time to progression was 4.9 months., Conclusions: Cabazitaxel combined with capecitabine is active, has a safety profile consistent with a taxane plus capecitabine combination and warrants further investigation in patients with MBC., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The majority of human epithelial cancers is frequently characterized by a functional activation of the epidermal growth factor receptor (EGFR)-driven-pathways. Today, two classes of EGFR inhibitors are routinely used in the clinic: anti-EGFR monoclonal antibodies such as cetuximab and panitumumab and small-molecule inhibitors of the EGFR tyrosine kinase activity such as erlotinib and gefitinib. Anti-EGFR therapies have been approved in several countries for the treatment of metastatic nonsmall-cell lung cancer, colorectal cancer, squamous-cell carcinoma of the head and neck, and pancreatic cancer. This article summarizes the clinical evidence of the anticancer activity of anti-EGFR treatment, and considers the current, and controversial, clinical issues with respect to their optimal use in the treatment of patients with cancer. Mechanisms of resistance to anti-EGFR treatment are also briefly discussed.

Activation of de novo lipogenesis in cancer cells is increasingly recognized as a hallmark of aggressive cancers and has been implicated in the production of membranes for rapid cell proliferation. In the current report, we provide evidence that this activation has a more profound role. Using a mass spectrometry-based phospholipid analysis approach, we show that clinical tumor tissues that display the lipogenic phenotype show an increase in the degree of lipid saturation compared with nonlipogenic tumors. Reversal of the lipogenic switch in cancer cells by treatment with the lipogenesis inhibitor soraphen A or by targeting lipogenic enzymes with small interfering RNA leads to a marked decrease in saturated and mono-unsaturated phospholipid species and increases the relative degree of polyunsaturation. Because polyunsaturated acyl chains are more susceptible to peroxidation, inhibition of lipogenesis increases the levels of peroxidation end products and renders cells more susceptible to oxidative stress-induced cell death. As saturated lipids pack more densely, modulation of lipogenesis also alters lateral and transversal membrane dynamics as revealed by diffusion of membrane-targeted green fluorescent protein and by the uptake and response to doxorubicin. These data show that shifting lipid acquisition from lipid uptake toward de novo lipogenesis dramatically changes membrane properties and protects cells from both endogenous and exogenous insults. These findings provide important new insights into the role of de novo lipogenesis in cancer cells, and they provide a rationale for the use of lipogenesis inhibitors as antineoplastic agents and as chemotherapeutic sensitizers., (©2010 AACR.)

Objectives: The primary objectives of this study were to analyse the outcome of patients diagnosed with head and neck soft tissue sarcomas (HNSTS) and to identify relevant prognostic factors. As well as this, we compared the prognostic value of two staging systems proposed by the American Joint Committee on Cancer (AJCC) and the Memorial Sloan-Kettering Cancer Center (MSKCC)., Methods: From 07/1988 to 01/2008, the charts of 42 adult patients were retrospectively reviewed. Potential prognostic factors were analysed according to overall survival (OS), disease-free survival (DFS) and disease-specific survival (DSS)., Results: At 5 years, OS was 57%, DFS 47% and DSS 72%. On univariate analysis, statistically significant prognostic factors were for OS, distant or lymph node metastasis at diagnosis (p=0.032), for DFS, margins after surgery (p=0.007), for DSS, regional or distant metastasis at diagnosis (p=0.002), initial AJCC and MSKCC stage (p=0.018 and p=0.048) and margins after surgery (p=0.042). On multivariate analysis, margins remained statistically significant for DFS (p=0.039) when there was a trend with the initial AJCC stage (p=0.054) for OS. The AJCC staging system was of more prognostic value than the MSKCC staging system., Conclusions: Achieving clear margins after surgery is vital for improved local control and the best chance of survival. Adjuvant chemotherapy and radiotherapy were not shown to provide additional benefit. To better identify prognostic factors, it seems essential to set up national and international databases allowing multicenter registration for those patients.

