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Stable Disease (stable + disease)
Selected AbstractsA lower dose of thalidomide is better than a high dose in metastatic renal cell carcinomaBJU INTERNATIONAL, Issue 4 2005Sandy Srinivas OBJECTIVE To conduct a dose-finding trial using a single low dose and dose escalation of a higher dose of thalidomide in patients with metastatic renal cell carcinoma (RCC), and to evaluate the antineoplastic effectiveness of thalidomide as an anti-angiogenic agent on RCC. PATIENTS AND METHODS The 14 patients enrolled in the study had progressive measurable metastatic RCC and consented to participate. Patients were randomized to either a fixed low dose of 200 mg of thalidomide or to a high dose of 800 mg that was increased to a maximum dose of 1200 mg daily. Patients were evaluated for response after 8 weeks of therapy. RESULTS Stable disease was achieved in six patients and was seen in both the low-dose and high-dose thalidomide groups. The median overall survival was 9 months. The low-dose thalidomide regimen was better tolerated and patients survived longer than those on the high-dose regimen (16 vs 6 months, P = 0.04) CONCLUSION The use of low-dose thalidomide in patients with metastatic RCC was well tolerated and they survived for longer than those on the high-dose regimen. [source] Routine clinical use of alemtuzumab in patients with heavily pretreated B-cell chronic lymphocytic leukemia,,CANCER, Issue 10 2006A nation-wide retrospective study in Austria Abstract BACKGROUND. In previous studies, alemtuzumab demonstrated considerable activity in patients with previously treated B-cell chronic lymphocytic leukemia (CLL), including fludarabine-refractory disease. In this retrospective study, the authors evaluated the benefit of alemtuzumab monotherapy in unselected patients with advanced, previously treated CLL who received treatment in the routine clinical setting. METHODS. Data were collected from 115 consecutive patients who received alemtuzumab therapy at 25 participating centers in Austria. Patients received a median of 3 prior lines of therapy (range, 1,11 prior lines of therapy), and 59% had fludarabine-refractory disease. Alemtuzumab was administered intravenously or subcutaneously with a planned schedule of 30 mg 3 times per week for up to 12 weeks. Patients received valacyclovir and trimethoprim/sulfamethoxazole for antiinfective prophylaxis. RESULTS. The overall response rate was 23%, with complete responses achieved in 5% of patients. Stable disease (SD) was achieved in 36% of patients. After a median follow-up of 17.5 months, the median overall survival (OS) was 20.2 months for all patients. A multivariate Cox regression analysis that included pretreatment baseline characteristics, response to therapy, and cumulative dose of alemtuzumab indicated that bulky lymphadenopathy, the administration of ,3 previous therapies, and lack of response to alemtuzumab remained significant independent risk factors for inferior OS. The median OS had not been reached for responding patients. The median OS was 29.5 months for patients with SD and 10.8 months for patients with progressive disease. CONCLUSIONS. The broad use of alemtuzumab in the routine clinical practice setting is feasible and active in unselected patients with pretreated CLL, and the current results confirmed the activity and safety of this agent, as reported in previously published clinical studies. Cancer 2006. © 2006 American Cancer Society. [source] A Phase II study of gemcitabine and cisplatin in advanced biliary tract cancerCANCER, Issue 6 2006Seung Tai Kim M.D. Abstract BACKGROUND The authors performed a Phase II study of combination chemotherapy with gemcitabine and cisplatin in patients with inoperable biliary tract cancer to evaluate efficacy and toxicity of this combination. In addition, the correlation between the CA 19-9 response and clinical outcome was analyzed. METHODS The eligibility criteria for this study were 1) histologically or cytologically confirmed inoperable biliary tract cancer in patients with metastatic or recurrent disease; 2) age between 18 and 70 years; 3) at least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria; 4) an Eastern Cooperative Oncology Group (ECOG) performance status , 2; 5) a life expectancy of at least 3 mos; and 6) adequate bone marrow, hepatic, and renal function. The patients received gemcitabine (1250 mg/m2, Days 1 and 8) and cisplatin (60 mg/m2, Day 1) every 3 weeks. Tumor response was assessed by RECIST criteria every 2 cycles of chemotherapy. Treatment was continued until progression of disease was documented. RESULTS Twenty-nine patients were enrolled. The median age of these patients was 52 years (range, 37 to 69 yrs), and the median ECOG performance status was 1. No complete response was observed, and 10 of 29 patients had partial responses. The overall response rate was 34.5% (95% confidence interval [CI], 17.9,54.3) for the intent-to-treat analysis. Stable disease was observed in 4 (13.8%) patients and progressive disease in 13 (44.8%) patients. The median follow-up time was 10.0 months (95% CI, 7.2,12.8). The median time to progression (TTP) was 3.0 months (95% CI, 2.12,3.88), and the median overall survival was 11 months (95% CI, 5.49,16.5). Although these results showed a better response rate (57.1 % vs. 27.3%) and survival (12 vs. 10 mos) in patients with a decline in CA 19-9 of at least 25%, these data were statistically not significant. In addition, there was a significant positive correlation between the increment in CA 19-9 values and tumor progression as determined with RECIST criteria (r = 0.96, P < 0.01). However, there was no definite correlation between the CA 19-9 response and the response according to RECIST criteria (P = 0.087). National Cancer Institute (NCI) common toxicity criteria (CTC) Grade 3 or 4 hematologic toxicities included neutropenia in 4 (14%) patients and anemia in 1 (3%) patient. Two of 4 patients with Grade 3 or 4 neutropenia had febrile episodes (7%) and required hospital admissions. NCI-CTC Grade 3 or 4 nonhematologic toxicity included nausea in 1 (3%) patient. There were no treatment-related deaths. CONCLUSION The combination chemotherapy with gemcitabine and cisplatin in inoperable biliary tract cancer was tolerable for most patients and showed modest response rates. The role of CA 19-9 monitoring as a surrogate biomarker in patients with BTC treated with gemcitabine chemotherapy should be further investigated. Cancer 2006. © 2006 American Cancer Society. [source] Effect of Perilesional Injections of PEG-Interleukin-2 on Basal Cell CarcinomaDERMATOLOGIC SURGERY, Issue 11 2000Baruch Kaplan MD Background: Multiple modalities are available for the treatment of basal cell carcinoma (BCC). The most commonly used modalities include simple excision, Mohs micrographic surgery, curettage and electrodessication, cryosurgery, and irradiation therapy. Interleukin-2 (IL-2) is a cytokine produced chiefly by activated T lymphocytes and has effects on various components of the immune system. Until now the primary clinical use of IL-2 has been in