PO-01 - Congestive heart failure is an independent risk factor for venous thromboembolism and mortality in cancer patients.

INTRODUCTION: Prediction of venous thromboembolism (VTE) occurrence in cancer patients using individual risk factors may contribute to preventing the burden of disease associated with VTE. Congestive heart failure in patients with cancer may increase the risk of VTE and worsen the prognosis. AIM: We sought to investigate the association of congestive heart failure and occurrence of VTE in cancer patients, specifically with consideration for the poor prognosis in patients with heart failure and cancer. MATERIALS AND METHODS: Hospitalized and ambulatory cancer patients were included in the prospective Vienna Cancer and Thrombosis Study (CATS) in search of risk factors for occurrence of VTE. Cancer entities and comorbidities were recorded at baseline and verified using medical documentation including a diagnosis of congestive heart failure. The occurrence of VTE events was compiled via mail and telephone follow-ups for two years. Risk of VTE occurrence was calculated in the competing risk regression model, considering death as a competing event during follow-up. RESULTS: In the current analysis 1,433 patients (632 women, 44.1%) with a median age of 61 years (25th-75th percentile: 52-75) were included. During the observation period, 108 (7.5%) VTE events and 522 (36.4%) deaths occurred. The median observation time was 729 days (233-731), and 34 patients (2.3%) had diagnosed congestive heart failure at the time of study inclusion, 12 of which had NYHA II-IV and 22 unspecified congestive heart failure. In the group of heart failure patients, 6 had VTE events and 23 died. In univariate competing risk analysis, the risk of VTE occurrence was increased 2.6-fold in patients with heart failure compared to those without a diagnosis of heart failure (SHR 2.58, 95% CI 1.13-5.92, p=0.025). After multivariable adjustment for age, BMI, gender, diabetes, history of myocardial infarction or stroke, use of antiplatelet drugs, cancer site, hypertension, D-Dimer level and peripheral arterial disease, the risk of VTE in heart failure patients was 3-times the risk of patients without heart failure (HR 3.07, 95% CI 1.15-8.19, p=0.025). Further, congestive heart failure was a strong predictor of mortality (HR 1.70, 95% CI 1.10-2.65, p=0.018). CONCLUSIONS: Congestive heart failure is not only a risk factor for mortality in cancer patients, but also an independent predictor of VTE occurrence. In order to prevent VTE and the associated burden, patients with cancer and congestive heart failure may benefit from thromboprophylaxis.

A virosomal formulated Her-2/neu multi-peptide vaccine induces Her-2/neu-specific immune responses in patients with metastatic breast cancer: a phase I study.

We have previously shown in mice that vaccination with three Her-2-peptides representing B-cell epitopes of the extracellular domain of Her-2/neu induces Her-2/neu-specific IgG antibodies with strong anti-tumor activity in vitro and in vivo. We have now finalized a phase I clinical trial with an anti-Her-2/neu vaccine-construct of immunopotentiating reconstituted influenza virosomes with the three peptides in patients with metastatic breast cancer (MBC). Ten MBC patients with low protein overexpression of Her-2/neu of MBC (+ or ++ upon immunohistochemistry, FISH negative) and positive hormone receptor status were enrolled in a single center phase I study. The virosomal formulated vaccine, consisting of 10 microg/peptide, was intramuscularly applied three times on days 1, 28, and 56. The primary endpoint of the study, which lasted 12 weeks, was safety, the secondary endpoint immunogenicity. Local erythema at the injection site was the only vaccine-related side effect occurring in four patients. In 8 of 10 patients an increase in peptide-specific antibody titer measured by ELISA was found. Importantly, the induced antibodies were also directed against the native Her-2/neu protein. Cellular immune responses, as measured by in vitro production of IL-2, IFN-c, and TNF-a of PBMCs showed a marked increase after vaccination in the majority of vaccinees. Notably, the number of CD4+CD25+Foxp3+T regulatory cells, which were significantly increased compared to healthy controls prior to vaccination, was markedly reduced following vaccination. In all, the immunological responses after vaccination indicated that the patients in stage IV of disease were immunocompetent and susceptible to vaccination. The Her-2/neu multipeptide vaccine was safe, well tolerated and effective in overcoming immunological tolerance to Her-2/neu. The induction of anti-Her-2-specific antibodies could result in clinical benefit comparable to passive anti-Her-2 antibody therapy.

