RESUMO
OBJECTIVE: To investigate the efficacy and toxicity of gemcitabine administration followed by the combination of fluorouracil (5-FU) modulated by folinic acid in patients with advanced, symptomatic pancreatic cancer. The main objective was to estimate tumour response and any improvement in patients' quality of life. PATIENTS: The study included 48 evaluable patients with metastatic disease with no prior chemotherapy. The study duration was 3 years. INTERVENTIONS: Gemcitabine 1000 mg/m(2) intravenously was given on days 1 and 8 followed by fluorouracil 350 mg/m(2) intravenously as a bolus biologically modulated by folinic acid 350 mg/m(2) intravenously given on days 1, 2, 8 and 9 in order to develop the conditions for any potential drug synergism. The regimen was administered every 3 weeks for 1 year or until disease progression. RESULTS: Objective partial responses were documented in ten (21%) patients (95% CI 10.5, 35). Twenty-two (46%) patients had stable disease while 16 (33%) patients had progressive disease. The median response duration was 8 months (range 4-20). The median time to progression was 6 months (range 2-24), while the median survival of the group was 7 months (range 3-36) and the probability of surviving beyond 12 months was 20%. Of the 44 patients with tumour-related symptoms who were considered evaluable for clinical-benefit response, 28 (70%) patients had pain improvement, 25 (52%) patients had improvement of their performance status, and nine (28%) patients experienced weight gain during treatment. Serum concentrations of cancer antigen (Ca-19-9) were decreased by more than 50% in 14 (37%) of the 38 assessable patients. Chemotherapy was well tolerated, with mild myelotoxicity. Gastrointestinal toxicity was moderate with mild mucositis. CONCLUSION: The regimen of gemcitabine and fluorouracil administered in this study was well tolerated and showed a moderate antitumour activity and a significant palliative effect on tumour-related symptoms. Because fluorouracil is a low toxicity combination agent for gemcitabine, other forms of the two-drug combination warrant further investigation.
RESUMO
This phase II trial studied the efficacy and toxicity of docetaxel-epirubicin, supported by granulocyte colony-stimulating factor, as first-line chemotherapy in metastatic breast cancer. Patients received epirubicin (60 mg/m2) followed 1 hour later by docetaxel (80 mg/m2) every 3 weeks for a maximum of 8 cycles or until disease progression. Prophylactic granulocyte colony-stimulating factor (5 micrograms/kg) was administered daily for 5 days. Sixty-nine patients were evaluable for efficacy and toxicity. Objective responses occurred in 45 patients (65%; 95% confidence interval: 53-76%), with 11 (16%) complete responses and 34 (49%) partial responses. Responses were observed at all metastatic sites. The median response duration was 8 months (range 4-68), median time to progression was 10 months (range 4-68) and median overall survival was 24 months (range 7-68): neutropenia was dose limiting (46% grade 3-4 toxicity). The left ventricular ejection, fraction measured in 50 patients, fell below normal in 14 patients (28%), 8 patients had grade 1 and 6 grade 2 cardiotoxicity, but none developed congestive cardiac failure. The docetaxel-epirubicin regimen is extremely effective in poor prognosis breast cancer patients with visceral metastases, with significant overall and complete responses, followed by prolonged survival in responders. Although myelosuppression remains the major toxicity, prophylactic GCSF administration was associated with a small percentage of neutropenic fever.