advanced stages of metastatic melanoma and renal cell carcinoma. Systemic administration of IL-2 is known to cause significant toxicity. Objective: The objective of this study was to evaluate the therapeutic efficacy and safety of perilesional PEG-IL-2 injections in patients with BCC in an open label, uncontrolled pilot study. Methods: Patients with histologically confirmed primary BCC over 18 years of age were included in the study. Lesions were treated by injecting a total volume of 0.5 cc of IL-2 in a radial fashion in the subcutaneous tissue. Injection dosages ranged from 3000 to 1,200,000 IU in one to four weekly dosages. A total of 12 tumors were treated in eight patients. Results: Overall response rates were as follows: complete response in 8 of 12 treated tumors (66.6% cure rate), partial response in 3 of 12 injected tumors (25% partial response rate), stable disease with no improvement in 1 treatment site (8.4%). Side effects included local pain, swelling, and erythema, and in one patient flulike symptoms. There were no significant changes of blood tests as compared to baseline levels. Conclusions: The therapeutic response induced by perilesional PEG-IL-2 injections was found to be an encouraging, safe, and well-tolerated treatment of BCC. Further studies including a larger patient population and long-term follow-up are necessary in order to substantiate these findings. [source] Preoperative chemoradiotherapy in cancer of the thoracic esophagusDISEASES OF THE ESOPHAGUS, Issue 1 2003G. Terrosu SUMMARY. Surgery with or without adjuvant radiotherapy (RT) is the standard treatment of esophageal cancer. Preoperative radio- and chemotherapy (CT) have been introduced to improve prognosis. We report a phase II prospective non-randomized trial of preoperative RT (42 Gy/25) plus CT (cisplatin 20 mg/mq/day plus 5-fluorouracil 600 mg/mq/day, 1,5 weeks) for the treatment of thoracic esophageal cancer. From 1993, 50 patients were enrolled (40 men and 10 women, mean age 57 years, range 30,75 years). Squamous cell carcinoma accounted for 90% of cases; 10% were adenocarcinoma. Downstaging of the disease was obtained in 77.3% of cases; there were 13 (29.5%) complete responses (CR) and 21 (47.7%) partial responses (PR). Median survival was 28 and 25 months, respectively, for CR and partial response (PR) plus stable disease (SD) and progressive disease (PD) (P = 0.05). Progressive-free median survival was 22 and 17 months, respectively, for CR and PR + SD + PD (P = 0.08). Multimodal treatment of esophageal cancer showed promising results, although not significant, in terms of survival and disease progression for patients achieving a complete pathologic response. [source] Assessment of the predictive value of clinical and histopathological factors as well as the immunoexpression of p53 and bcl-2 proteins in response to preoperative chemotherapy for esophageal squamous cell carcinomaDISEASES OF THE ESOPHAGUS, Issue 3 2000J. Szumilo The aim of the study was to determine the predictive value of selected clinical and histopathological factors as well as the immunohistochemical expression of p53 and bcl-2 proteins in the prediction of the pathological response to preoperative chemotherapy in esophageal squamous cell carcinoma. Thirty-four patients with advanced squamous cell carcinoma of the thoracic esophagus (T2,4 N0,1 M0), who underwent one cycle of cisplatin and 5-fluorouracil therapy followed by subtotal esophagectomy, were studied. All clinical factors (tumor longitudinal diameter in a computed tomographic scan, invasion depth, the presence of lymph node metastasis and clinical tumor staging) were evaluated before the onset of the therapy. The histopathological features (grade of differentiation, degree of keratinization, nuclear polymorphism, mitotic index, pattern of cancer invasion and inflammatory response), and the expression of p53 and bcl-2 proteins were also estimated in prechemotherapy endoscopic biopsy specimens. Pathological response to chemotherapy was assessed in surgically resected specimens. Of 34 patients, two (5.9%) showed complete response (CR), six patients (17.6%) exhibited major histological changes (partial response 1; PR1), 24 (70.6%) showed minor histological changes (partial response 2; PR2), and two patients (5.9%) exhibited no response to chemotherapy (stable disease; SD). There were no significant relationships between the response to preoperative chemotherapy (CR + PR1 vs. PR2 + SD) and the majority of the clinical and all the histopathological features. Deeper cancer invasion before chemotherapy was the only factor that tended to worsen the therapy effect (p < 0.01). The pathological response to treatment had no significant associations with the expression of p53 and bcl-2 proteins in esophageal squamous cell carcinoma. It should be noted, however, that both patients in CR were p53 and bcl-2 protein-negative. [source] Human immunodeficiency virus-associated diffuse non-Hodgkin's lymphoma in Venezuelan patients: treatment with full-dose cyclophosphamide-doxorubicin-vincristine-prednisone without routine use of granulocyte-colony stimulating factorEUROPEAN JOURNAL OF CANCER CARE, Issue 5 2006D.E. HERNÀNDEZ md, phd The routine use of granulocyte-colony stimulating factor (G-CSF) for 10 days during full-dose cyclophosphamide-doxorubicin-vincristine-prednisone (CHOP) chemotherapy in HIV-associated diffuse non-Hodgkin's lymphoma (NHL) patients is very expensive in developing countries. We treated 22 HIV-associated diffuse NHL patients with standard-dose CHOP and used G-CSF after an episode of febrile neutropenia until neutrophil count reached 1000/mm3. The clinical response was: complete response (36%), partial response (32%), stable disease (14%) and progression (18%). There were no toxicity-related deaths. Grade 3 or 4 neutropenia was observed in 16% of cycles, but only 8% were complicated with febrile neutropenia. Seventeen patients died (median survival 15 months; range 2,70). There are five patients alive (median survival 24+ months; range 17,36+). Our experience showed that we can treat HIV-related NHL patients with full-dose CHOP, achieve good responses and have an acceptable toxicity profile, with the use of G-CSF as needed. [source] Ifosfamide, etoposide, cytarabine, and dexamethasone as salvage treatment followed by high-dose cyclophosphamide, melphalan, and etoposide with autologous peripheral blood stem cell transplantation for relapsed or refractory lymphomasEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 2 2007P. Schütt Abstract High-dose chemotherapy (HD-CT) with autologous stem cell transplantation is considered to be the treatment of choice for relapsed high-grade non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL) patients, but the optimal treatment has not yet been defined. We evaluated a salvage treatment regimen consisting of conventional cycles with ifosfamide, etoposide, cytarabine, and dexamethasone (IVAD) followed by two cycles of HD-CT consisting of cyclophosphamide, melphalan, and etoposide (CMV) with autologous stem cell support in patients with relapsed or refractory NHL (n = 59) and