Third consensus on medical treatment of metastatic breast cancer.

BACKGROUND: Treatment options for patients with metastatic breast cancer (MBC) include a rapidly expanding repertoire of medical, surgical and supportive care measures. DESIGN: To provide timely and evidence-based recommendations for the diagnostic workup and treatment of patients with MBC, an international expert panel reviewed and discussed the evidence available from clinical trials regarding diagnostic, therapeutic and supportive measures with emphasis on their impact on the quality of life and overall survival of patients with MBC. RESULTS: Evidence-based recommendations for the diagnostic workup, endocrine therapy, chemotherapy, use of targeted therapies and bisphosphonates, surgical treatment and supportive care measures in the management of patients with MBC were formulated. CONCLUSIONS: The present consensus manuscript updates evidence-based recommendations for state-of-the-art treatment of MBC depending on disease-associated and biological variables.

Second consensus on medical treatment of metastatic breast cancer.

The present consensus manuscript defines evidence-based recommendations for state-of-the-art treatment of metastatic breast cancer depending on disease-associated and biologic variables.

Deficiences in phenotype expression and function of dentritic cells from patients with early breast cancer.

PURPOSE: Monocytes derived from patients with early breast cancer (EBC) have shown functional deficiencies. These functional deficiencies are characterized by changes in phenotype and morphology. We have expanded these investigations to dendritic cells generated from monocytes from patients with early breast cancer. - PATIENTS AND METHODS: Peripheral blood from 36 patients with EBC and from 26 healthy age-matched women was drawn and prepared for ex vivo generation of dendritic cells (DC) by incubation with granulocyte/macrophage-colony stimulating factor (GM-CSF) and interleukin 4 (IL4). The phenotype of DC was examined by flow-cytometry. T cell - proliferation was induced with tetanus toxoid pulsed autologous dendritic cell. - RESULTS: Dendritic cells generated from monocytes from EBC-patients showed a significantly lower expression of the phenotype-associated antigens CD1a, CD83, CD80, CD86 and CD54 than the dendritic cells from healthy controls. T cell - proliferation in response to TT-pulsed autologous dendritic cells was significantly decreased when induced with dendritic cells from patients with early breast cancer, when compared to healthy controls. Morphologically, only dendritic cells from healthy women possessed prominent dendrites indicating maturity. - CONCLUSIONS: These findings indicate that dendritic cells generated from monocytes from patients with early breast cancer express an immature phenotype, exhibit immature morphology and show functional deficits when compared to the cells derived from healthy age-matched controls. Whether these findings offer a potential target for therapeutic interventions remains to be elucidated.

Trail-induced apoptosis and interaction with cytotoxic agents in soft tissue sarcoma cell lines.

Five human soft tissue sarcoma (STS) cell lines (HTB-82 rhabdomyosarcoma, HTB-91 fibrosarcoma, HTB-92 liposarcoma, HTB-93 synovial sarcoma and HTB-94 chondrosarcoma) were analysed for their sensitivity to tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and the function of the TRAIL apoptotic pathway in these cells. TRAIL induced significant apoptosis (>90%) in HTB-92 and HTB-93 cells, whereas no effect was observed in HTB-82, HTB-91 and HTB-94 cells. TRAIL-Receptor 1 (TRAIL-R1) was expressed in TRAIL-sensitive HTB-92 and HTB-93 cell lines, but not in TRAIL-resistant HTB-91 and HTB-94 cells. HTB-82 cells, which expressed the long (c-FLIP(L)) and short (c-FLIP(S)) splice variants of the FLICE-like inhibitory protein (FLIP), were resistant to TRAIL in spite of the presence of TRAIL-R1. TRAIL-R2,-R3,-R4 and osteoprotegerin (OPG) expression did not correlate with TRAIL sensitivity. Coincubation of TRAIL and doxorubicin led to the overexpression of TRAIL-R2 resulting in a synergistic effect of doxorubicin and TRAIL in TRAIL-sensitive cell lines and in the overcoming of TRAIL-resistance in all of the TRAIL-resistant cell lines, except HTB-91, which lacked caspase 8 expression. These data suggest that TRAIL, either as a single agent or in combination with cytotoxic agents, might represent a new treatment option for advanced STS, which constitutes a largely chemotherapy-resistant disease.