Trastuzumab (Herceptin, Roche) is a recombinant, humanized monoclonal antibody directed against the neu-HER2 protein, since May 2002 reimbursed in Belgium for the treatment of metastatic HER2+ breast cancer and since June 2007 also in adjuvant therapy of HER2+ early stage breast cancer. The purpose of this study was to estimate the cost-effectiveness from the Belgian health care payer perspective of reimbursing trastuzumab in the Latter indication. A Markov state transition model was designed to adequately capture the natural history and course of disease for early stage breast cancer patients, and to simulate cost and disease progression over a life time perspective. The model estimates differences in outcomes for patients treated with adjuvant trastuzumab during 1 year compared to current therapy, and captures cost consequences and health benefits of trastuzumab treatment. Health benefits were expressed in terms of quality-adjusted life years gained, and future benefits were discounted at 1.5%. Costs were calculated from the perspective of the Belgian authorities' health care budget, and future costs were discounted at 3%. Where relevant, the costs per Markov state were obtained from the IMS Hospital Disease database. Additionally, an expert opinion analysis on resource use during the follow-up of treated early breast cancer patients provided the cost estimates for states with minor or without hospital costs. The incremental cost-effectiveness ratio based on a life time simulation was estimated at Euro 10,315 per quality-adjusted life year gained. It can be concluded that trastuzumab treatment of HER2+ early stage breast cancer patients is cost-effective from the perspective of the Belgian health care authorities.

A 64-year-olf woman has been treated by chemotherapy for a uterine cervical carcinoma with known pathological lymph nodes in the abdomen and in the thorax. She is admitted in our Intensive Care Unit for fever and cardiac tamponade attributed to a large pericardial effusion. No diagnostic could be concluded from the analysis of the liquid or the pericardial biopsy. Complementary investigations are performed and the differential diagnosis of pericardial effusion is discussed in the context of a neoplastic disease.

Background: To assess the safety and preliminary efficacy of concurrent radiotherapy, capecitabine, and cetuximab in the preoperative treatment of patients with rectal cancer., Patients and Methods: Forty patients with rectal cancer (T3-T4, and/or N+, endorectal ultrasound) received preoperative radiotherapy (1.8 Gy, 5 days/week for 5 weeks, total dose 45 Gy, three-dimensional conformal technique) in combination with cetuximab [initial dose 400 mg/m(2) intravenous given 1 week before the beginning of radiation followed by 250 mg/m(2)/week for 5 weeks] and capecitabine for the duration of radiotherapy (650 mg/m(2) orally twice daily, first dose level; 825 mg/m(2) twice daily, second dose level)., Results: Four and six patients were treated at the first and second dose level of capecitabine, respectively. No dose-limiting toxicity occurred. Thirty additional patients were treated with capecitabine at 825 mg/m(2) twice daily. The most frequent grade 1/2 side-effects were acneiform rash (87%), diarrhea (65%), and fatigue (57%). Grade 3 diarrhea was found in 15%. Three grade 4 toxic effects were recorded: one myocardial infarction, one pulmonary embolism, and one pulmonary infection with sepsis. Two patients (5%) had a pathological complete response., Conclusions: Preoperative radiotherapy in combination with capecitabine and cetuximab is feasible with some patients achieving pathological downstaging.

Background: Preoperative radiotherapy has been shown to decrease the local recurrence rate of patients with locally advanced rectal cancer. Capecitabine and oxaliplatin are both active anticancer agents in the treatment of patients with advanced colorectal cancer and have radiosensitizing properties. Therefore, these drugs would be expected to improve effectiveness of preoperative radiotherapy in terms of local control and prevention of distant metastases., Patients and Methods: Forty patients with rectal cancer (T3-T4 and/or N+) received radiotherapy (1.8 Gy, 5 days a week over 5 weeks, total dose 45 Gy, 3D conformational technique) in combination with intravenous oxaliplatin 50 mg/m2 once weekly for 5 weeks and oral capecitabine 825 mg/m2 twice daily on each day of radiation. Surgery was performed 6-8 weeks after completion of radiotherapy. The main end points were safety and efficacy as assessed by the pathological complete response (pCR)., Results: The most frequent grade 3/4 adverse event was diarrhea, occurring in 30% of patients. pCR was found in five (14%) patients. According to Dworak's classification, good regression was found in six (18%) additional patients., Conclusions: Combination of preoperative radiotherapy with capecitabine and oxaliplatin is feasible for downstaging rectal cancer.