HL (n = 16). Response to IVAD was complete remission (CR) in 16 patients (21%), partial remission (PR) in 39 patients (52%), stable disease (SD) in 18 patients (24%), and progressive disease (PD) in two patients (2.7%). Of 70 patients treated with HD-CT, 41 patients (59%) showed a CR, 20 patients a PR (29%), eight patients a SD (11%), and one patient a PD (1.4%). The 5-yr overall survival for the entire group of patients was 29%, and for patients with NHL and HL 25%, and 38%, respectively. The respective event-free survival probabilities at 5 yr were 22%, 16%, and 31%. Seven treatment-related deaths due to septicemia (three), cardiac arrhythmia (one), pneumonia (one), pneumonitis (one), and toxic epidermal necrolysis (one) were observed. In multivariate analysis, an International Prognostic Index of ,2 and resistant disease to first-line chemotherapy were poor independent prognostic factors for the subgroup of patients with NHL. In conclusion, these results indicate that IVAD/CMV is feasible as a salvage therapy for lymphoma patients. This treatment is currently evaluated with the addition of rituximab. [source] Absence of veno-occlussive disease in a cohort of multiple myeloma patients undergoing autologous stem cell transplantation with targeted busulfan dosageEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2006A. Clopés Abstract:,Background:,Plasma concentrations of oral busulfan (BU) were measured in multiple myeloma (MM) patients undergoing autologous peripheral blood stem cell transplantation (ASCT) with a double alkylating conditioning protocol in order to individualise doses of BU based on individual pharmacokinetic parameters and to reduce toxicities related to BU exposure. Patients and methods:,Forty-four consecutive patients with MM participating in the co-operative Spanish protocol were prospectively evaluated. Conditioning regimen prior to autologous infusion consisted of BU followed by melphalan. BU pharmacokinetic parameters were estimated for each patient after the first dose based on measured concentrations and subsequent doses were modified as necessary to achieve target exposure. Results:,Mean BU exposure (AUCss) (±DS) before dosage modification range from 3192 to 12 180 ng h/mL. Twenty-six out of 44 (59%) patients required dose adjustment. None of the patients developed hepatic veno-occlusive disease (VOD). Grade , II oropharyngeal mucositis was observed in the majority of patients (95%) and the severity of mucositis increased with increasing average steady-state BU plasma concentration. There were four treatment-related deaths: two patients died from multiorgan failure and two of respiratory infections. Of the remaining 40 patients, 15 were in complete remission with negative immunofixation, 21 in partial remission and four in stable disease 3 months after ASCT. Conclusions:,The results of the present study show the variability in BU pharmacokinetic parameters and suggest the possible relationship between toxicities and BU exposure. Individualising BU dosage in MM patients undergoing ASCT we observed the absence of VOD. [source] Ifosamide, epirubicin and granulocyte colony-stimulating factor: a regimen for successful mobilization of peripheral blood progenitor cells in patients with multiple myelomaHEMATOLOGICAL ONCOLOGY, Issue 2 2001M. Arland Abstract In general, the mobilization of peripheral blood progenitor cells (PBPC) in multiple myeloma (MM) patients is poor and is achieved in most cases by combined cyclophosphamide and G-CSF. This study was performed to examine the efficacy of combined ifosfamide/epirubicine and G-CSF for PBPC mobilization and purging. Sixteen patients suffering from multiple myeloma in stage II/A and III/A according to Durie and Salmon underwent chemotherapy consisting of a total of three cycles of ifosfamide (3,g/m2 on days 1 and 2 and epirubicine 80,mg/m2 on day 1) and G-CSF (10 or 20,µg/kg body weight (BW) daily until harvesting). PBPC harvesting was performed after the first and third cycle of chemotherapy. The median number of PBPC after the first cycle of chemotherapy was 7.79×106 CD34+ cells/kg BW (ranging from 0.94,26.36×106) and 6.38×106 CD34+ cells/kg BW (ranging from 0.79,29.31×106) after the third cycle of chemotherapy. Clinical re-evaluation after three cycles of chemotherapy showed 13 (81 per cent) patients in partial remission (PR), two (12 per cent) in complete remission (CR) and one (6.25 per cent) in stable disease (SD). No major side-effects were observed, six patients developed hematological toxicity stage IV WHO for a median of 3.9 days but no serious infection episodes occurred. Combined ifosfamide/epirubicin and standard G-CSF is able to mobilize sufficient PBPC without serious side-effects for patients with MM and for purging procedures resulting in a high proportion of complete remissions after tandem high-dose melphalan chemotherapy. Copyright © 2001 John Wiley & Sons, Ltd. [source] Immunization with a P53 synthetic long peptide vaccine induces P53-specific immune responses in ovarian cancer patients, a phase II trial,INTERNATIONAL JOURNAL OF CANCER, Issue 9 2009Ninke Leffers Abstract The prognosis of ovarian cancer, the primary cause of death from gynecological malignancies, has only modestly improved over the last decades. Immunotherapy is one of the new treatment modalities explored for this disease. To investigate safety, tolerability, immunogenicity and obtain an impression of clinical activity of a p53 synthetic long peptide (p53-SLP) vaccine, twenty patients with recurrent elevation of CA-125 were included, eighteen of whom were immunized 4 times with 10 overlapping p53-SLP in Montanide ISA51. The first 5 patients were extensively monitored for toxicity, but showed no , grade 3 toxicity, thus accrual was continued. Overall, toxicity was limited to grade 1 and 2, mostly locoregional, inflammatory reactions. IFN-, producing p53-specific T-cell responses were induced in all patients who received all 4 immunizations as measured by IFN-, ELISPOT. An IFN-, secretion assay showed that vaccine-induced p53-specific T-cells were CD4+, produced both Th1 and Th2 cytokines as analyzed by cytokine bead array. Notably, Th2 cytokines dominated the p53-specific response. P53-specific T-cells were present in a biopsy of the last immunization site of at least 9/17 (53%) patients, reflecting the migratory capacity of p53-specific T-cells. As best clinical response, stable disease evaluated by CA-125 levels and CT-scans, was observed in 2/20 (10%) patients, but no relationship was found with vaccine-induced immunity. This study shows that the p53-SLP vaccine is safe, well tolerated and induces p53-specific T-cell responses in ovarian cancer patients. Upcoming trials will focus on improving T helper-1 polarization and clinical efficacy. © 2009 UICC [source] Molecular determinants of irinotecan efficacyINTERNATIONAL JOURNAL OF CANCER, Issue 10 2006Daniel Vallböhmer Abstract Molecular markers predicting the efficacy of CPT-11 based chemotherapies in patients with colorectal cancer (CRC) are unknown. Therefore, we investigated whether mRNA levels of drug targets (Topoisomerase