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Phase II Study of Docetaxel and Irinotecan in Metastatic or Recurrent Esophageal Cancer: A Preliminary Report

The outcomes for patients with metastatic or recurrent esophagealcancer are dismal, with 1-year survival rates of approximately 20%. Inthis phase II study, we studied the combination of docetaxel (Taxotere)and irinotecan (CPT-11, Camptosar) in patients with metastatic orrecurrent esophageal cancer. Eligible patients included those withhistologic or cytologic diagnosis of adenocarcinoma or squamouscancer of the esophagus or gastroesophageal junction who had receivedno previous chemotherapy for metastatic esophageal cancer. Previouschemotherapy in the neoadjuvant or adjuvant setting was allowed.Patients received irinotecan at 160 mg/m2 over 90 minutes followed bydocetaxel at 60 mg/m2 intravenously over 1 hour, with chemotherapycycles repeated every 21 days. Patients were reevaluated every twocycles. Of a planned 40 patients, 15 were enrolled, with 14 patientsevaluable for toxicity and 10 evaluable for response and survival. Thecombination of docetaxel and irinotecan resulted in a response rate of30%. An additional 40% achieved stable disease. The median survivalwas 130 days, with three patients still alive at the time of this analysis.The toxicities included 71% incidence of grade 4 hematologic toxicities,with 43% febrile neutropenia. One patient died of cecal perforationafter one cycle. There was no evidence of pharmacokinetic interaction,as systemic clearance of both drugs was similar to that seen after singleagentadministration. In conclusion, the regimen of docetaxel andirinotecan is active in metastatic or recurrent esophageal cancer.However, this combination chemotherapy regimen has an unacceptablerate of febrile neutropenia. This regimen needs to be modified toreduce the incidence of febrile neutropenia.

Latest Article

Gemcitabine and Irinotecan in Locally Advanced or Metastatic Biliary Cancer: Preliminary Report

Chemotherapy has had limited success in biliary tract cancer. Of thenewer agents, gemcitabine (Gemzar) and irinotecan (CPT-11, Camptosar)both have single-agent activity in patients with advanced disease.We conducted a phase II trial to study the efficacy and toxicity of thecombination of gemcitabine plus irinotecan in patients with locallyadvanced or metastatic biliary tract cancer. The study has enrolled 14patients with histologically or cytologically documented cancer of thebiliary tract or gallbladder with bidimensionally measurable disease,Eastern Cooperative Oncology Group performance status 0 or 1,decompressed biliary tree, and no prior exposure to chemotherapy.Gemcitabine at 1,000 mg/m2 and irinotecan at 100 mg/m2 were bothadministered on days 1 and 8, every 21 days. In patients who had lessthan grade 3 hematologic and less than grade 2 nonhematologic toxicityfollowing cycle 1, the dose of irinotecan was increased to 115 mg/m2 forsubsequent cycles. A total of 65 cycles of chemotherapy have beenadministered, with an average of 4.5 cycles per patient (range: 1 to 11cycles). The median treatment duration was 3 months (range: 0.75 to 8months). An objective partial response was determined radiographicallyin two patients (14%) while stable disease for periods ranging from 4to 11.5 months was noted in six patients (43%). Toxicity consisted ofgrade 3/4 neutropenia in seven patients (50%) with no episodes offebrile neutropenia, grade 3/4 thrombocytopenia in four (28%), grade3 diarrhea in two (14%), and grade 3 nausea in one patient. Thecombination of gemcitabine plus irinotecan appears to possess modestclinical activity, and it is well tolerated in patients with advanced biliarycancer. Patient accrual is ongoing to this study.