This study was initiated to evaluate the efficacy of luteinizing hormone-releasing hormone (LH-RH) agonists in protecting premenopausal patients against the adverse gynaecological effects induced by tamoxifen. Between January 1998 and January 2000, 85 premenopausal breast cancer patients were included in this prospective study. All were to receive LH-RH agonists and tamoxifen for a minimum of two years. All patients underwent a pretreatment gynaecological evaluation and annual follow-up. Bone density was also measured at the start of treatment and then after 2, 3 and 4 years. Pretreatment evaluation revealed 2 polyps. At one and two years of follow-up, no abnormal symptoms were noted and echographic findings were normal. At three years of follow-up, a polyp associated with adnexal masses was discovered. Histology revealed ovarian and endometrial metastases of infiltrating lobular breast carcinoma. Bone density evaluation after 2, 3 and 4 years of treatment showed no significant bone loss. LH-RH agonists offer safe protection against the gynaecological side-effects of tamoxifen in premenopausal breast cancer patients.

Utilization of chemotherapy for treatment of tumors is mainly limited by its hematological toxicity. Because of the low level expression of drug resistance genes, transduction of hematopoietic progenitors with multidrug resistance 1 (MDR1) or multidrug resistance-associated protein 1 (MRP1) genes should provide protection from chemotherapy toxicity. Successful transfer of drug resistance genes into hematopoietic cells might allow the administration of higher doses of chemotherapy and, therefore, increase regression of chemosensitive tumors. In addition, this approach can be used to select in vivo transduced cells by their enrichment after administration of cytotoxic drugs. Our group has studied the potential value of MRP1 to protect hematopoietic cells. The interest in the use of MRP1 as an alternative to MDR1 gene transfer for bone marrow protection lies in its different modulation. Indeed, classical P-gp reversal agents, tested in clinic to decrease MDR1 tumor resistance, have little or no effect on MRP1 function. This would allow, in the same patient, the use of reversal agents to decrease P-gp tumor resistance without reversing bone marrow protection of the transduced hematopoietic cells provided by MRP1. We constructed two different MRP1-containing vectors with either the Harvey retroviral long terminal repeat (LTR) or phosphoglycerate kinase (PGK) as promoters and generated ecotropic producer cells. MRP1 transduced fibroblasts were more resistant to doxorubicin, vincristine, and etoposide and their chemoprotection was increased after selection with chemotherapeutic agents in the presence of glutathione, a co-factor for MRP1 function. Lethally irradiated mice were engrafted with bone marrow (BM) cells transduced with MRP1 vectors (PGK promoter). We demonstrated that high expression of MRP1 in murine hematopoietic cells reduces doxorubicin-induced leukopenia and mortality. In addition, in vivo selection of MRP1-transduced BM cells was achieved following doxorubicin administration and allowed a better chemoprotection after the second chemotherapy cycle.

Tumor-specific immune tolerance limits the effectiveness of cancer vaccines. In addition, tumor vaccines alone have a limited potential for the treatment of measurable tumor burdens. This highlights the importance of identifying more potent cancer vaccine strategies for clinical testing. We tested immune-modulating doses of chemotherapy in combination with a granulocyte/macrophage-colony stimulating factor (GM-CSF)-secreting, HER-2/neu (neu)-expressing whole-cell vaccine as a means to treat existing mammary tumors in antigen-specific tolerized neu transgenic mice. Earlier studies have shown that neu transgenic mice exhibit immune tolerance to the neu-expressing tumors similar to what is observed in patients with cancer. We found that cyclophosphamide, paclitaxel, and doxorubicin, when given in a defined sequence with a GM-CSF-secreting, neu-expressing whole-cell vaccine, enhanced the vaccine's potential to delay tumor growth in neu transgenic mice. In addition, we showed that these drugs mediate their effects by enhancing the efficacy of the vaccine rather than via a direct cytolytic effect on cancer cells. Furthermore, paclitaxel and cyclophosphamide appear to amplify the T helper 1 neu-specific T-cell response. These findings suggest that the combined treatment with immune-modulating doses of chemotherapy and the GM-CSF-secreting neu vaccine can overcome immune tolerance and induce an antigen-specific antitumor immune response. These data provide the immunological rationale for testing immune-modulating doses of chemotherapy in combination with tumor vaccines in patients with cancer.