I, TS), enzymes involved in 5-FU metabolism (DPD), in angiogenesis (EGFR, IL-8, VEGF) and in DNA-repair/drug detoxification (ERCC1, GST-P1) are associated with the clinical outcome of patients with CRC treated with first-line CPT-11 based chemotherapy. Thirty three patients with metastatic CRC were included in the study. Intratumoral gene expression levels were assessed from paraffin-embedded tissue samples, using laser capture microdissection and quantitative Real-Time PCR. Complete response was observed in 1 patient, partial response in 12 patients, stable disease in 13 patients and progressive disease in 6 patients. Response was inevaluable for 1 patient. Patients with complete response or partial response were classified as responders, while patients with stable disease or progressive disease were classified as nonresponders. High intratumoral mRNA levels of EGFR, ERCC1 and GSPT-P1 were each significantly associated with response to CPT-11 based chemotherapy. Recursive partitioning analysis showed that mRNA levels of EGFR and ERCC1 are primarily responsible for delineating responders from nonresponders. Also, the combination of high intratumoral gene expression levels of both EGFR and ERCC1 was significantly associated with progression-free survival. The mRNA levels of EGFR had a significant correlation with expression levels of ERCC1, GST-P1 and VEGF. This small retrospective study suggests that gene expression levels of EGFR, ERCC1 and GST-P1 may be useful in predicting the clinical outcome of patients with metastatic CRC treated with first-line CPT-11 based chemotherapy. © 2006 Wiley-Liss, Inc. [source] Gemcitabine and capecitabine chemotherapy in Japanese patients with immunotherapy-resistant renal cell carcinomaINTERNATIONAL JOURNAL OF UROLOGY, Issue 6 2009Norihito Soga Abstract The objective of this study was to evaluate the efficacy and toxicity of combined gemcitabine and capecitabine (Gca) chemotherapy in patients with advanced renal cell cancer after immunotherapy failure. Nine patients were enrolled in this trial. Gemcitabine (1000 mg/m2) was injected on days 1 and 8, followed by oral administration of capecitabine (1660 mg/m2) on days 1,14. The response rate was 11%, with a partial response in one patient (11%), stable disease in five patients (56%) and disease progression in three patients (33%). Grade 3,4 neutropenia was observed in one patient (11%) and thrombocytopenia in two patients (22%). The quality of life (QOL) questionnaire scales showed no significant changes induced by chemotherapy. The median progression-free survival was 4 months with an overall 1-year survival rate of 78%. Gemcitabine and capecitabine chemotherapy can be safely administered as second-line therapy in renal cell cancer patients, maintaining QOL baseline parameters. [source] Immunotherapy against metastatic renal cell carcinoma with mature dendritic cellsINTERNATIONAL JOURNAL OF UROLOGY, Issue 4 2007Akihiko Matsumoto Objective: We performed a clinical trial of immunotherapy using autologous mature dendritic cells (DC) pulsed with autologous tumor lysate, for patients with metastatic renal cell carcinoma (RCC). Methods: Patients with refractory metastatic RCC were enrolled in the study. All of them received interferon (IFN)-, treatment after nephrectomy and were followed over 3 months prior to this study. Autologous monocyte-derived immature DC were pulsed with lysate from autologous primary tumor as the antigen and keyhole limpet hemocyanin (KLH) as immunomodulator, and cultured in the presence of tumor necrosis factor (TNF)-,, interleukin (IL)-1,, and prostaglandin (PG)E2 to generate mature DC. Mature DC were injected intradermally near bilateral inguinal lymph nodes of the patients. A delayed-type hypersensitivity (DTH) test and enzyme-linked immunospot (ELISPOT) assay were performed to evaluate the immunological response. After 4 months from first injection, the clinical effect was evaluated by diagnostic imaging. Results: The treatments were well tolerated without significant toxicity by the patients who were an average of 65.7 years old and had multiple metastases in the lung and other organs. One of the two patients developed a positive DTH reaction to tumor lysate and the other patient only to KLH. The patient with a positive DTH reaction to tumor lysate had stable disease in the clinical evaluation. Conclusions: We confirmed the safety of DC therapy in this clinical trial. The DTH test revealed that the DC therapy induced immunological response to RCC. On the other hand, it was necessary to reconsider the patient selection criteria. [source] Neodymium-YAG Laser for hemangiomas and vascular malformations , long term resultsJOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 6 2005Die Behandlung von Hämangiomen und vaskulären Fehlbildungen mit dem Neodymium-YAG-Laser, Langzeitergebnisse Hämangiom; Lasertherapie; Nd:YAG-Laser; vaskuläre Malformation Summary Background: Hemangiomas and vascular malformations are the most common vascular lesions of infancy. Different lasers can be used for treatment. Nd:YAG laser photocoagulation is particularly effective because of its deep penetration into tissue. Patients and methods: Thirty-one patients, aged from three months to 18,years, with voluminous hemangiomas and venous malformations were treated with a cw-neodymium:YAG laser. The quartz fibre was used in percutaneous and intralesional technique. Long-term follow-up data were acquired by clinical control or a patient questionnaire for a maximal period of eight years. Twenty patients could be evaluated. Results: In the group with hemangiomas (n,=,15), three cases showed nearly complete remission (> 90 %), ten cases had a partial reduction in size (50,,,90 %), in one case there was stable disease and in one case tumor growth. In the group with venous malformations (n,=,5) two cases showed an excellent response (> 90 %), one case a moderate response (25,,,50 %) and in two cases there was no improvement. Adverse effects included scars (40 %), hyper- and hypopigmentation (23 %), mild atrophy (20 %) and a wrinkled texture (17 %). After maximal reduction in size, 30 % of the patients were not satisfied with the laser treatment outcome and elected surgical excision of the residual lesion. Conclusions: The neodymium:yttrium aluminium garnet (Nd:YAG) laser with percutaneous or intralesional application technique is a valuable tool for selected patients with hemangiomas and venous malformations. Zusammenfassung Hintergrund: Hämangiome und vaskuläre Malformationen sind die häufigsten Gefäßfehlbildungen in der Kindheit. Eine Therapieoption stellt die Laserbehandlung dar. Der Nd:YAG-Laser ist besonders effektiv aufgrund seiner hohen Eindringtiefe ins Gewebe. Patienten und Methodik: Insgesamt wurden 31,Patienten im Alter zwischen drei Monaten und achtzehn Jahren mit voluminösen Hämangiomen und venösen Malformationen mit einem cw-Neodymium:YAG-Laser behandelt. Die Laserfaser wurde in perkutaner und intraläsionaler Technik angewendet. Die Nachbeobachtung über einen Zeitraum von maximal acht Jahren erfolgte mittels klinischer Kontrollen oder einem