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1.
Ann Oncol ; 17(10): 1592-7, 2006 Oct.
Article in English | MEDLINE | ID: mdl-17005632

ABSTRACT

BACKGROUND: Temozolomide has shown some efficacy in metastatic melanoma and recently received extended approval to treat brain tumours. The purpose of this study was to test a dose-intensified regimen of temozolomide in melanoma patients with brain metastases in a prospective, open-label, multicentre phase II trial. PATIENTS AND METHODS: Forty-five patients with asymptomatic brain metastases from melanoma were stratified into arm A (no prior chemotherapy; n = 21) and arm B (previous chemotherapy; n = 24). Patients received oral temozolomide either 150 mg/m(2)/day (arm A) or 125 mg/m(2)/day (arm B), days 1-7 and 15-21, every 28 days. The primary study end point was objective response, and secondary end points were overall survival and safety. RESULTS: Two patients (4.4%) achieved a partial response (PR) in brain metastases (one in each arm), one of them (2.2%) also showing a PR in extracerebral disease. An additional five patients (11.1%; two in arm A, three in arm B) showed disease stabilisation (SD) in brain and other sites. However, 82% revealed progressive disease (PD) already evident 8 weeks after therapy initiation. Median survival time from therapy onset was 3.5 months (range 0.7-8.3; arm B) and 4.3 months (range 1.6-11.8; arm A), P = 0.43. Dose modifications and prolongations of therapy cycles due to toxicity were required in 20% of patients. Grade 3/4 toxicity was observed in one patient only (2.2%). CONCLUSIONS: Oral administration of temozolomide given bi-weekly is well-tolerated in melanoma patients with cerebral involvement. However, the efficacy is limited, with lower than 5% objective responses observed in brain and extracerebral metastases.


Subject(s)
Brain Neoplasms/drug therapy , Brain Neoplasms/secondary , Dacarbazine/analogs & derivatives , Melanoma/drug therapy , Skin Neoplasms/drug therapy , Adult , Aged , Antineoplastic Agents, Alkylating/administration & dosage , Antineoplastic Agents, Alkylating/adverse effects , Brain Neoplasms/mortality , Dacarbazine/administration & dosage , Dacarbazine/adverse effects , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Humans , Male , Melanoma/mortality , Melanoma/pathology , Middle Aged , Skin Neoplasms/mortality , Skin Neoplasms/pathology , Survival Analysis , Temozolomide , Treatment Outcome
3.
Onkologie ; 27(6): 540-4, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15591712

ABSTRACT

BACKGROUND: Stage IV melanoma has a poor prognosis with a median survival of 3-11 months from diagnosis of distant metastases. Response rates in first-line regimens range around 15-20%. Non-responders have a median survival around 6 months. Currently, no second-line treatment in advanced melanoma has been established. PATIENTS AND METHODS: In a clinical phase II study we evaluated the efficacy of liposomal doxorubicin (Caelyx) in 30 patients (17 m, 13 f) with progressing metastatic melanoma who had failed a previous chemotherapy. Liposomal doxorubicin was given in an outpatient setting at a dose of 50 mg/m2 i.v. on d1, d22, d43 and d64, subsequently at 40 mg/m2 at d85 before first staging and in 4-week intervals thereafter. Treatment was very well tolerated with 100 cycles given in total. Response rate, survival time, time-to-progression and toxicity were assessed. RESULTS: Erythrodysesthesia was the most severe toxicity in 6% at CTC grade 3. Liposomal doxorubicin was of limited clinical efficacy with 21 patients progressing within the first 12 weeks. However, 7 patients were treated 3-9 months and were stable for >90 days, achieving 5 SD, 1 PR and 1 CR. Median survival after initiation of second-line treatment was 214 days (95% CI: 151-304 days) with 7 patients surviving >300 and 5 patients >400 days. CONCLUSIONS: Liposomal doxorubin as monotherapy is well tolerated but of limited clinical efficacy. Whether the survival benefit of a significant proportion of patients (20%) holds true in larger cohorts and whether the efficacy of liposomal doxorubicin can be improved by combinations without compromising the low toxicity profile needs further studies.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Doxorubicin/administration & dosage , Melanoma/drug therapy , Melanoma/mortality , Neoplasms, Unknown Primary/drug therapy , Neoplasms, Unknown Primary/mortality , Risk Assessment/methods , Adult , Aged , Antineoplastic Agents/administration & dosage , Comorbidity , Drug Administration Schedule , Female , Germany/epidemiology , Hematologic Diseases/epidemiology , Humans , Male , Melanoma/secondary , Middle Aged , Palliative Care/methods , Polyethylene Glycols , Risk Factors , Survival Analysis , Treatment Outcome
4.
Onkologie ; 27(5): 492-9, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15585982

ABSTRACT

Extracutaneous malignant melanomas (EMM) require special consideration in the field of oncology due to their rareness and--depending on the localization--the frequency of late diagnosis with consecutive poor prognosis. Only 4-5% of all primary melanomas do not arise from the skin. Most frequently they originate from the mucous membranes lining the respiratory, digestive, and genitourinary tracts or in the eyes as well as in the cerebral meninges. Extracutaneous melanomas are considered to be biologically more aggressive than cutaneous melanomas. The Clark level and Breslow index used for evaluation of cutaneous melanomas are not applicable to EMM and, at present, there are no consistent, internationally accepted therapy standards for this form of the disease. For this reason, this review focuses primarily on the literature pertaining to therapeutic strategies as well as epidemiologic, biological, and diagnostic aspects of this disease.