Anti-Her-2/neu antibody induces apoptosis in Her-2/neu overexpressing breast cancer cells independently from p53 status.

Anti-Her-2/neu antibody is known to induce apoptosis in HER-2/neu overexpressing breast cancer cells. However, exact regulatory mechanisms mediating and controlling this phenomenon are still unknown. In the present study, we have investigated the effect of anti-Her-2/neu antibody on apoptosis of HER-2/neu overexpressing human breast cancer cell lines SK-BR-3, HTB-24, HTB-25, HTB-27, HTB-128, HTB-130 and HTB-131 in relation to p53 genotype and bcl-2 status. SK-BR-3, HTB-24, HTB-128 and HTB-130 cells exhibited mutant p53, whereas wild type p53 was found in HTB-25, HTB-27 and HTB-131 cells. All seven cell lines weakly expressed bcl-2 protein (10-20%). Anti-Her-2/neu antibody, irrespective of p53 and bcl-2 status, induced apoptosis in all 7 cell lines dose- and time-dependently and correlated with Her-2/neu overexpression. In addition, incubation of cell lines with anti-Her-2/neu antibody did not alter p53 or bcl-2 expression. Anti-HER-2/neu antibody did not induce apoptosis in HER-2/neu negative HBL-100 and HTB-132 cell lines. Our results indicate that within the panel of tested breast cancer cell lines, anti-Her-2/neu antibody-induced apoptosis was independent from the presence of intact p53.

Docetaxel as rescue medication in anthracycline- and ifosfamide-resistant locally advanced or metastatic soft tissue sarcoma: results of a phase II trial.

BACKGROUND: Metastatic soft tissue sarcoma not amenable to curative surgery has a dismal prognosis. Aggressive treatment with anthracyclines and ifosfamide represents the current therapeutic mainstay in these patients, most of whom succumb to relapses. Thus, the efficacy of subsequent therapeutic approaches has to be weighed against toxicity caused by palliative treatment. PATIENTS AND METHODS: Patients with locally advanced or metastatic soft tissue sarcoma refractory to treatment with anthracyclines and ifosfamide were enrolled into the present phase II study. Patients were assigned to receive docetaxel at 100 mg/m2 every three weeks. In case of severe toxicity, patients were switched to a weekly schedule of docetaxel (40 mg/m2). RESULTS: A total of 106 cycles (80% at the scheduled 100 mg/m2 dose level) were administered in 27 patients. Partial response was observed in 4 (15%) patients and 4 (15%) patients experienced disease stabilization. Median progression free survival and overall survival were 2.4 (range: 0.9-23.9) and 7.7 (range: 1.0-44.3) months, respectively. Upon renewed progression, three patients initially responsive to treatment with docetaxel were successfully reinduced by treatment with docetaxel. The safety profile of docetaxel was tolerable and the administration mostly manageable on an outpatient basis. CONCLUSIONS: Our results suggest that docetaxel represents an efficacious and tolerable treatment in a minority of patients refractory to standard treatment. There is a need for better identification of patients most likely to benefit from salvage treatment with docetaxel.

Decrease of duration and symptoms in chemotherapy-induced oral mucositis by topical GM-CSF: results of a prospective randomised trial.