Patientenfragebogen. Von den insgesamt 31,Patienten konnten 20 ausgewertet werden. Ergebnisse: In der Gruppe der Patienten mit Hämangiomen zeigten drei Patienten eine fast vollständige Rückbildung (> 90 %), zehn Patienten eine partielle Rückbildung (50,,,90 %), in einem Fall zeigte sich ein unveränderter Befund und bei einem Patienten beobachteten wir weiterhin Wachstum. In der Gruppe der Patienten mit venösen Malformationen zeigten zwei Patienten ein exzellentes Ansprechen (> 90 %), ein Patient ein moderates Ansprechen (25,,,50 %) und bei zwei Patienten kam es zu keiner Verbesserung. Nebenwirkungen beinhalteten Narben (40 %), Hyper- und Hypopigmentierungen (23 %), geringe Atrophie (20 %) und eine Hautfältelung. Nach vollständiger Rückbildung waren 30 % der Patienten unzufrieden mit dem Ergebnis und unterzogen sich einer operativen Entfernung der Residuen. Schlußfolgerungen: Der Nd:YAG-Laser mit perkutaner und intraläsionaler Applikationstechnik stellt eine wirksame Methode zur Behandlung ausgewählter Patienten mit Hämangiomen und venösen Malformationen dar. [source] Intra-arterial 5-fluorouracil/interferon combination therapy for hepatocellular carcinoma with portal vein tumor thrombosis and extrahepatic metastasesJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 6 2010Yoshio Katamura Abstract Background and Aims:, We investigated the efficacy of intra-arterial 5-fluorouracil (5-FU) and systemic interferon (IFN)-, (5-FU-IFN) in the treatment of hepatocellular carcinoma (HCC) with portal vein tumor thrombosis in the first branch or trunk (Vp3/4) and extrahepatic metastases. Methods:, We examined 17 HCC patients with Vp3/4 and extrahepatic metastases (meta group) and 31 HCC patients with Vp3/4 (non-meta group). Baseline intrahepatic tumor factors and the hepatic reserve were similar between groups. The extrahepatic metastases of the meta group were not considered prognostic factors. Following the administration of 5-FU/IFN to all patients, we compared the survival rates, response, time to progression (TTP), and safety between groups. Results:, For intrahepatic HCC, complete response, partial response, stable disease, progressive disease, and drop out were observed in no (0%), one (6%), seven (41%), nine (53%), and no (0%) patients of the meta group, and in five (16%), seven (23%), 13 (42%), five (16%) and one (3%) patient of the non-meta group, respectively. The response rate was significantly lower in the meta group (6% vs 39%, P = 0.018). The median TTP of intrahepatic HCC and the median survival time were significantly shorter in the meta group than in the non-meta group (1.6 vs 6.3 months, P = 0.0001, and 3.9 months vs 10.5 months, P < 0.0001, respectively). The multivariate analysis showed that the absence of extrahepatic metastases was a significant and independent determinant of both TTP of intrahepatic HCC (P < 0.001) and overall survival (P < 0.001). No patient died of extrahepatic HCC-related disease. Conclusions:, The efficacy of 5-FU/IFN for advanced HCC with Vp3/4 and extrahepatic metastases was markedly limited. [source] Randomized study of preoperative chemotherapy versus primary surgery for stage IB cervical cancerJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 3 2006Hong-Bing Cai Abstract Aim:, To determine the most effective treatment and long-term outcome of patients with stage IB carcinoma of the cervix. Methods:, From January 1999 to December 2001, 106 women with cervical cancer stage IB received neoadjuvant chemotherapy (n = 52) or primary surgery (n = 54). These were randomly assigned. Clinical effects and pathological changes were simultaneously recorded. Results:, The overall clinical response rate was 84.6% and included a complete response (CR) in four patients (7.7%), partial response (PR) in 40 patients (76.9%), and stable disease (SD) in the remaining eight patients (15.4%). Surgery revealed positive nodes in 9.6% neoadjuvant chemotherapy group patients and in 29.6% primary surgery group patients (P = 0.014). Similar results occurred with vascular space involvement: 27.8% in the primary surgery group compared to 9.6% in the neoadjuvant chemotherapy group (P = 0.024). However, parametrial infiltration was found in 7.4% of the patients in the primary surgery group, while only 3.8% showed it in the neoadjuvant chemotherapy group (P = 0.679). The overall 5-year survival rate was significantly higher for all patients who received neoadjuvant chemotherapy (84.6%) than for the control group (75.9%) (P = 0.0112). The median survival time in patients with complete response and partial response to chemotherapy (83.3 months) was significantly higher than that of patients with stable disease to chemotherapy (55.2 months) (P = 0.0049). 27.3% of patients developed recurrent disease within 5 years of the primary treatment. The women with recurrence included partial response in six patients (60.0%), and stable disease in four patients (40.0%). For the other patients there was partial response and complete response in 38 patients (90.5%), and stable disease in the remaining four patients (9.5%) (P = 0.035). Conclusion:, Neoadjuvant chemotherapy can effectively eliminate the pathological risk factors and improve long-term survival in patients with locally advanced cervical cancer. [source] Pilot study: rapamycin in advanced hepatocellular carcinomaALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2010M. Schöniger-Hekele Summary Background, The PI3K/Akt/mTOR signal pathway is involved in hepatocarcinogenesis. Rapamycin (=sirolimus), a specific mTOR inhibitor, leads to G(1) arrest of many malignant cell lines and currently, analogues of rapamycin are being investigated as a cancer chemotherapeutic adjuvant. Aim, To study the toxicity and tolerability of rapamycin therapy in patients with advanced hepatocellular carcinoma (HCC). Methods, Between June 2005 and February 2007, patients with advanced HCC, not eligible for any established therapy, were included in the study. Results, Eighteen patients (F/M: 5/13) with compensated liver cirrhosis (Child A n = 11, Child B n = 5, Child C n = 2) and histologically proven HCC were included in this study. According to the BCLC staging system, most of the patients enrolled had an advanced HCC: BCLC stage B: n = 2, Barcelona Clinic Liver-Cancer (BCLC) stage C: n = 14, BCLC stage D: n = 2. Overall, therapy with rapamycin was well tolerated. Most common toxicities were thrombocytopaenia and anaemia. We did not observe any partial or complete tumour response. At 3 months, two patients had stable disease and at 6 months, all patients had progressed. The median overall survival was 5.27 months, median time to progression was 3 months. Conclusion, Rapamycin is well tolerated in patients with advanced HCC, but only minimally effective. [source] Psoralen and ultraviolet A and narrow-band ultraviolet B in inducing stability in vitiligo, assessed by vitiligo disease activity score: an open prospective comparative studyJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 10 2007A Bhatnagar Abstract Background Vitiligo is a common pigmentary disorder with great cosmetic and psychological