Cancer vaccines are on the threshold of taking their place alongside the more traditional cancer treatment modalities of surgery, radiation therapy and chemotherapy. The toxicology and immunopharmacology of therapeutic cancer vaccines, particularly those that secrete granulocyte macrophage colony stimulating factor (GM-CSF), are currently under active clinical investigation. Interestingly, drugs traditionally used for tumor cytoreduction can have both positive and negative effects on host immunity. Exploration of the potential pharmacodynamic interactions of antineoplastic drugs with GM-CSF-secreting vaccines has revealed that low doses of some chemotherapeutics can augment the antitumor immunity induced by GM-CSF-secreting vaccines. These interactions will require thorough preclinical evaluation to maximize the clinical impact of this type of therapeutic cancer vaccine.

HER-2/neu (neu) transgenic mice (neu-N mice), which express the nontransforming rat proto-oncogene, demonstrate immunological tolerance to neu that is similar to what is encountered in patients with neu-expressing breast cancer. We have shown previously that a significant increase in neu-specific T cells, but no induction of neu-specific antibody, is seen after neu-specific vaccination in neu-N mice. In contrast, a significant induction of both neu-specific T-cell and antibody responses is found in nontoleragenic FVB/N mice after vaccination. These mice are fully protected from a s.c. challenge with NT cells, a mammary tumor cell line derived from a spontaneous tumor that arose in a neu-N mouse, whereas neu-N mice are not. In this study, we demonstrate that CD4+ T cell-depleted FVB/N mice show no induction of neu-specific IgG after vaccination and are unable to reject an NT challenge (0 of 10 mice were tumor free). Conversely, the depletion of natural killer cells has no effect on vaccine-mediated tumor rejection (100% of mice were tumor free). In CD8+ T cell-depleted animals, where vaccine-induced neu-specific IgG titers were normal, NT growth was delayed, but only 10% of mice remained tumor free, demonstrating that neu-specific IgG alone is insufficient for protection from NT challenge. To directly assess the necessity for the combination of neu-specific cellular and humoral immune responses, severe combined immunodeficient mice were given an adoptive transfer of CTLs plus IgG derived from FVB/N mice. Animals that were given CTLs that recognized an irrelevant antigen plus neu-specific IgG developed tumors at a rate similar to CD8+ T cell-depleted FVB/N mice. Animals receiving an adoptive transfer of neu-specific CTLs plus control IgG derived from naive FVB/N mice were only partially protected from NT challenge (50% of animals were tumor free). However, only animals receiving the combination of neu-specific CTLs and neu-specific IgG were fully protected from NT challenge (100% of animals were tumor free). These studies specifically define the immunological requirements for the eradication of neu-expressing tumors in this model system, demonstrating that both cellular and humoral neu-specific responses are necessary for protection from an NT challenge. These data suggest that vaccines optimized to induce maximal T- and B-cell immunity to neu, and possibly to similar putative tumor-rejection antigens, may lead to more potent in vivo antitumor immunity.

