Phase I Trial Using Weekly Administration of Gemcitabine and Docetaxel in Patients with Advanced Pancreatic Carcinoma

Abstract

Background: In advanced pancreatic carcinoma, no effective chemotherapy has been found yet due to the lack of appropriate response. The frequent use of gemcitabine is based on the fact that there is a significant improvement in the quality of life, but neither an effect on remission nor a detectable increase in survival rates could be observed. Therefore, the hypothesis was that the combination of gemcitabine with other drugs can result in a better outcome of patients. The aim of this study was to determine the maximally tolerable dosage of gemcitabine and docetaxel using a weekly administration regimen. Patients and Methods: Twenty-five patients with advanced or metastatic pancreatic carcinoma received combination chemotherapy using gemcitabine and docetaxel in a weekly administration regimen, beginning with 800 mg/m² of gemcitabine and 25 mg/m² of docetaxel. Four patients were originally enrolled for each of the seven different dosages of both drugs. Side effects were assessed according to the WHO standard. Quality of life was evaluated according to the Core Quality of Life Questionnaire (QLQ-C30) of the European Organization for Research and Treatment of Cancer. Results: Using the two maximal dosages of gemcitabine and docetaxel (gemcitabine, 800 and 1,000 mg/m², and docetaxel, 45 and 40 mg/m²; respectively), only 3 and 2 patients were enrolled, respectively, because of toxic side effects ≧ grade III according to WHO grading. Maximal dosages with tolerable side effects were 1,000 mg/m² of gemcitabine and 35 mg/m² of docetaxel given in weekly intervals. Main side effects of this combination chemotherapy were gastrointestinal symptoms and hematologic toxicity. Conclusion: Combination therapy with gemcitabine and docetaxel in advanced or metastatic pancreatic carcinoma is a well-tolerated and acceptable alternative treatment option with regard to the severity of side effects and its positive impact on quality of life and tumor-associated pain. According to the study endpoint, dosages of 1,000 mg/m² of gemcitabine and 35 mg/m² of docetaxel are recommended as maximum-tolerated doses (given in weekly intervals) for a future phase II trial.