morbidity and an unpredictable course. No treatment available is a definitive cure. Systemic psoralen and ultraviolet A (PUVA) has been the mainstay of treatment. Narrow-band UVB (NBUVB) was later introduced. In this study, we have compared the phototherapy modalities PUVA and NBUVB in inducing stability in vitiligo, assessed by using vitiligo disease activity score (VIDA), for the first time. Aims To investigate the position of NBUVB vis-à-vis PUVA in terms of stability achieved during therapy as indicated by the VIDA scores. Subjects and methods It was an open, prospective study of 50 patients divided equally in PUVA and NBUVB groups. The study period was from January 2004 to June 2005. This study was done as a part of a larger project to compare the efficacy of mentioned modalities in degree of repigmentation. Results In the NBUVB group, disease activity was present in 40% patients before commencement of therapy, which was reduced to 16% at the end of therapy (statistically significant, P = 0.049). In the PUVA group, similar figures were 20% and 16%, respectively. In the NBUVB group, 50% of patients whose disease was active prior to commencement of therapy had less than 50% repigmentation, whereas an equal number of patients had repigmentation of more than 50%. Almost an equal number of stable patients had less than and more than 50% repigmentation. In the PUVA group, 4 of the 5 (80%) patients who had active disease had less than 50% repigmentation, whereas only 1 patient (20%) with active disease obtained more than 50% repigmentation. The time to attain stability was 3.6 ± 2.1 months in the NBUVB group and 3.22 ± 3.1 months in the PUVA group. Eight of the 10 (80%) patients with unstable disease in the NBUVB group achieved stability, whereas 2 of the 5 (40%) patients of similar pre-treatment status in the PUVA group achieved stability. Conclusion NBUVB was in a more statistically advantageous position vis-à-vis PUVA, in respect to stability achieved and efficacy in both active and stable disease in a comparable time period. [source] A Phase II Clinical Trial of Vinorelbine in Dogs with Cutaneous Mast Cell TumorsJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 2 2008I.A. Grant Background: Few effective drugs are available to treat dogs with locally aggressive or metastatic mast cell disease. Hypothesis: Vinorelbine, a semisynthetic derivative of vinblastine, is an effective drug for the treatment of canine mast cell tumors (MCT). Animals: Twenty-four dogs with cutaneous MCT. Methods: Dogs with at least 1 measurable, cytologically confirmed, and previously untreated cutaneous MCT received a single treatment with vinorelbine at the previously established dosage of 15 mg/m2 IV. Tumor measurements and CBC were evaluated before and 7 days after treatment. Adverse events were graded according to Veterinary Cooperative Oncology Group (VCOG) guidelines. Statistics: Data were accrued in accordance with a Simon's 2-stage design with a noninteresting response rate of .05, a target response of .25, and , and , values of .10. Results: Three of 24 dogs (13%) had a response to treatment, including 1 measurable complete response and 1 measurable partial response. The 3rd dog had microscopic complete response to treatment with stable measurable disease. Twenty other dogs (83%) had stable disease and 1 dog (4%) had progressive disease. Neutropenia occurred in 13 dogs (54%) (grade 1, n = 4; grade 3, n = 6; grade 4, n = 3). Gastrointestinal toxicity occurred in 11 dogs (46%) (anorexia: grade 1, n = 3; grade 2, n = 1; grade 3, n = 1; diarrhea: grade 1, n = 2; grade 3, n = 1; vomiting: grade 1, n = 5; grade 3, n = 1). Conclusions and Clinical Importance: Vinorelbine was associated with an overall response rate of 13% and a high prevalence of neutropenia. Additional studies are indicated to determine if repeated dosing of vinorelbine or combination of vinorelbine with other drugs increases the observed biologic activity against canine MCT. [source] Serum C-Reactive Protein Concentration as an Indicator of Remission Status in Dogs with Multicentric LymphomaJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 6 2007Lise Nielsen Background: The acute-phase protein C-reactive protein (CRP) is used as a diagnostic and prognostic marker in humans with various neoplasias, including non-Hodgkin's lymphoma. Objective: To evaluate if CRP could be used to detect different remission states in dogs with lymphoma. Animals: Twenty-two dogs with untreated multicentric lymphoma. Methods: Prospective observational study. Blood samples were collected at the time of diagnosis, before each chemotherapy session, and at follow-up visits, resulting in 287 serum samples. Results: Before therapy, a statistically significant majority of the dogs (P= .0019) had CRP concentrations above the reference range (68%, 15/22). After achieving complete remission 90% (18/20) of the dogs had CRP concentrations within the reference range, and the difference in values before and after treatment was statistically significant (P < .001). CRP concentrations of dogs in complete remission (median, 1.91; range, 0.2,103) were significantly different (P= .031) from those of dogs with partial remission (median, 2.48; range, 0,89), stable disease (median, 1.77; range, 1.03,42.65), or progressive disease (median, 8.7; range, 0,82.5). There was profound variation of CRP measurements within each dog. Conclusions: CRP is useful in determining complete remission status after treatment with cytotoxic drugs. However, the individual variation between dogs means CRP concentration is not sufficiently different in other remission states to permit its use in monitoring progression of the disease. Greater reliability in determining remission status might be achieved by combining CRP concentration with other serum markers. [source] Effects of L-Asparaginase on Plasma Amino Acid Profiles and Tumor Burden in Cats with LymphomaJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 4 2007A.K. LeBlanc Background: L-Asparaginase (Elspara), is an Escherichia coli -derived enzyme that depletes lymphoma cells of asparagine, inhibiting protein synthesis and resulting in cell death. The single agent response rate in cats with lymphoma and impact of L-asparaginase on plasma amino acid concentrations is unknown. Hypotheses: L-Asparaginase significantly reduces plasma asparagine concentrations and has demonstrable efficacy against untreated lymphoma in cats. Animals: Thirteen cats with confirmed lymphoma (LSA) of any anatomic site were given 1 dose 400 IU/kg IM) of L-asparaginase for initial LSA treatment. Methods: Plasma collected at 0, 2, and 7 days after L-asparaginase therapy was assayed for ammonia, asparagine, aspartic acid, glutamine, and glutamic acid concentrations. Cats were restaged 7 days later to assess tumor response. Results: Eight cats had T-cell LSA, 4 cats had B-cell LSA, and 1 cat's immunophenotype was unknown. Two complete and 2 partial responses to L-asparaginase were seen. Four cats had stable disease, and 5 cats had progressive disease. Ammonia and aspartic acid concentrations were increased from baseline at 2 and 7 days posttreatment. Asparagine concentrations were decreased from baseline at 2 days but not 7 days posttreatment. Glutamic acid concentrations were increased at day 2 compared to day 7 posttreatment but not compared to baseline. Glutamine concentrations were unchanged. Conclusions and Clinical Importance: L-Asparaginase significantly reduced asparagine concentrations within 2 days of treatment, but this effect was lost within 7 days. The apparent overall response rate of feline LSA to L-asparaginase in this study was 30%. [source] The natural history of chronic hepatitis BJOURNAL OF VIRAL HEPATITIS, Issue 2007C.