HER-2/neu (neu-N) transgenic mice, which express the nontransforming rat proto-oncogene, develop spontaneous focal mammary adenocarcinomas beginning at 5-6 months of age. The development and histology of these tumors bears a striking resemblance to what is seen in patients with breast cancer. We have characterized the immunological responses to HER-2/neu (neu) in this animal model. neu-positive tumor lines, which were derived from spontaneous tumors that formed in neu-N animals, are highly immunogenic in parental, FVB/N mice. In contrast, a 100-fold lower tumor challenge is sufficient for growth in 100% of transgenic animals. Despite significant tolerance to the transgene, neu-specific immune responses similar to those observed in breast cancer patients can be demonstrated in neu-N mice prior to vaccination. Both cellular and humoral neu-specific responses in transgenic mice can be boosted with neu-specific vaccination, although to a significantly lesser degree than what is observed in FVB/N mice, indicating that the T cells involved are less responsive than in the nontoleragenic parental strain. Using irradiated whole-cell and recombinant vaccinia virus vaccinations we are able to protect neu-N mice from a neu-expressing tumor challenge. T-cell depletion experiments demonstrated that the observed protection is T cell dependent. The vaccine-dependent neu-specific immune response is also sufficient to delay the onset of spontaneous tumor formation in these mice. These data suggest that, despite tolerance to neu in this transgenic model, it is possible to immunize neu-specific T cells to achieve neu-specific tumor rejection in vivo. These transgenic mice provide a spontaneous tumor model for identifying vaccine approaches potent enough to overcome mechanisms of immune tolerance that are likely to exist in patients with cancer.

Utilization of chemotherapy for the treatment of tumors is mainly limited by its hematological toxicity. Because of the low-level expression of drug resistance genes, transduction of hematopoietic progenitors with multidrug resistance 1 (MDR1) or multidrug resistance-associated protein (MRP) genes should provide protection from chemotherapeutic agent toxicity. Successful transfer of drug resistance genes into hematopoietic cells may allow the administration of higher doses of chemotherapy and, thus, increase regression of chemosensitive tumors. The interest in the use of MRP as an alternative to MDR1 for bone marrow protection lies in its different modulation. This would allow, in the same patient, the use of MDR1 reversal agents to decrease MDR1 tumor resistance without reversing bone marrow (BM) protection of the MRP-transduced hematopoietic cells, since MRP expression is not reversed by these agents. We have constructed MRP-containing retroviral vectors using the phosphoglycerate kinase promoter and generated ecotropic producer cells. Lethally irradiated mice were engrafted with BM cells transduced by coculture with MRP producer cells. Evidence of long-term (9 months) gene transfer was provided by PCR of peripheral blood from MRP-transduced mice. Southern blot analysis confirmed the integrity of the provirus in the MRP-transduced mice. Long-term MRP expression (>5 months) was detected by RT-PCR and fluorescence-activated cell sorting of blood from living mice. High-level expression of MRP in murine hematopoietic cells reduces doxorubicin-induced leukopenia and mortality. Furthermore, we show in vivo selection of MRP-transduced cells following doxorubicin administration, with better and more significant chemoprotection after the second chemotherapy cycle. These data indicate that MRP retroviral gene transfer may be useful for chemoprotection and selection.

A 39-year-old woman had alcoholic ketoacidosis complicated by reversible life-threatening myocardial dysfunction. This complication occurred a few hours after correction of acidosis in association with severe hypophosphatemia. A marked improvement in clinical, echocardiographic, and hemodynamic features was associated with the normalization of the serum phosphorus level. This case illustrates a rare complication of hypophosphatemia, emphasizing the need for emergency physicians to consider this metabolic disorder in the treatment of patients with alcoholic ketoacidosis. The pathogenesis of hypophosphatemia in alcoholic ketoacidosis, its potential role in myocardial dysfunction, and its therapeutic implications in emergencies are discussed.

The association of gastric leiomyoblastomas, pulmonary chondromas and extra-adrenal paragangliomas has been called "Carney's Triad" since 1977. It is incomplete when only two of these lesions are present. 42 cases has been published. We report observations of two young women with gastric leiomyoblastomas and pulmonary chondromas; one of them also had an adrenocortical adenoma.

The authors report the case of a patient with drug-resistant atrial fibrillation, who developed, for more than 2 hours, a well-tolerated attack of palpitations, after taking 500 mg of flecainide acetate. The Holter monitoring demonstrated atrial flutter with 1:1 AV conduction and a ventricular rate at 220 bpm. This atrial pro-arrhythmic effect is rare and the mechanism is discussed.

