Irinotecan and Carboplatin in Metastatic or Recurrent NSCLC: An Update
December 4th 2004The 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.
Cisplatin, Fluorouracil, Celecoxib, and RT in Resectable Esophageal Cancer: Preliminary Results
December 4th 2004Esophageal cancer frequently expresses cyclooxygenase-2 (COX-2)enzyme. In preclinical studies, COX-2 inhibition results in decreasedcell proliferation and potentiation of chemotherapy and radiation. Wereport preliminary results of a phase II study conducted by the HoosierOncology Group in patients with potentially resectable esophageal cancer.All patients received cisplatin at 75 mg/m2 given on days 1 and 29and fluorouracil (5-FU) at 1,000 mg/m2 on days 1 to 4 and 29 to 32with radiation (50.4 Gy beginning on day 1). Celecoxib (Celebrex) wasadministered at 200 mg orally twice daily beginning on day 1 untilsurgery and then at 400 mg orally twice daily until disease progressionor unexpected toxicities, or for a maximum of 5 years. Esophagectomywas performed 4 to 6 weeks after completion of chemoradiation. Theprimary study end point was pathologic complete response (pCR). Secondaryend points included response rate, toxicity, overall survival, andcorrelation between COX-2 expression and pCR. Thirty-one patientswere enrolled from March 2001 to July 2002. Respective grade 3/4 toxicitieswere experienced by 58%/19% of patients, and consisted of granulocytopenia(16%), nausea/vomiting (16%), esophagitis (10%), dehydration(10%), stomatitis (6%), and diarrhea (3%). Seven patients (24%)required initiation of enteral feedings. There have been seven deathsso far, resulting from postoperative complications (2), pulmonary embolism(1), pneumonia (1), and progressive disease (3). Of the 22 patients(71%) who underwent surgery, 5 had pCR (22%). We concludethat the addition of celecoxib to chemoradiation is well tolerated. ThepCR rate of 22% in this study is similar to that reported with the use ofpreoperative chemoradiation in other trials. Further follow-up is necessaryto assess the impact of maintenance therapy with celecoxib onoverall survival.