Biomedical subjects

Ulrich Kleeberg

Publications and source records attributed to Ulrich Kleeberg.

4 recordsLinked to original sources

PubMed2006

Reduced incidence of severe palmar-plantar erythrodysesthesia and mucositis in a prospective multicenter phase II trial with pegylated liposomal doxorubicin at 40 mg/m2 every 4 weeks in previously treated patients with metastatic breast cancer.

PURPOSE: The aim of this study was to assess whether the reduction in the total dose of pegylated liposomal doxorubicin (PLD) per cycle from 50 mg/m(2) every 4 weeks to 40 mg/m(2) every 4 weeks can effectively lower the incidence of treatment-related palmar-plantar erythrodysesthesia (PPE) and mucositis. METHODS: Patients received PLD 40 mg/m(2) every 4 weeks, and were evaluated for toxicity prior to each treatment and for response every 8 weeks. RESULTS: All patients were previously treated with at least one chemotherapy regimen for metastatic disease, and 72% of the patients had a prior exposure to an anthracycline. Forty-six evaluable patients received a median of four PLD cycles, with a median dose intensity of 10 mg/m(2)/week and a median cumulative dose of 160 mg/m(2). No National Cancer Institute Common Toxicity Criteria (NCI-CTC) grade 3 or 4 PPE was observed in these patients. NCI-CTC grade 3 or 4 mucositis occurred in 4.3% of patients, only. Response rates and survival results observed here were comparable to those observed with PLD 50 mg/m(2) every 4 weeks in a matched patient population. However, patients treated with PLD 40 mg/m(2) every 4 weeks experienced less PPE and mucositis and required clearly less dose reductions and treatment delays. CONCLUSION: The favorable safety profile observed in this study leads us to recommend the use of PLD 40 mg/m(2) every 4 weeks for patients with advanced breast cancer.

Adult↗

PubMed2005

Dacarbazine, cisplatin, and interferon-alfa-2b with or without interleukin-2 in metastatic melanoma: a randomized phase III trial (18951) of the European Organisation for Research and Treatment of Cancer Melanoma Group.

BACKGROUND: Based on phase II trial results, chemoimmunotherapy combinations have become the preferred treatment for patients with metastatic melanoma in many institutions. This study was performed to determine whether interleukin-2 (IL-2) as a component of chemoimmunotherapy influences survival of patients with metastatic melanoma. PATIENTS AND METHODS: Patients with advanced metastatic melanoma were randomly assigned to receive dacarbazine 250 mg/m2 and cisplatin 30 mg/m2 on days 1 to 3 combined with interferon-alfa-2b 10 x 10(6) U/m2 subcutaneously on days 1 through 5 without (arm A) or with (arm B) a high-dose intravenous decrescendo regimen of IL-2 on days 5 through 10 (18 x 10(6) U/m2/6 hours, 18 x 10(6) U/m2/12 hours, 18 x 10(6) U/m2/24 hours, and 4.5 x 10(6) U/m2 for 3 x 24 hours). Treatment cycles were repeated in the absence of disease progression every 28 days to a maximum of four cycles. RESULTS: Three hundred sixty-three patients with advanced metastatic melanoma were accrued. The median survival was 9 months in both arms, with a 2-year survival rate of 12.9% and 17.6% in arms A and B, respectively (P = .32; hazard ratio, 0.90; 95% CI, 0.72 to 1.11). There was also no statistically significant difference regarding progression-free survival (median, 3.0 v 3.9 months) and response rate (22.8% v 20.8%). CONCLUSION: Despite its activity in melanoma as a single agent or in combination with interferon-alfa-2b, the chosen schedule of IL-2 added to the chemoimmunotherapy combination had no clinically relevant activity.

Adult↗

PubMed2005

Prospective, double-blind, placebo-controlled, multicenter, randomized phase III study with orally administered budesonide for prevention of irinotecan (CPT-11)-induced diarrhea in patients with advanced colorectal cancer.

BACKGROUND: Unpredictable and severe diarrhea (NCI grade > or =3) remains a life-threatening adverse event in patients treated with irinotecan (CPT-11). The aim of this study was to evaluate the efficacy and safety of orally administered budesonide for prevention of CPT-11-induced delayed diarrhea in patients with advanced colorectal cancer. PATIENTS AND METHODS: A total of 56 patients with advanced colorectal cancer receiving CPT-11 therapy (125 mg/m2 once weekly) were enrolled in this multicenter trial. Patients were randomly treated with 3 mg budesonide orally 3 times daily versus placebo. Detailed assessment of diarrhea by monitoring stool frequency, stool consistency and loperamide rescue medication was made by keeping a diary. RESULTS: Diarrhea, defined as number of stools >4 occurring on a single day during the study period, could be prevented in 58.3% of the budesonide-treated patients compared to 38.5% of the patients under placebo. Patients in the budesonide group had less episodes (0.7 vs. 2.2 episodes) and a considerably shorter total duration of diarrhea (1.8 vs. 4.2 days) episodes than patients in the placebo group. Loperamide use was more frequent in the placebo than in the budesonide arm (55.6 vs. 41.7%). Also, exposure to rescue medication of loperamide was higher for placebo (36.2 capsules) than for budesonide (24.9 capsules). A superior prevention of diarrhea was observed for budesonide compared to placebo in the first cycle (14 vs. 10; p = 0.257), with more failures observed in the placebo group (16 vs. 10). CONCLUSION: This double-blind randomized trial failed to show that budesonide has a significant benefit in preventing CPT-11-induced diarrhea. While a trend exists, further trials are warranted.

Administration, Oral↗

PubMed2005

A multicentre phase II study on gefitinib in taxane- and anthracycline-pretreated metastatic breast cancer.

BACKGROUND: Epidermal growth factor receptor (EGFR) is considered to be a viable drug target in a variety of solid tumors. The clinical benefit and safety of the EGFR tyrosine kinase inhibitor gefitinib ('Iressa')1 was evaluated in this Phase II, multicentre study of patients with taxane and anthracycline pretreated, metastatic breast cancer. METHODS: Gefitinib (500 mg/day) was given to 58 patients until disease progression. Primary endpoint was the clinical response rate to the study treatment. RESULTS: One patient (1.7%) had objective partial tumor response of her liver and pleural metastasis. Fifty-seven patients (98.3%) were non-responders with 52 patients (89.7%) having progressive disease and five patients (8.6%) were not evaluable. Two patients reported a significant improvement in pain at metastatic sites (1 liver, 1 bone). The median time to progression was 61 days (95% CI : 54-82 days) and the proportion of patients alive and progression free at 6 months at trial closure was 1.8% (95% CI : 0.0-5.2%). The median survival time was 357 days (95% CI : 257-441 days). Fifty-four patients (93.1%) discontinued study medication prematurely due to disease progression and three (5.2%) due to adverse events (diarrhea, pruritus, peripheral edema). CONCLUSIONS: Gefitinib monotherapy at 500 mg daily did not appear to be efficacious in the treatment of heavily pretreated metastatic breast cancer patients. It was well tolerated and the side effect profile was as expected from current knowledge of the drug. There was no correlation between EGFR expression and response in this study.

Adult↗