William Read, MD

The 1-year survival for patients with metastatic non–small-cell lungcancer is only around 35%. We are evaluating the combination ofirinotecan (Camptosar) and carboplatin (Paraplatin) in patients withstage IIIB and IV non–small-cell lung cancer. The first five patientsreceived irinotecan, 250 mg/m2 over 90 minutes followed by carboplatinat an area under the concentration-time curve of 5 over 1 hour. Thedose of irinotecan was subsequently reduced to 200 mg/m2 in view offebrile neutropenia in one of five patients. Chemotherapy cycles arerepeated every 21 days. Patients are reevaluated every two cycles. Of aplanned 42 patients, 37 have been enrolled so far. Of the 37 enrolledpatients, 25 received at least two cycles, 20 received at least four cycles,and 12 received all six planned cycles. Grade 4 neutropenia (absoluteneutrophil count < 500) occurred in 10 patients and 19 treatment cycles.Two of these patients also had grade 4 diarrhea. Thirty-six cycles (30%)were delayed for neutropenia, six of which occurred among the firstfive patients who received irinotecan at 250 mg/m2. Best response totherapy included 7 partial responses (23%), 11 stable disease (37%),with 12 patients having progressive disease (40%). The regimen ofirinotecan and carboplatin administered once every 3 weeks is tolerableand convenient, with early evidence of activity. The main toxicityis hematologic. This study is ongoing and actively accruing patients.

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.