Subject(s)
Choroid Neoplasms/therapy , Gastrointestinal Neoplasms/therapy , Head and Neck Neoplasms/therapy , Melanoma/therapy , Meningeal Neoplasms/therapy , Mucous Membrane/pathology , Urogenital Neoplasms/therapy , Choroid Neoplasms/diagnosis , Clinical Trials as Topic , Gastrointestinal Neoplasms/diagnosis , Head and Neck Neoplasms/diagnosis , Humans , Melanoma/classification , Melanoma/diagnosis , Meningeal Neoplasms/diagnosis , Practice Patterns, Physicians' , Skin Neoplasms/diagnosis , Skin Neoplasms/therapy , Urogenital Neoplasms/diagnosis
5.
Environ Toxicol ; 17(3): 203-10, 2002.
Article in English | MEDLINE | ID: mdl-12112628

ABSTRACT

Indoor VOC (volatile organic compound) exposure has been shown to be correlated with airway symptoms and allergic manifestations in children. An investigation was conducted within an ongoing birth cohort study (LISA: Lifestyle-Immune System-Allergy) of the association between maternal exposure to VOCs and immune status at birth, in particular the cytokine secretion profile of cord-blood T cells. In a randomly selected group of 85 neonates, cytokine-producing cord-blood T cells were analyzed using intracellular cytokine detection. VOC exposure was measured in children's dwellings by passive sampling, while parents were asked to complete questionnaires about possible sources of VOC exposure. Adjusted odds ratios (ORs) were calculated by logistic regression based on categorized quartiles. A positive association was found between elevated percentages of interleukin-4-producing (IL-4) type 2 T cells and exposure to naphthalene (OR = 2.9) and methylcyclopentane (OR = 3.3). Exposure to tetrachloroethylene was associated with reduced percentages of interferon-gamma-producing (IFN-gamma) type 1 T cells (OR = 2.9). In addition, smoking during pregnancy was correlated with a higher indoor air concentration of naphthalene (OR = 3.8), new carpets in infants' bedrooms with elevated methylcyclopentane concentrations (OR = 4.1), and home renovation with a higher trichloroethylene burden (OR = 4.9). Our data suggest that maternal exposure to VOC may have an influence on the immune status of the newborn child.


Subject(s)
Air Pollution, Indoor/adverse effects , Carcinogens/adverse effects , Hypersensitivity/etiology , Maternal Exposure , Naphthalenes/adverse effects , T-Lymphocytes/drug effects , Tetrachloroethylene/adverse effects , Adult , Cohort Studies , Cytokines/metabolism , Female , Humans , Infant, Newborn , Odds Ratio , Pregnancy , Regression Analysis , T-Lymphocytes/physiology , Volatilization
6.
Allergy ; 57(2): 129-36, 2002 Feb.
Article in English | MEDLINE | ID: mdl-11929415

ABSTRACT

BACKGROUND: Within an ongoing birth cohort study (LISA) the cytokine production of cord blood T cells was compared between neonates from Leipzig (East Germany) and Munich (West Germany). The aim of this study was to analyse regional differences and influencing factors of the immune status. METHODS: Cytokine production was measured in a randomly selected subgroup of 158 children from the LISA (Life style - Immune system - Allergy) cohort by intracellular cytokine staining. Information on family "atopy" history (FAH) and home characteristics was obtained from questionnaires. RESULTS: Reduced numbers of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) producing T cells were found in association with biparental FAH and housing renovation during pregnancy. In addition, cytokine production was influenced by season. In Munich, the frequency of biparental FAH and of renovation measures during pregnancy was significantly higher as compared to Leipzig. Neonates from Munich showed significantly decreased amounts of IFN-gamma and TNF-alpha and elevated levels of interleukin-4 (IL-4) producing T cells. Differences in cytokine production between Munich and Leipzig were influenced by season (IL-4) and housing renovation (IFN-gamma, TNF-alpha). CONCLUSIONS: Since differences in the T cell cytokine production of neonates in Munich and Leipzig are independent from FAH our findings may provide evidence for the impact of environmental factors upon the fetal immune system.


Subject(s)
Infant, Newborn/immunology , T-Lymphocytes/immunology , Cohort Studies , Cytokines/biosynthesis , Cytokines/blood , Cytokines/immunology , False Positive Reactions , Family Health , Female , Fetal Blood/cytology , Fetal Blood/immunology , Genetic Predisposition to Disease , Germany, East/epidemiology , Germany, West/epidemiology , Humans , Hypersensitivity, Immediate/diagnosis , Hypersensitivity, Immediate/genetics , Hypersensitivity, Immediate/immunology , Immunoglobulin E/blood , Immunoglobulin E/immunology , Infant Welfare , Male , Maternal Welfare , Pregnancy , Prospective Studies , Random Allocation , Surveys and Questionnaires
7.
Neurol Neurochir Pol ; 28(2): 189-94, 1994.
Article in Polish | MEDLINE | ID: mdl-8047229

ABSTRACT

112 case of ALS in the Province of Lódz diagnosed between 1980-1986 are analysed. The male: female ratio was 1.5:1. The median age at onset was 54.8. The peak incidence of ALS was in the age group 51-60. The average annual incidence of ALS was 1.8/100,000. The prevalence in December 31, 1986 was 4.5 per 100,000. The median survival time after the onset of the disease was 30.12 months. The results show no history of exposure to heavy metals and occupation. More case of ALS than expected were found in urban areas. The ALS patients significantly more often gave histories of trauma of the limbs and contact with dogs.


Subject(s)
Amyotrophic Lateral Sclerosis/epidemiology , Spinal Cord/physiopathology , Adult , Age Factors , Aged , Amyotrophic Lateral Sclerosis/diagnosis , Amyotrophic Lateral Sclerosis/physiopathology , Animals , Blood Proteins , Dogs , Extremities/injuries , Female , Humans , Male , Poland/epidemiology , Sex Factors , Urban Population
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