Biomedical subjects

Ulrich Gatzemeier

Publications and source records attributed to Ulrich Gatzemeier.

25 records · Page 2Linked to original sources

PubMed2003

Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma.

PURPOSE: Patients with malignant pleural mesothelioma, a rapidly progressing malignancy with a median survival time of 6 to 9 months, have previously responded poorly to chemotherapy. We conducted a phase III trial to determine whether treatment with pemetrexed and cisplatin results in survival time superior to that achieved with cisplatin alone. PATIENTS AND METHODS: Chemotherapy-naive patients who were not eligible for curative surgery were randomly assigned to receive pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 on day 1, or cisplatin 75 mg/m2 on day 1. Both regimens were given intravenously every 21 days. RESULTS: A total of 456 patients were assigned: 226 received pemetrexed and cisplatin, 222 received cisplatin alone, and eight never received therapy. Median survival time in the pemetrexed/cisplatin arm was 12.1 months versus 9.3 months in the control arm (P =.020, two-sided log-rank test). The hazard ratio for death of patients in the pemetrexed/cisplatin arm versus those in the control arm was 0.77. Median time to progression was significantly longer in the pemetrexed/cisplatin arm: 5.7 months versus 3.9 months (P =.001). Response rates were 41.3% in the pemetrexed/cisplatin arm versus 16.7% in the control arm (P <.0001). After 117 patients had enrolled, folic acid and vitamin B12 were added to reduce toxicity, resulting in a significant reduction in toxicities in the pemetrexed/cisplatin arm. CONCLUSION: Treatment with pemetrexed plus cisplatin and vitamin supplementation resulted in superior survival time, time to progression, and response rates compared with treatment with cisplatin alone in patients with malignant pleural mesothelioma. Addition of folic acid and vitamin B12 significantly reduced toxicity without adversely affecting survival time.

Adult↗

PubMed2003

A phase I study of ZD0473 combined with paclitaxel for the treatment of solid malignancies.

PURPOSE: ZD0473 is a cytotoxic platinum agent, which in preclinical studies has exhibited synergistic activity when combined with paclitaxel. The aim of this open-label phase I study was to determine the maximum tolerated dose (MTD), safety, and antitumour activity of ZD0473 followed by paclitaxel in patients with refractory solid malignancies. METHODS: Patients received paclitaxel and ZD0473 on day 1 every 3 weeks. Seven dose levels were planned (ZD0473 60-180 mg/m2, paclitaxel 135-175 mg/m2), with dose escalation dependent on the incidence of dose-limiting toxicity. RESULTS: Included in the study were 23 patients who received 76 treatment cycles at dose levels 1 (60 mg/m2 ZD0473, 135 mg/m2 paclitaxel) to 6 (150 mg/m2 ZD0473, 175 mg/m2 paclitaxel). Dose-limiting thrombocytopenia (platelet count <25x10(9)/l) occurred in two of six patients at dose level 6, which defined the MTD. Grade 3/4 haematological toxicities included: anaemia (21.7%), neutropenia (39.1%), thrombocytopenia (34.8%), and leucopenia (34.8%). The most common grade 3/4 non-haematological toxicities included: alopecia (13.0%), pleural effusion (13.0%), somnolence (8.7%), and vomiting (8.7%). Of the 23 patients, 11 (47.8%) had disease stabilization, including 4 with non-small-cell lung cancer (NSCLC) who had a > or =25% reduction in tumour dimensions. CONCLUSIONS: ZD0473 combined with paclitaxel has a manageable tolerability profile and shows some evidence of antitumour activity in patients with NSCLC.

Adult↗

PubMed2003

Phase II study of pemetrexed with and without folic acid and vitamin B12 as front-line therapy in malignant pleural mesothelioma.

PURPOSE: This phase II clinical study evaluated the efficacy of pemetrexed for the treatment of malignant pleural mesothelioma (MPM). PATIENTS AND METHODS: Patients with a histologically proven diagnosis of MPM, chemotherapy-naive measurable lesions, and adequate organ function received pemetrexed (500 mg/m2) intravenously over 10 minutes every 3 weeks. After a protocol change, most patients also received folic acid and vitamin B12 supplementation to improve safety. RESULTS: A total of 64 patients were enrolled. Nine (14.1%) of the 64 patients had a partial response. The Kaplan-Meier estimate for median overall survival was 10.7 months. Forty-three patients received vitamin supplementation for all courses of therapy, and 21 patients did not. Seven of the nine responders were vitamin supplemented. The median overall survival was 13.0 months for supplemented patients and 8.0 months for nonsupplemented patients. Vitamin-supplemented patients completed more cycles of therapy than nonsupplemented patients (median, six v two cycles, respectively). Grade 3/4 neutropenia (23.4%) and grade 3/4 leukopenia (18.8%) were the most common laboratory toxicities. Fatigue and febrile neutropenia were the most commonly reported nonlaboratory events (grade 3, 6.3%; grade 4, 0.0% each). The incidence of these toxicities was generally lower in the supplemented patients. CONCLUSION: Single-agent pemetrexed for MPM resulted in a moderate response rate (14.1%) and median overall survival of 10.7 months. Patients supplemented with folic acid and vitamin B12 tolerated treatment better (less toxicity and more cycles of treatment) and had a 5-month greater median overall survival than nonsupplemented patients. These results indicate that patients with MPM could benefit from single-agent pemetrexed treatment combined with vitamin supplementation.