-L. Lai Summary., The natural history of chronic hepatitis B is dependent on the age of acquiring the hepatitis B infection. Those who are infected at adolescence or adulthood (including most of the Caucasians) tend to have stable disease after hepatitis B e antigen seroconversion with normal serum alanine aminotransaminase (ALT) and hepatitis B virus (HBV) DNA levels <105 copies/mL (20 000 IU/mL). In contrast, those who are infected at birth or early childhood (including the majority of the world's hepatitis B carriers, i.e. Asians) have a prolonged immune tolerance phase followed by a prolonged immune clearance phase. A proportion of these patients have progressive disease after HBeAg seroconversion with HBV DNA <104 copies/mL (<2000 IU/mL) and ALT between 0.5 and 2× upper limit of normal. Core promoter mutations may play a part in the development of cirrhosis-related complications. However, continuing viral replication, even at a relatively low level of <104 copies/mL (<2000 IU/mL), is probably the most important factor for the development of complications. [source] An open-label, phase 2 trial of denosumab in the treatment of relapsed or plateau-phase multiple myeloma,,AMERICAN JOURNAL OF HEMATOLOGY, Issue 10 2009Ravi Vij RANKL is a key mediator of osteoclast differentiation, activation, and survival. Preclinical data suggest that aberrant production and activation of osteoclasts may influence proliferation of multiple myeloma (MM) cells in the bone marrow. Reports have also shown that inhibiting RANKL may have a direct effect on RANK-expressing myeloma cells and a therapeutic role in treating the disease. In mouse myeloma models, inhibition of RANKL led to reduced serum paraprotein levels and tumor burden. Based on this hypothesis, this proof-of-concept, single-arm study investigated whether RANKL inhibition with denosumab could reduce serum M-protein levels in relapsed or plateau-phase myeloma subjects. All subjects received denosumab monthly, with loading doses on days 8 and 15 of month one, until disease progression or subject discontinuation. Results of this ongoing study demonstrated that no subjects in either cohort met the protocol-defined objective response criteria of complete response (CR) or partial response (PR), but that denosumab effectively inhibited the RANKL pathway regardless of previous exposure to bisphosphonates, as evidenced by suppressed levels of the bone turnover marker, serum C-terminal telopeptide of type 1 collagen (sCTx). Eleven (21%) subjects who relapsed within 3 months before study entry maintained stable disease for up to 16.5 months. Nineteen (46%) subjects with plateau-phase myeloma maintained stable disease for up to 18.3 months. The adverse event (AE) profile for denosumab and its dosing schedule in these populations was consistent with that for advanced cancer patients receiving systemic therapy. Additional controlled clinical studies of denosumab in subjects with both relapsed and plateau-phase MM are warranted. Am. J. Hematol. 2009. © 2009 Wiley-Liss, Inc. [source] Phase I study of decitabine with doxorubicin and cyclophosphamide in children with neuroblastoma and other solid tumors: A children's oncology group study,,PEDIATRIC BLOOD & CANCER, Issue 4 2010MRCP, Rani E. George MD Abstract Background Demethylating agents may alter the expression of genes involved in chemotherapy resistance. We conducted a phase I trial to determine the toxicity and molecular effects of the demethylating agent, decitabine, followed by doxorubicin and cyclophosphamide in children with refractory solid tumors. Procedure Stratum A included children with any solid tumor; Stratum B included neuroblastoma patients only. Patients received a 1-hr decitabine infusion for 7 days, followed by doxorubicin (45,mg/m2) and cyclophosphamide (1,g/m2) on day 7. Pharmacokinetic studies were performed after the first dose of decitabine. Biological studies included methylation and gene expression analyses of caspase-8, MAGE-1 and fetal hemoglobin (HbF), and expression profiling of pre- and post-treatment peripheral blood and bone marrow cells. Results The maximum-tolerated dose of decitabine was 5,mg/m2/day for 7 days. Dose-limiting toxicities at 10,mg/m2/day were neutropenia and thrombocytopenia. Decitabine exhibited rapid clearance from plasma. Three of 9 patients in Stratum A and 4/12 patients in Stratum B had stable disease for ,4 months. Sustained MAGE-1 demethylation and increased HbF expression were observed in the majority of patients post-treatment (12/20 and 14/16, respectively). Caspase-8 promoter demethylation and gene expression were seen in 2/7 bone marrow samples. Differentially expressed genes were identified by microarray analysis. Conclusion Low-dose decitabine when combined with doxorubicin/cyclophosphamide has tolerable toxicity in children. However, doses of decitabine capable of producing clinically relevant biologic effects were not well tolerated with this combination. Alternative strategies of combining demethylating agents with non-cytotoxic, biologically targeted agents such as histone deactelyase inhibitors should be explored. Pediatr Blood Cancer. 2010;55:629,638. © 2010 Wiley-Liss, Inc. [source] Extended phase I evaluation of vincristine, irinotecan, temozolomide, and antibiotic in children with refractory solid tumors,PEDIATRIC BLOOD & CANCER, Issue 7 2010René Y. McNall-Knapp MD Abstract Background The combination of irinotecan, temozolomide, and vincristine is appealing because of potentially synergistic mechanisms of action and non-overlapping toxicities. This phase I study was designed to determine the toxicity and maximum tolerated dose (MTD) of escalating daily protracted doses of irinotecan given in this combination. With extended accrual, we more fully explored the toxicity of multiple courses at the MTD. Procedure Patients under 22 years with recurrent or refractory solid tumors were eligible. A course of chemotherapy was given every 28 days. Cefpodoxime was given for diarrhea prophylaxis. Vincristine (1.5,mg/m2, max 2,mg) was given intravenously (IV) on days 1 and 8. Temozolomide (100,mg/m2/day) was given orally on days 1,5. Irinotecan was given IV over 1,hr on days 1,5 and 8,12. Dose escalation was done in the standard 3,+,3 cohort design, starting at 15,mg/m2/day. Results Twenty-five of 26 eligible patients were evaluable for toxicity and response. They received 111 courses (1,13, median 4). Dose limiting toxicity (DLT,pancreatitis, transaminitis) was seen in