Two hundred seventy severely hypoxemic (PaO2 < or = 55 mm Hg: mean +/- SD = 48 +/- 6) COPD patients (232 men) were selected for long-term oxygen therapy (LTOT). They were old (mean = 66 +/- 8 years), with severe airflow limitation (FEV1 = 30 +/- 12 percent of predicted), some CO2 retention (PaCO2 = 47 +/- 9 mm Hg), and compensated respiratory acidosis. Eighteen percent of the patients presented some complicating pleuropulmonary diseases (pleural thickening, sequelae of tuberculosis, etc). Overall survival proportion was poor: 70, 50, and 43 percent at 1, 2, and 3 years, respectively. The Cox model showed that the factors which independently reduced survival were lower CO transfer coefficient, smaller intrathoracic gas volume, more severe bronchial obstruction, the fact that oxygen administration did not increase PaO2 above 65 mm Hg, increasing age, and the presence of chest wall abnormalities. When the patients were divided into three groups according to mortality risk, the mean clinical and functional profile of the high-mortality risk group was consistent with the prevalence of emphysematous lesions. Moreover, the best survivors fitted better into the "bronchitic" type; they showed a higher mean PaCO2, suggesting that some degree of hypoventilation could delay muscular fatigue and improve survival. The difference in the proportion of "emphysematous" and "bronchitic" patients is a possible explanation for the variability of the mortality rate reported in literature.

Thirty-nine asthmatic patients hypersensitive to Dermatophagoides pteronyssinus were treated for a total of 4 yr with injections of complexes made of allergen and autologous specific antibodies. The results obtained throughout the first 2 yr of a double-blind placebo-controlled trial have been published (1) and we now report the results of such therapy during an additional 2 yr. Three groups of patients had been defined: Groups A and B were comprised of patients treated with either "higher" doses of complexes (Group A) or "lower" doses (Group B), whereas Group C received the placebo preparation. Four injections of complexes were performed during the third yr and none during the fourth yr. The clinical benefit resulting from such injections was maintained until the end of the study, whereas medication intake, especially systemic or high doses of inhaled corticosteroids, was much reduced. Skin reactivity to allergen was significantly decreased in both treated groups. Bronchial provocation tests were carried out at 1-yr intervals with either allergen or acetylcholine (ACh). Reactivity to allergen inhalation was significantly decreased at each time point. Reactivity to ACh was significantly decreased at the end of Years 3 and 4. Fifty percent of treated patients who underwent bronchial challenges lost their bronchial reactivity to the highest concentrations of both allergen and ACh. A significant improvement in the basal lung function was observed in both treated groups. The long-term effects of immunotherapy with allergen-antibody complexes in allergic asthma patients thus include reduction in nonspecific bronchial reactivity.

Fifty-four newly diagnosed patients with advanced Hodgkin's disease were randomized between two alternating non cross-resistant chemotherapies: MOPP-ABVD (MOPP: Mustine, Vincristine, Procarbazine, Prednisone-ABVD: Adriamycin, Bleomycin, Vinblastine, Dacarbazine) and MOPP-ABVD-CEM (CEM: Carmustine, Etoposide, methyl-GAG). There were no significant differences between the two therapies as far as complete remission, survival, relapse free survival and toxicity were concerned. This study does not support the use of MOPP-ABVD-CEM for improving the long-term outcome of patients with advanced Hodgkin's disease.