We have conducted a prospective controlled randomised clinical study testing for the efficacy of topical GM-CSF (molgramostim), as compared to the combined topical use of an antiseptic agent (povidone-iodine) and amphotericin B (AA) in patients with chemotherapy-induced mucositis World Health Organization (WHO) grades I-III. 31 patients (17 females, 14 males) developing oral mucositis following the administration of 5-fluorouracil (5-FU)-based chemotherapy were entered into the present trial. 15 patients were randomised to receive GM-CSF mouthwashes, whereas 16 patients were randomised into the control arm to receive AA. Reported history (P=0.6109) and grading of oral mucositis (2.1+/-0.7, respectively; P=0.9867) were balanced and equally distributed between the two groups. The mean size of lesions of oral mucositis was 1.5+/-0.6 cm (range: 0.7-2.5 cm) in the GM-CSF group and 1.2+/-0.5 cm (range: 0.5-2.5 cm) in the AA group (P=0.08), respectively. The mean number of oral mucositis lesions was 1.9+/-1.1 (range: 1-4) in the GM-CSF group and 2.1+/-1.2 (range: 1-4) in the AA group (P=0.63), respectively. None of the patients had previously received colony stimulating factors either topically or systemically. Treatment for oral mucositis was initiated on day 2.7+/-1.2 (range: day 1-8) after onset of symptoms in the GM-CSF group and on day 1.8+/-1.4 (range: day 1-3; P=0.11) in the AA group. The topical application of GM-CSF resulted in a significantly shorter duration and quicker resolution of oral mucositis, as compared to AA including both, pretreatment plus treatment periods (5.3+/-2.5 versus 8.1+/-1.5 days; P=0.0008) as well as the necessary duration of treatment needed until complete remission of lesions (2.8+/-0.7 versus 6.3+/-1.1 days; P<0.0001). A systemic effect of topical GM-CSF upon the number of peripheral blood leukocytes or granulocytes was excluded. We conclude that the topical application of GM-CSF by mouthwash significantly abbreviated the duration and relieved patients from symptoms of chemotherapy-induced mucositis and was superior to the topical application of AA.

[Acceptance of and satisfaction with medical information provided to cancer patients]. / Annahme von Aufklärungsinhalten und Zufriedenheit bei Krebspatienten.

BACKGROUND: Medical information to oncologic patients about their disease as well as regularly updated information about the course of their disease and the therapeutic success are essential components of a comprehensive treatment in cancer patients. STUDY GOAL: The quality of the patient-doctor-interaction as well as the hospital preference of oncologic patients were evaluated by a questionnaire at the Oncologic Out-Patient Clinic of the University Hospital of Vienna. METHODS: 350 questionnaires containing 12 questions about medical information, anti-cancer therapy, suggestions for improvement and hospital preference were distributed. The questions were correlated with the patients' demographic and medical data. RESULTS: Out of 350 questionnaires, 234 (67%)--160 (68%) by women and 74 (32%) by men--were returned. 75% of the patients were satisfied with the provided medical information. In contrast, 12% of patients felt incompletely informed about their particular cancer and 19% were unsatisfied with their state of information about the actual status of their disease. Our institution was mostly visited for quality-associated reasons and only in 3% for pragmatic reasons. 58% of the patients had no suggestions for improvement of medical care, although 28% of the patients wanted to spend more time with their doctors, 10% asked for more psychological care and 8% for additional alternative therapeutic modalities. CONCLUSION: The Oncologic Out-Patient Clinic is frequented mainly for quality-associated reasons. Although satisfaction with medical management is very high, there remains space for improvement of information about the underlying disease and its current status.

[Tumor markers]. / Tumormarker.

Tumour markers are substances developed in or induced by tumour cells and secreted into body fluids in which they can be quantified by non-invasive analyses. The malignant transformation of cells leads to increased concentrations of tumour markers and thus they can indicate malignant diseases. It appears, however, that other proliferative processes, i.e. inflammatory and benign transformations are also able to induce the rise of tumour marker levels. Due to their low sensitivity and specificity, tumour markers--except for PSA--are not useful in diagnosis and screening. Though disseminated malignant disorders are associated with high tumour marker levels, a correlation between their concentration and the tumour volume is not clearly approved. The use of tumour markers seems established for the follow-up after curative surgery and for the treatment and monitoring of palliative therapy.

Soluble ICAM-1 in breast cancer: clinical significance and biological implications.