two of three patients at dose level 2 (20,mg/m2). No patients at level 1 had DLT during the first two cycles. Thus, the MTD of irinotecan in this combination is 15,mg/m2/day,×,10 doses. Hematologic toxicity was mild and not prolonged. Grade 3 diarrhea was seen in five courses. Responses included two complete and two partial with 12 stable disease (SD) (median 6 months). Conclusions This combination is safe and shows activity in pediatric patients with recurrent malignancy. Pediatr Blood Cancer 2010;54:909,915 © 2010 Wiley-Liss, Inc. [source] Phase I study of paclitaxel with standard dose ifosfamide in children with refractory solid tumors: A Pediatric Oncology Group study (POG 9376)PEDIATRIC BLOOD & CANCER, Issue 3 2009James I. Geller MD Abstract Purpose A dose-escalation Phase I study of taxol (paclitaxel) administered in combination with standard dose ifosfamide was conducted in children with relapsed or refractory solid tumors. Primary objectives were to estimate the maximum tolerated dose (MTD) and to describe the dose-limiting toxicities (DLTs). Patients and Methods Paclitaxel was administered as a 6-hr continuous infusion (hr 0,6), followed by intravenous ifosfamide (2 g/m2/day,×,3 days) over 1 hr at hours 6,7, 24,25, and 48,49. Patients at dose level 1 received 250 mg/m2 paclitaxel. Subsequent dose escalation proceeded using a standard 3,×,3 Phase I design. Results Fifteen patients received a combined 46 courses of therapy. The median age was 14.5 years (range, 2,19 years), and diagnoses included sarcoma (7), neuroblastoma (3), and other (5). Three patients received paclitaxel at 250 mg/m2 (10 courses), six at 325 mg/m2 (19 courses), three at 425 mg/m2 (8 courses), and three at 550 mg/m2 (9 courses). DLTs occurred in 2/3 patients at 550 mg/m2 paclitaxel during cycle 1, including grade 3 hypotension and grade 4 anaphylaxis in 1 patient each. Common non-dose-limiting toxicities included bone marrow suppression and peripheral neuropathy. Response was evaluable in 14 patients and included mixed response (3), stable disease (5), and progressive disease (6). Conclusion Paclitaxel hypersensitivity reactions were dose limiting when the drug was administered as a 6-hr infusion. The MTD and recommended Phase II dose of paclitaxel administered as a 6-hr continuous intravenous infusion followed by standard dose intravenous ifosfamide is 425 mg/m2 paclitaxel. Pediatr Blood Cancer 2009;52:346,350. © 2008 Wiley-Liss, Inc. [source] A phase 2 trial of all- trans -retinoic acid in combination with interferon-,2a in children with recurrent neuroblastoma or Wilms tumor: A Pediatric Oncology Branch, NCI and Children's Oncology Group StudyPEDIATRIC BLOOD & CANCER, Issue 5 2007Peter C. Adamson MD Abstract Background The combination of the antiproliferative and differentiation-inducing effects of retinoids together with the antiproliferative, immunostimulatory, and differentiation-potentiating effects of interferon-, (IFN-,) were the basis for the development of this combination in pediatric patients with refractory neuroblastoma or Wilms tumor. Procedure A phase 2 trial of all- trans -retinoic acid (ATRA), administered orally at a dose of 90 mg/m2/day in three divided doses for 3 consecutive days per week, and IFN-,2a, administered subcutaneously daily at a dose of 3,×,106 U/m2/day for 5 consecutive days per week, in 4 week cycles was performed. A two-stage design was used for each disease stratum. Results Seventeen patients (16 evaluable) with neuroblastoma, median age 9 years, and 15 patients (14 evaluable) with Wilms tumor, median age 6 years, were enrolled. Overall, the combination was well tolerated, with headache being the most common toxicity observed. There were no complete or partial responses. The median number of cycles administered was 1 (range 1,9). Four patients with neuroblastoma had stable disease for 12 or more weeks. Conclusions The combination of ATRA and IFN-,2a was inactive in children with relapsed or refractory neuroblastoma and Wilms tumor. The lack of activity with this combination in children with refractory neuroblastoma is similar to the disappointing phase 2 results of single agent 13- cis -retinoic-acid (13cRA) and does not support further development of ATRA for children with relapsed neuroblastoma. Pediatr Blood Cancer 2007;49:661,665. © 2006 Wiley-Liss, Inc. [source] A phase I study of irinotecan administered on a weekly schedule in pediatric patientsPEDIATRIC BLOOD & CANCER, Issue 1 2006L. Bomgaars MD Abstract Background The objectives of this study were to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), pharmacokinetics, and anti-tumor effect of irinotecan in pediatric patients with recurrent or refractory malignancies. Procedure Twenty-three patients between 1 and 21 years of age, with a solid tumor refractory to standard therapy or for which there was no standard therapy were enrolled. Irinotecan was administered over 90 min weekly 4×, every 6 weeks. The initial dose level was 125 mg/m2/day, with subsequent escalations to 160 and 200 mg/m2/day. A MTD was defined in heavily-pretreated and less-heavily-pretreated (,2 prior chemotherapy regimens, no prior bone marrow transplantation, and no central axis radiation) patients. Pharmacokinetic studies were also performed. Results Neutropenia and diarrhea were the DLTs in heavily pretreated patients; the MTD was 125 mg/m2/day. Neutropenia was the DLT in less-heavily pretreated; the MTD was 160 mg/m2/day. Five patients had stable disease for two to four cycles including one patient each with rhabdomyosarcoma, Ewing sarcoma, neuroblastoma, and two patients with ependymoma. Irinotecan clearance was greater that that previously reported for children receiving high dose irinotecan. Conclusions The recommended phase II dose of irinotecan administered weekly 4×, every 6 weeks in children with solid tumors is 125 mg/m2/dose for heavily pretreated patients and 160 mg/m2/dose for less heavily pretreated patients. © 2005 Wiley-Liss, Inc. [source] Unusual evolution of an Epstein,Barr virus-associated leiomyosarcoma occurring after liver transplantationPEDIATRIC TRANSPLANTATION, Issue 5 2001Bénédicte Brichard Abstract: We report the case of a child who developed, 2 yr after orthotopic liver transplantation (OLTx) for biliary atresia, a multi-focal hepatic tumor with lymphonodular metastases, identified as an Epstein,Barr virus (EBV)-associated leiomyosarcoma. Chemotherapy was given without tumor response. Subsequently, slow growth of the tumor was observed. Immunosuppression was tapered and stopped 9 yr after transplantation. At the present time, 12 yr after the discovery of the first hepatic lesions, the patient is alive and completely symptom-free, the abdominal masses are stable, and liver function tests are completely normal. Smooth muscle tumors are increasingly recognized in children with various immunodeficiencies occurring after organ transplantation. This unusual evolution of a clinically aggressive tumor into a stable disease after restoration of immunity confirms that the immune status of the patient is a crucial factor. [source] | ||||||||||||||||||||||||||||||||||