OBJECTIVES: To determine the maximum tolerated dose (MTD), toxicities, and suitable dose for weekly 1-h paclitaxel combined with weekly cisplatin and irinotecan to treat advanced gastrointestinal malignancies. METHODS: Thirty patients with metastatic or locally advanced (unresectable or recurrent) gastrointestinal solid tumors were enrolled on this single-center, phase I study. Patients were treated with paclitaxel given over 1h at 1 of 4 dose levels (40, 50, 65, or 80 mg/m(2)). Paclitaxel was followed by fixed doses of cisplatin (30 mg/m(2)) and irinotecan (50 mg/m(2)). All treatment was administered sequentially, once a week, in 6-week cycles (4 weeks on, 2 weeks off). Dose-limiting toxicity (DLT) was defined as a 2-week delay in treatment for grade 3 or 4 non-hematologic toxicity, neutropenic fever, a 1-week delay for grade 4 hematologic toxicity, or a 2-week delay for grade 3 hematologic toxicity. RESULTS: Thirty patients were recruited; 28 patients were assessable for safety. Most of the patients (70%) had no prior chemotherapy. The primary first-cycle DLTs were neutropenia, diarrhea, and nausea. Paclitaxel at 65 mg/m(2) was defined as the MTD. The most common grade 3-4 toxicities observed during all cycles were neutropenia (57%), febrile neutropenia (11%), diarrhea (29%), fatigue (29%), and nausea (18%). No patients had G-CSF (Neupogen, Amgen Inc., Thousand Oaks, CA) support. Responses were observed in gastric, esophageal, and pancreatic cancers. CONCLUSION: Paclitaxel at 65 mg/m(2), cisplatin (30 mg/m(2)), and irinotecan (50 mg/m(2)) given weekly can be safely administered to patients with solid tumor malignancies. To improve cumulative toxicities, a schedule modification was required (3-week cycle; 2-on, 1-off) Neutropenia was the most common DLT. This combination showed substantial activity, particularly in patients with gastric and esophageal adenocarcinoma, and phase II evaluation could be considered.
OBJECTIVES: To determine the maximum tolerated dose (MTD), toxicities, and suitable dose for weekly 1-h paclitaxel combined with weekly cisplatin and irinotecan to treat advanced gastrointestinal malignancies. METHODS: Thirty patients with metastatic or locally advanced (unresectable or recurrent) gastrointestinal solid tumors were enrolled on this single-center, phase I study. Patients were treated with paclitaxel given over 1h at 1 of 4 dose levels (40, 50, 65, or 80 mg/m(2)). Paclitaxel was followed by fixed doses of cisplatin (30 mg/m(2)) and irinotecan (50 mg/m(2)). All treatment was administered sequentially, once a week, in 6-week cycles (4 weeks on, 2 weeks off). Dose-limiting toxicity (DLT) was defined as a 2-week delay in treatment for grade 3 or 4 non-hematologic toxicity, neutropenic fever, a 1-week delay for grade 4 hematologic toxicity, or a 2-week delay for grade 3 hematologic toxicity. RESULTS: Thirty patients were recruited; 28 patients were assessable for safety. Most of the patients (70%) had no prior chemotherapy. The primary first-cycle DLTs were neutropenia, diarrhea, and nausea. Paclitaxel at 65 mg/m(2) was defined as the MTD. The most common grade 3-4 toxicities observed during all cycles were neutropenia (57%), febrile neutropenia (11%), diarrhea (29%), fatigue (29%), and nausea (18%). No patients had G-CSF (Neupogen, Amgen Inc., Thousand Oaks, CA) support. Responses were observed in gastric, esophageal, and pancreatic cancers. CONCLUSION:Paclitaxel at 65 mg/m(2), cisplatin (30 mg/m(2)), and irinotecan (50 mg/m(2)) given weekly can be safely administered to patients with solid tumor malignancies. To improve cumulative toxicities, a schedule modification was required (3-week cycle; 2-on, 1-off) Neutropenia was the most common DLT. This combination showed substantial activity, particularly in patients with gastric and esophageal adenocarcinoma, and phase II evaluation could be considered.
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Authors: Nasser Hanna; Paul A Bunn; Corey Langer; Lawrence Einhorn; Troy Guthrie; Thaddeus Beck; Rafat Ansari; Peter Ellis; Michael Byrne; Mark Morrison; Subramanian Hariharan; Benjamin Wang; Alan Sandler Journal: J Clin Oncol Date: 2006-05-01 Impact factor: 44.544
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Authors: V M Herben; V R Panday; D J Richel; J H Schellens; N van der Vange; H Rosing; F D Beusenberg; S Hearn; E Doyle; J H Beijnen; W W ten Bokkel Huinink Journal: J Clin Oncol Date: 1999-03 Impact factor: 44.544
Authors: Eric Van Cutsem; Vladimir M Moiseyenko; Sergei Tjulandin; Alejandro Majlis; Manuel Constenla; Corrado Boni; Adriano Rodrigues; Miguel Fodor; Yee Chao; Edouard Voznyi; Marie-Laure Risse; Jaffer A Ajani Journal: J Clin Oncol Date: 2006-11-01 Impact factor: 44.544
Authors: L B Saltz; D Spriggs; L J Schaaf; G K Schwartz; D Ilson; N Kemeny; J Kanowitz; C Steger; M Eng; P Albanese; D Semple; C K Hanover; G L Elfring; L L Miller; D Kelsen Journal: J Clin Oncol Date: 1998-12 Impact factor: 44.544