OBJECTIVES: In previous experiments, we demonstrated a decreased expression of intercellular adhesion molecule I (ICAM-1) on both tumour cells and antigen-presenting cells derived from patients with breast cancer, resulting in an abrogation of antigen presentation and tumour cell lysis. Recently, increased levels of a soluble isoform of ICAM-1 (sICAM-1) have been detected in the sera of breast cancer patients. The present investigation was performed in order to investigate the biological relevance of serum concentrations and the effects of sICAM-1 in patients with breast cancer. PATIENTS AND METHODS: sICAM-1 was determined using a sandwich enzyme immunoassay on sera from 88 patients with various stages of breast cancer and correlated with clinical parameters. The effect of sICAM-1 present in the sera of patients with breast cancer upon unspecific and anti-Her-21/neu antibody-mediated cytotoxicity (ADCC), as well as upon antigen presentation, was determined using a 51Cr-release assay and [3H]thymidine-uptake of T cells after co-incubation with tetanus-toxoid-pulsed antigen-presenting cells. RESULTS: In patients with early breast cancer, serum levels of sICAM-1 were significantly lower compared to patients with metastatic disease, but did not correlate with usual clinical parameters. In patients with metastatic breast cancer, a significant correlation of sICAM-1 with tumour markers CEA and CA 15-3 was observed. No influence of sICAM-1 upon unspecific cytotoxicity, ADCC, or the ability to present antigen was observed. DISCUSSION: The origin of sICAM-1 in the sera of patients with breast cancer remains unknown. In contrast to its membrane-bound isoform, sICAM-1 was increased in the sera of patients with various stages of breast cancer, but its presence did not influence unspecific cytotoxicity, ADCC, or antigen-induced T cell proliferation.

Detection of minimal residual disease in patients with cancer: a review of techniques, clinical implications, and emerging therapeutic consequences.

The issue of minimal residual disease (MRD) manifesting itself by the presence of undetected disseminated isolated tumor cells in both tissues and hematopoietic autografts from patients with early-stage malignancies or from patients in clinical complete remission has been discussed widely during the last decade. Based on the current understanding of the pathogenesis of malignancy, disseminated tumor cells persisting after conventional oncologic treatment modalities or after reinfusion of contaminated autologous hematopoietic cells constitute the source of subsequent recurrence of disease. Accordingly, much emphasis is placed on the detection and characterization of disseminated isolated tumor cells in both basic and clinical research. This effort is aimed at a better understanding of the processes of metastasis and tumor dormancy and, ultimately, the estimation of prognosis, molecular monitoring, and the design of new therapeutic agents in oncology. In our review, we used computerized (MEDLINE, Embase) and manual searches to summarize laboratory and clinical data concerning MRD focusing on the issue of MRD in solid malignancies. We give a detailed overview of the methods used for the detection and molecular characterization of disseminated tumor cells and of the prevalence and prognostic significance of the detection of MRD in patients and hematopoietic autografts. Finally, we discuss the emerging therapeutic consequences of the detection of disseminated tumor cells, with special emphasis on the therapeutic potential of antibodies. We conclude that the detection of MRD represents a hallmark for the diagnosis, monitoring, and treatment of malignant conditions in future clinical trials.

Phase II study of second-line oxaliplatin, irinotecan and mitomycin C in patients with advanced or metastatic colorectal cancer.

The aim of this phase II study was to investigate the therapeutic value of second-line treatment with oxaliplatin, irinotecan (CPT-11) and mitomycin C (MMC) in patients with metastatic colorectal cancer pretreated with 5-fluorouracil (5-FU)-based chemotherapy. A total of 10 patients with metastatic colorectal cancer, all of whom had developed progressive disease from advanced or metastatic colorectal cancer while receiving or within 6 months after discontinuing first-line chemotherapy with 5-FU and leucovorin, were entered in this study. At the time of relapse, cytotoxic chemotherapy consisting of oxaliplatin 80 mg/m2 plus CPT-11 80 mg/m2 given i.v. on therapeutic day 1, and MMC 6 mg/ m2 given i.v. on day 15, respectively, was initiated. Treatment courses were repeated every 4 weeks for a total of six courses unless there was prior evidence of progressive disease. The overall response rate was 30% with three partial responses for all 10 assessable patients. Two additional patients (20%) had stable disease and five patients (50%) progressed. The median overall survival duration has not been reached yet and is longer than 7.1 months (range 2-23.5+) from the beginning of second-line therapy. Four patients are currently alive with progressive disease. The tolerance of second-line treatment was generally mild to moderate and easy to treat. Our data suggest that the combination of oxaliplatin, CPT-11 and MMC in patients with metastatic colorectal cancer pretreated with 5-FU-based chemotherapy is feasible and has substantial antitumor activity. Further evaluation of this regimen seems warranted.

