Search

Background: The current study was performed to evaluate the activity of combination chemotherapy with gemcitabine and irinotecan in patients with previously treated carcinoma of an unknown primary site., Methods: Patients with carcinoma of an unknown primary site who had received one previous chemotherapy regimen were eligible for this study. All patients received gemcitabine at a dose of 1000 mg/m2 intravenously (i.v.) and irinotecan at a dose of 100 mg/m2 i.v. on Days 1 and 8; treatment courses were repeated every 21 days. Patients were evaluated for response after completing two courses of treatment; responders/stable patients continued treatment for a recommended six courses., Results: Forty patients entered this multicenter, community-based Phase II trial between September 2000 and July 2003. Four of these 40 patients (10%) achieved objective responses (a partial response in 3 patients and a complete response in 1 patient). An additional 17 patients (43%) had stable disease/minor response at first reevaluation; 7 of these patients (18%) remained stable for longer than 6 months. The median survival for the entire group was 4.5 months, with 1-year and 2-year survival rates of 25% and 13%, respectively. The treatment was well tolerated by most patients. Neutropenia was the most common Grade 3/4 toxicity (according to the National Cancer Institute Common Toxicity Criteria, version 3.0) (occurring in 36% of patients). Myelosuppression-related complications were uncommon, as were severe nonhematologic toxicities., Conclusions: The combination of gemcitabine and irinotecan has modest activity and is well tolerated in patients with recurrent/refractory carcinoma of an unknown primary site. Treatment-related toxicity, particularly myelosuppression, appears to be less severe than toxicity produced by the taxane and platinum regimens frequently used in the first-line therapy of these patients. Evaluation of the gemcitabine and irinotecan combination as first-line therapy is indicated., ((c) 2005 American Cancer Society.)

A phase I study of carboplatin (Paraplatin) administered in two different dosing schedules (single dose every 4 weeks and weekly dosing) in combination with weekly irinotecan (CPT-11, Camptosar) was conducted in patients with relapsed or refractory advanced malignancies. Fifty-three patients with a variety of tumor types were randomly enrolled on the two different treatment regimens and have received a total of 163 cycles of treatment to date. Twenty-six patients received weekly irinotecan in combination with a single fixed dose of every-4-week carboplatin (arm 1). Initially, patients received irinotecan on days 1, 8, and 15, in combination with fixed-dose carboplatin at an area under the concentration-time curve (AUC) of 5.5 (Calvert formula) on day 1 every 28 days. Due to dose-limiting toxicities encountered at the first two dose levels, the protocol was amended to decrease the fixed dose of carboplatin to an AUC of 4.0 every 4 weeks. Dose-limiting toxicity was again encountered, so the day-15 dose of irinotecan was eliminated from the dosing regimen. The recommended phase II dose for heavily pretreated patients is irinotecan at 60 mg/m2 on days 1 and 8 in combination with carboplatin at AUC 4.0 on day 1 with cycles repeated every 28 days. Twenty-seven patients were treated with weekly irinotecan in combination with fixed-dose weekly carboplatin (arm 2). The initial dosing regimen consisted of irinotecan in combination with fixed-dose carboplatin at an AUC of 1.8 on days 1, 8, and 15, with treatment cycles repeated every 28 days. Due to the development of dose-limiting toxicities at the first two dose levels, the dosing regimen was subsequently amended to weekly irinotecan in combination with fixed-dose carboplatin at AUC 2.0 on days 1 and 8 only, and the dosing interval was shortened to every 21 days. With this amended regimen, the recommended phase II doses are irinotecan at 90 mg/m2 in combination with carboplatin at AUC 2.0 on days 1 and 8, with treatment cycles repeated every 21 days.