Gemcitabine plus irinotecan as first-line weekly therapy in locally advanced and/or metastatic pancreatic cancer.

Single-agent gemcitabine has been established as standard treatment for advanced pancreatic cancer since clinical studies have shown an improvement in overall survival and significant clinical benefit when compared to the best supportive care despite low overall objective response. Several phase II studies have tested other single agents and different gemcitabine-based regimens in pancreatic cancer, but both response and survival rates have remained low. Irinotecan, a topoisomerase I inhibitor currently approved for the treatment of metastatic colon cancer, has also demonstrated improved response rate in patients with pancreatic cancer. Our purpose was to determine the activity and toxicity of this regimen in patients with unresectable or metastatic pancreatic cancer. Patients with histologically confirmed pancreatic adenocarcinoma received gemcitabine 1000 mg/m2 plus irinotecan 100 mg/m2 IV on days 1, 8, and 15 of a 28-day cycle for 6-8 months. From February 2004 to April 2006, 33 patients were entered into this study, 32 of whom were evaluable for treatment response, toxicity, median time to progression, and median survival. Characteristics included a median age of 63 years (range 41-79), 21 males (64%), and 12 females (36%). One patient discontinued treatment due to adverse effects. The total number of cycles administered was 188 and the median number of cycles for patients was 5.6 (range 2-7). Thirty-two patients were assessable for toxicity and response. Grade 3 hematological toxicity occurred in 9% of patients and was primarily neutropenia. No grade >2 gastrointestinal toxicities or death due to treatment were observed. The most frequent nonhematological adverse event was fatigue. Ten patients responded to treatment with two complete responses (6.3%) and eight partial responses (25.0%), for an overall response rate of 31.3%; 11 patients achieved stable disease (34.3%). The median time to tumor progression and the median survival were 9.2 (95% CI: 6.0-12.4) and 11.8 (95% CI: 7.7-15.9) months, respectively, with a 2-year survival of 22%. On the basis of this trial, the combination of gemcitabine plus irinotecan, administered in a weekly schedule and at this dose, is well tolerated and offers encouraging activity in the treatment of advanced and/or metastatic pancreatic cancer.

Weekly administration of docetaxel and epirubicin as first-line treatment for hormone-refractory prostate carcinoma.

Androgen-independent prostate carcinoma (AICP) is one of the tumors that continue to respond poorly to chemotherapy. Recently, protocols based on the use of docetaxel have significantly improved survival for patients in this disease. In other types of neoplastic disease, combined therapy with taxanes and anthracycline derivatives has been shown to produce additive effects in terms of growth inhibition, and superior tolerability when associated with weekly administration schedules. These findings prompted us to examine the tolerability and efficacy of weekly treatment of AICP with docetaxel (DOX) plus epirubicin (EPI). We enrolled 35 chemotherapy-naive men with AICP (mean age 72 years, range 68-77) and normal hepatic, renal, and cardiac function. The chemotherapy protocol provided for the IV administration of DOX (30 mg/m2) and EPI (30 mg/m2) on days 1, 8, and 15 every 28 days. Treatment was continued for 6 months or until disease progression and/or unacceptable toxicity was observed. Serum levels of prostate-specific antigen (PSA) were monitored in all patients, and reductions from baseline values of >50% were considered indicative of positive responses to treatment. Thirty-four patients were included in the analysis of toxicity, and objective responses to treatment were assessed in the 28 patients with measurable lesions. Nineteen patients (56%) experienced PSA reductions of >50% that persisted for more than 4 weeks. The response to therapy was classified as complete in 1 of the 28 patients (4%) with measurable disease (at the lymph node level). Thirteen others (13/28, 46%) had partial responses, in nine (32%) the disease remained unchanged, and progression was observed in the remaining five (18%); overall response rate was 50% (CR + PR). Of the 27 patients with pain at the time of enrollment, 16 (59%) experienced pain reduction during treatment. The median time to disease progression was 11.7 months (95% CI: 7.7-15.7) while the median survival time was 18.7 months (95% CI: 12.3-25.1). During the study, four patients developed grade 3 anemia and leukopenia, which was reversible in all cases. Lower grades of asthenia, nausea, vomiting, diarrhea, and peripheral edema were also observed. There were no cases of cardiotoxic effects. Alopecia was frequent but reversible in all cases. The results of this preliminary study indicate that the combined administration of DOX and EPI for treatment of AIPC is effective and well tolerated. The weekly administration of the drug combination appears to be a promising approach to the treatment of these tumors.