Sequential administration of interferon gamma and interleukin-2 in metastatic renal cell carcinoma: results of a phase II trial. Austrian Renal Cell Carcinoma Study Group.

BACKGROUND: Because of the known efficacy of several cytokines in the treatment of advanced renal cell cancer (RCC), we have conducted a phase II trial of the efficacy and toxicity of subcutaneous interferon gamma (IFNgamma) and interleukin-2 (IL-2). METHODS: 63 patients with progressive metastatic RCC were treated with 100 microg recombinant IFNgamma1b administered three times weekly during weeks 1 and 2 and with 4.5 MU recombinant IL-2 administered on 4 consecutive days during weeks 3 and 4, every 6 weeks. RESULTS: 11% of patients had an objective response (CR: 3%, PR: 8%), 33% had SD. Toxicity was generally mild. The median duration of remissions (CR + PR) was 9.6 months; the median duration of SD 8 months. A significant survival benefit was evident at a median observation time of 51 months for patients (44%) responding to therapy (P < 0.0001). CONCLUSIONS: we conclude that sequential treatment with IFNgamma and IL-2 may prolong survival in patients with metastatic RCC responding to therapy.

Defective antigen presentation resulting from impaired expression of costimulatory molecules in breast cancer.

Previous experiments from our laboratory have shown that immune mechanisms aiming at the destruction of tumour cells including the recognition of target cells and their elimination via the expression of intercellular adhesion molecule-1 (ICAM-1; CD54), the production of tumour necrosis factor-alpha (TNF-alpha) by monocytes and appropriate function of lymphocyte subpopulations were defective in breast cancer. Previous observations were extended to assess expression levels and regulatory mechanisms of costimulatory molecules CD54, CD80 and CD86 on monocytes derived from patients with early breast cancer (EBC). In addition, antigen presentation by antigen-presenting cells (APC) was analyzed within this context. We report that monocytes derived from patients with EBC exhibited significantly decreased expression levels of CD54 (p = 0.0002), CD80 (p = 0.009) and CD 86 (p = 0.002) compared with monocytes derived from healthy females. Simultaneously, lipopolysaccharide (LPS)-induced TNF-alpha production of monocytes was found to be defective in patients with EBC. Finally, T-cell proliferation in response to tetanus toxoid (TT) was significantly decreased in patients with EBC compared with healthy control females (p < 0.0001). Furthermore, T-cell proliferation in response to TT-pulsed APC derived from healthy controls was significantly inhibited in the presence of anti-CD54 and/or anti-CD80 antibodies in a dose-dependent manner, thus corroborating the necessity of the presence of CD54 and CD80 as costimulatory molecules in the present setting. We conclude that monocytes derived from patients with EBC showed a simultaneous defect of expression of CD54 and its regulation via TNF-alpha, CD80 and CD86 as well as T-cell proliferation following exposure to TT-pulsed APC. Based upon these findings, it is speculated that defects in costimulatory molecule expression might contribute to tolerance of the immune system towards the presence of malignant cells in patients with EBC.

A hypersensitive estrogen receptor-alpha mutation in premalignant breast lesions.

The best current model of breast cancer evolution suggests that most cancers arise from certain premalignant lesions. We have identified a common (34%) somatic mutation in the estrogen receptor (ER)-alpha gene in a series of 59 typical hyperplasias, a type of early premalignant breast lesion. The mutation, which affects the border of the hinge and hormone binding domains of ER-alpha, showed increased sensitivity to estrogen as compared with wild-type ER-alpha in stably transfected breast cancer cells, including markedly increased proliferation at subphysiological levels of estrogen. The mutated ER-alpha exhibits enhanced binding to the TIF-2 coactivator at low levels of hormone, which may partially explain its increased estrogen responsiveness. These data suggest that this mutation may promote or accelerate the development of cancer from premalignant breast lesions.

