ABSTRACT
BACKGROUND: No comparisons of different doses of docetaxel-capecitabine in patients with advanced gastric cancer have been performed. METHODS: Patients with previously untreated metastatic/locally advanced gastro-oesophageal or gastric adenocarcinoma were enrolled in a prospective multicentre phase II trial. Two sequential cohorts received docetaxel 75 mg m(-2) (day 1) plus capecitabine 1000 mg m(-2) twice daily (days 1-14) (cohort I) or docetaxel 60 mg m(-2) (day 1) plus capecitabine 800 mg m(-2) twice daily (days 1-14) (cohort II) every 3 weeks. The primary end point was confirmed overall response rate. RESULTS: In all, 91 patients were enrolled (cohort I, n=40; cohort II, n=51) and 87 were evaluable for efficacy (n=38, 49, respectively). Overall response rate was 50.0% in cohort I and 23.5% in cohort II (exploratory analysis, P=0.014). Median times to tumour progression and overall survival were 5.6 and 10.1 months in cohort I and 3.7 and 7.2 months in cohort II, respectively. Dose reductions for docetaxel and capecitabine were required in 50.0% and 57.5% of patients in cohort I and 11.8% and 15.7% in cohort II, respectively. CONCLUSION: Starting treatment with full doses and reducing promptly seems to be the more promisingly effective strategy than starting cautiously with lower doses. Docetaxel/capecitabine 75/2000 mg m(-2) is a manageable, convenient outpatient combination with promising efficacy against advanced gastric cancer.
Subject(s)
Adenocarcinoma/drug therapy , Adenocarcinoma/pathology , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Stomach Neoplasms/drug therapy , Stomach Neoplasms/pathology , Adult , Aged , Capecitabine , Cohort Studies , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Disease-Free Survival , Docetaxel , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Fluorouracil/administration & dosage , Fluorouracil/analogs & derivatives , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Staging , Prospective Studies , Taxoids/administration & dosage , Treatment OutcomeABSTRACT
The German Multicentre acute lymphoblastic leukaemia (ALL) study group (GMALL) performed a pilot study using pegylated asparaginase (PEG-ASP) in combination with high-dose methotrexate as consolidation therapy in the 05/93 protocol. The aim of the study was an intra-individual comparison of two different doses of PEG-ASP in 26 patients, with regard to the depletion of asparagine in serum and toxicity. 'Pharmacokinetic' monitoring was performed to evaluate the effect of an intra-individual dose escalation of PEG-ASP from 500 to 1000 U/m2 intravenously in successive doses. Serum asparaginase activity was targeted at > or =100 U/l for 1 week and > or =50 U/l for 10 d. The second course of PEG-ASP was administered to 23 patients. Due to hypersensitivity reactions in five patients, only 18 patients were evaluable for pharmacokinetic monitoring. With respect to the PEG-ASP activity, an effective depletion of asparagine could be postulated in the majority of patients during 10 d after the first administration. The effect of an intraindividual dose escalation form 500 to 1000 U/m2 was evaluable in 17 of 22 patients. An increment in peak PEG-ASP activity >70% was observed in 65% of the patients. PEG-ASP was well tolerated. Despite the long half-life of PEG-ASP, neither pancreatic nor central nervous toxicities occurred among the 26 adult patients treated in this pilot study.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Adolescent , Adult , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Asparaginase/administration & dosage , Asparaginase/adverse effects , Asparagine/blood , Blood Coagulation/drug effects , Drug Administration Schedule , Female , Humans , Liver/drug effects , Male , Methotrexate/administration & dosage , Methotrexate/adverse effects , Middle Aged , Pilot Projects , Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood , Precursor Cell Lymphoblastic Leukemia-Lymphoma/immunology , Remission InductionABSTRACT
BACKGROUND AND OBJECTIVE: Rituximab has shown a high activity in relapsed follicular lymphomas when given alone. Further on, phase-II-studies indicate that its addition to chemotherapy may improve the response rate substantially. However, so far, prospective randomized studies have not been available. PATIENTS AND METHODS: In 1998 the GLSG started a multicenter trial in patients with relapsed or refractory indolent lymphoma or mantle cell lymphoma. A fludarabine-containing regimen (FCM) was chosen for salvage therapy, with fludarabine 25 mg/m(2)/d 1-3, cyclophosphamide 200 mg/m(2) d 1-3 and mitoxantrone 8 mg/m(2) d 1. A total of four courses, every 4 weeks were given. Patients were prospectively randomized for FCM alone or the immunochemotherapy with R-FCM (375 mg/m(2) one day before FCM) RESULTS: About 147 randomized patients 93 had follicular, 40 mantle cell and 14 lymphoplasmocytic/-cytoid lymphoma. Statistical analysis was performed by sequential testing and indicated for 94 fully evaluable patients a significant advantage for the R-FCM-arm, with an overall response rate of 83 % as compared to 58%, when treated with FCM alone (CR: 35 % vs. 13 %). Similar improvements of remission rate were detected in the different lymphoma subgroups, especially in MCL (OR: 65 % vs. 33 %). Both treatment options were associated with hematological toxicities of grade III and IV, but well tolerated; infectious complications were rare, with no difference between the two treatment groups. CONCLUSION: This prospectively randomized trial demonstrates for the first time a significant improvement of the combined immunochemotherapy related to the remission rate in patients with relapsed or refractory indolent lymphoma.