Adult↗

PubMed2003

Long-term survival in SCLC after treatment with paclitaxel, carboplatin and etoposide--a phase II study.

PURPOSE: We evaluated the toxicity and feasibility of adding paclitaxel to a standard platinum/etoposide regimen in the first-line treatment of patients with small cell lung cancer (SCLC). PATIENTS AND METHODS: Eighty-nine patients with limited disease (LD) or extensive disease without distant metastases (ED I) were treated in this multi-centered phase II trial between April 1996 and June 1997. Paclitaxel administration (175 mg/m(2) by a 1 h intravenous infusion) was immediately followed by a 30 min infusion of carboplatin at an area under the concentration time curve (AUC) of 5 on day 1 and etoposide 50 mg orally twice daily (bid) was given on days 2-8. Courses were repeated every 21 days. Patients who had an objective response continued treatment for a maximum of 6 courses. RESULTS: Eighty-four patients were assessable for response. Overall response rate (RR) was 82.1% with 17.8% complete remissions and 64.3% partial remissions. Median survival for LD patients was 20.5 months with a 1 year survival rate of 71.4% and a 3 year survival rate of 21.4%. Median survival of ED I patients was 11 months with a 1 year survival rate of 31.3% and a 3 year survival rate of 3.1%. Overall median survival was 18.1 months with a 1 year survival rate of 56.8% and a 3 year survival rate of 14.8%. Median progression-free intervals were 12.3 months for patients with LD stage of the disease and 8 months with ED I stage. Grade 3/4 toxicity was primarily hematologic. Grade 3/4 leucopenia occurred in 16.0% of courses and febrile episodes were detected in 0.3% of courses. Non-hematologic toxicities were uncommon. Grade 3 GI-tract toxicities or peripheral neuropathy appeared in less than 1% of the courses. Toxicities were detected according to WHO toxicity criteria. CONCLUSION: Paclitaxel can be added at full dose (175 mg/m(2)) to a carboplatin/etoposide combination while maintaining a tolerable toxicity profile. Efficacy data, RR, progression-free interval and survival in both, extensive and limited stage patients compare favorably with other reported data. This new regimen will be further evaluated in comparison to standard regimens in a phase III trial.

Adult↗

PubMed2003

Targeting the HER1/EGFR receptor to improve outcomes in non-small-cell lung cancer.

Non-small-cell lung cancer represents a growing global burden and remains a therapeutic challenge. Only small improvements in survival have been made with standard chemotherapeutic approaches to advanced disease in recent history. Novel biologic targeted therapies offer the potential of improving patient management and treatment outcomes in non-small-cell lung cancer. Prominent among these novel agents are the HER1/epithelial growth factor receptor (EGFR) inhibitors. One of these agents, gefitinib (Iressa), is already approved for use in advanced, refractory non-small-cell lung cancer. Erlotinib (Tarceva) is a promising HER1/EGFR inhibitor in phase III evaluation as first-line therapy combined with chemotherapy and as second-/third-line monotherapy in advanced non-small-cell lung cancer. In addition, erlotinib is being evaluated in combination with the angiogenesis inhibitor bevacizumab (Avastin), a strategy combining two new modalities in cancer treatment. Results of these trials will provide important information on optimal use of these new targeted therapies and may offer the promise of improving the treatment of non-small-cell lung cancer.

Angiogenesis Inhibitors↗

PubMed2002

Phase I trials of pemetrexed.

The maximum tolerated dose of the multitargeted antifolate drug pemetrexed is 600 mg/m(2) every 3 weeks in heavily pretreated patients without folic acid supplementation. However, with folic acid supplementation, higher doses have been given without limiting side effects. The dose-limiting toxicities of pemetrexed are neutropenia, asthenia, and thrombocytopenia. Other adverse effects include anemia, anorexia, rash, nausea, vomiting, peripheral edema, diarrhea, mucositis, and reversible elevations of transaminase and creatinine levels. Multiple pemetrexed combination phase I trials have been completed or are underway. Without folic acid supplementation, pemetrexed doses of 400 to 600 mg/m(2)could be safely administered with full therapeutic doses of irinotecan, gemcitabine, cisplatin, carboplatin, oxaliplatin, and 5-fluorouracil. Preliminary data from other ongoing trials (with folic acid and vitamin B(12) supplementation) have similarly shown that pemetrexed doses of at least 400 to 500 mg/m(2) can be safely administered with therapeutic doses of vinorelbine, docetaxel, and paclitaxel. Combination studies of pemetrexed with agents active in breast cancer (doxorubicin, epirubicin, and cyclophosphamide) and chest radiotherapy are also now underway. Adverse effects of these combinations have included neutropenia, anemia, thrombocytopenia, asthenia, vomiting, diarrhea, rash, nausea, anorexia, mucositis, and reversible transaminase elevation. The phase I trials of pemetrexed have consistently shown activity against a broad range of tumor types, including colorectal cancer, pancreatic cancer, breast cancer, non-small cell lung cancer, and mesothelioma. This activity has been noted not only in the combination trials, but when pemetrexed is given as a single agent as well. Pemetrexed is a promising drug. It is active against a broad range of cancers, and it has manageable side effects that seem to be lessened with folic acid and vitamin B(12) supplementation.

Antimetabolites, Antineoplastic↗

PubMedDate not supplied

Hypoxic active drugs.

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Antineoplastic Combined Chemotherapy Protocols↗