Monotherapy with docetaxel in second- or third-line treatment of anthracycline-resistant metastatic breast cancer.

Nineteen breast cancer patients pretreated with one or two anthracycline-containing regimens for visceral metastases received i.v. docetaxel 100 mg/m2 on day 1, q 21d. Docetaxel was administered as second-line therapy in 11 patients, whereas eight patients received docetaxel in a third-line setting. In the second-line setting, complete response (CR) was achieved in two (18%), partial response (PR) in four (36%) and stable disease (SD) in three (27%) patients resulting in a response rate (RR) of 54%. In the third-line setting three (38%) patients experienced PR (RR 38%) and two (25%) SD. In the second-line setting, median time to progression was 6.5+/-3.9 months (range 2.1-15.8) versus 4.7+/-5.5 months (range 0.6-15.9) in the third-line setting. Median overall survival was 9.6+/-8.0 months (range 2.7-25.8) versus 11.2-6.1 months (range 4.8-18.7). Overall, no patient experienced treatment-limiting toxicities. We conclude that docetaxel induced responses in 48% of anthracycline-resistant patients enrolled into the present study. The safety profile of docetaxel was manageable and tolerable. Docetaxel represented efficacious treatment in patients with metastatic breast cancer progressing despite previous anthracycline-containing chemotherapy.

Transient increase in mitogen-induced lymphoproliferative responses in patients with testicular cancer after BEP chemotherapy.

OBJECTIVES: To investigate the impact of polychemotherapy on cellular immunity in patients with testicular cancer. METHODS: Lymphocyte subpopulations, lymphoproliferative responses to mitogenic stimulation, and mitogen-induced release of soluble interleukin-2 receptor from peripheral blood mononuclear cells were investigated in 15 patients with testicular germ cell tumors a median of 61 months (range 7 to 73) after polychemotherapy with bleomycin, etoposide, and cisplatin (BEP). RESULTS: The numbers of peripheral blood T cells (CD3+), CD4+ and CD8+ subsets, and lymphoproliferative responses to pokeweed mitogen, phytohemagglutinin, and concanavalin A in patients were comparable to those of healthy control subjects. When two groups of patients were formed according to elapsed time from BEP polychemotherapy and study onset (group A, 12 months and group B, 69 months after termination of BEP), a significant increase in lymphoproliferative response to concanavalin A (P <0.05) was found in group A 1 year after chemotherapy. CONCLUSIONS: BEP chemotherapy administered to patients with testicular cancer does not result in impairment of cellular immunity but rather leads to a significant increase in the capacity of patients' lymphocytes to respond to mitogenic stimulation up to 1 year after polychemotherapy. Moreover, the increased T-cell activity found after BEP therapy may contribute to the high rate of long-term complete remission.

Treatment of extra-abdominal desmoid tumors with interferon-alpha with or without tretinoin.

BACKGROUND AND OBJECTIVES: Surgery is the main treatment for extra-abdominal desmoid tumors, but the results of further management remain uncertain. Therefore, a retrospective analysis was undertaken to evaluate the toxicity and efficacy of treatment with interferon-alpha (IFN-alpha) +/- tretinoin in this setting. METHODS: Thirteen patients with extra-abdominal desmoid tumors and a median age of 32 years (range, 15-73) received IFN-alpha. Seven of these patients received a combination of IFN-alpha and tretinoin in order to test further enhancement. RESULTS: After a mean observation period of 27 +/- 15 months (mean +/- standard deviation) under treatment with IFN-alpha +/- tretinoin, local control was seen in 11 of 13 patients (85%). Seven patients had no evidence of disease at a mean disease-free interval of 22 +/- 18 months; in two patients progressive disease occurred after only 7 and 9 months, respectively, of observation. In another four patients, progression of the desmoid tumor was stabilized. CONCLUSIONS: The data of this retrospective, nonrandomized study on therapy with IFN-alpha +/- tretinoin suggest that such treatment may be effective in prolonging the disease-free interval of patients after intralesional or marginal surgery. Because of the encouraging response rate, this regimen appears to be another nonsurgical treatment alternative.