Complexes made from antigen and specific antibodies have been used to suppress specific antibody production. This property is of potential therapeutic interest in immediate hypersensitivity states which are characterized by hyperproduction of IgE antibodies. We report here on the use of antigen-antibody complexes in patients with hypersensitivity to grass pollen. Specific anti-allergen antibodies were prepared by immunoadsorption from the serum of hypersensitive individuals and mixed with grass pollen allergens to form complexes in antibody excess. These complexes were used in a strictly autologous manner for inoculating patients prior to and during a pollen season. The study comprised two randomly defined groups of 15 patients who were inoculated intradermally either with a preparation of allergen-antibody complexes or with the carrier buffer, according to a double-blind protocol. Diary cards were used to follow nasal and ocular symptoms, bronchial asthma and medication intake. Specific IgE antibodies were assayed during the trial and 1 year afterwards. Inoculation of allergen-autologous antibody complexes was well tolerated. It significantly reduced ocular symptoms (Mann-Whitney U-test, P less than 0.05), bronchial asthma during the first part of the season (Mann-Whitney U-test, P less than 0.001) and drug intake (Mann-Whitney U-test, P less than 0.001). This treatment prevented the seasonal increase in specific IgE antibodies, whose production continued to decrease after the pollen season. These effects were obtained within a few weeks of treatment, using a cumulative amount of allergen 100-fold lower than the amount which would have been used for a conventional hyposensitization.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchial reactivity to increasing concentrations of acetylcholine (from 0.01 to 10 mg X ml-1) was studied in 84 asthmatic patients during a remission period. Three groups were identified based on decreasing reactivity : group 1 : 57 patients (68%) who exhibited a decrease equal or of more than 20% of forced expiratory volume per second (FEV1) and a decrease equal or of more than 35% of specific airway conductance (sGaw); group 2: 16 patients (19%) with a decrease in FEV1 of less than 20%, but a decrease in sGaw still equal or superior to 35%; group 3 : 11 patients (13%) with a less than 20% decrease in FEV1 and a less than 35% decrease of sGaw. Basal measurements of FEV1 and sGaw gave significantly lower values in group 1 than in group 2 and in group 2 than in group 3. A strong positive relationship was found between initial FEV1 (% of predicted) and acetylcholine concentration giving a fall of 20% in FEV1 (PD20-FEV1) (r = 0.87; p less than 0.001); a weak but still statistically significant relationship existed between initial sGaw and PD35-sGaw (r = 0.38; p less than 0.01). Twenty-five patients with allergic asthma were submitted to an inhalation test with Dermatophagoides pteronissimus (Dpt). Bronchial reactivity to Dpt was significantly correlated with acetylcholine (r = 0.9; p less than 0.001). Twenty-four hours after Dpt exposure, seven patients (28%) still presented bronchial obstruction. Eleven patients without persistent obstruction 24 h after Dpt exposure were resubmitted to acetylcholine; bronchial reactivity was found increased when compared to the initial acetylcholine-induced bronchospasm.(ABSTRACT TRUNCATED AT 250 WORDS)

A multi-center, open trial was conducted to determine the maximal tolerable dose of carboplatin in combination with conventional doses of both etoposide and an anthracycline for the treatment of previously untreated small cell lung cancer (SCLC) patients. Ninety-five patients [48 with limited disease (LD) and 47 with extensive disease (ED)] received a total of 376 courses of treatment. Carboplatin was given on day 1 at a dose of 250 mg m-2 in 60 courses, 300 mg m-2 in 69, 330 mg m-2 in 236 and 350 mg m-2 in 11, with 120 mg m-2 etoposide on days 1, 3 and 5 and either 40 mg m-2 adriamycin or 60 mg m-2 epirubicin on day 1. Epirubicin was not administered before carboplatin reached the dose of 330 mg m-2. Courses were repeated every 3 weeks. The main toxicity was hematological. The first course of therapy induced a dose-dependent decrease of leucocyte, neutrophil and platelet counts: all patients, except one, who received 350 mg m-2 carboplatin had a neutropenia below 200 microliters-1 and a thrombopenia below 100,000 microliters-1. Three patients died of septicemia. Other toxicities were well tolerated. After three courses, patients were re-staged by performing a mandatory fiberoptic bronchoscopy and a thoracic computed axial tomography (CAT). The overall objective response rate for 86 evaluable patients was 91% (98% for LD) with 21% complete remissions (30% for LD). All 23 hepatic and six brain sites, evaluable after chemotherapy alone, responded.(ABSTRACT TRUNCATED AT 250 WORDS)