Phase i trial of weekly cisplatin, irinotecan and paclitaxel in patients with advanced gastrointestinal cancer Journal Article
| Authors: | Tew, W. P.; Radovich, D.; O'reilly, E.; Schwartz, G.; Schrag, D.; Saltz, L. B.; Kelsen, D. P.; Kepler, S.; Ilson, D. H. |
| Article Title: | Phase i trial of weekly cisplatin, irinotecan and paclitaxel in patients with advanced gastrointestinal cancer |
| Abstract: | 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<sup>2</sup>). Paclitaxel was followed by fixed doses of cisplatin (30 mg/m<sup>2</sup>) and irinotecan (50 mg/m<sup>2</sup>). 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<sup>2</sup> 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<sup>2</sup>, cisplatin (30 mg/m<sup>2</sup>), and irinotecan (50 mg/m <sup>2</sup>) 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. © 2008 Springer Science+Business Media, LLC. |
| Keywords: | adult; clinical article; treatment response; aged; middle aged; clinical trial; drug tolerability; fatigue; neutropenia; cisplatin; advanced cancer; cancer combination chemotherapy; cancer growth; diarrhea; drug dose reduction; drug efficacy; drug potentiation; drug safety; drug withdrawal; liver cell carcinoma; recommended drug dose; paclitaxel; metastasis; computer assisted tomography; multiple cycle treatment; erythropoietin; anemia; nausea; thrombocytopenia; antineoplastic combined chemotherapy protocols; dehydration; camptothecin; dexamethasone; antineoplastic activity; dose-response relationship, drug; irinotecan; drug dose escalation; drug hypersensitivity; febrile neutropenia; syncope; gastrointestinal neoplasms; chemotherapy induced emesis; hyponatremia; drug mechanism; neoplasm metastasis; single drug dose; granisetron; pancreas adenocarcinoma; loperamide; maximum tolerated dose; phase 1 clinical trial; recombinant granulocyte colony stimulating factor; drug dose regimen; esophageal adenocarcinoma; stomach adenocarcinoma; granulocyte colony stimulating factor; abdominal cramp; recombinant erythropoietin; esophageal squamous cell carcinoma; atropine; diphenhydramine; stomach obstruction; gastrointestinal cancer; phase i; cimetidine; artificial heart pacemaker; sinus bradycardia |
| Journal Title: | Investigational New Drugs |
| Volume: | 27 |
| Issue: | 4 |
| ISSN: | 0167-6997 |
| Publisher: | Springer |
| Date Published: | 2009-08-01 |
| Start Page: | 366 |
| End Page: | 373 |
| Language: | English |
| DOI: | 10.1007/s10637-008-9194-4 |
| PUBMED: | 18956138 |
| PROVIDER: | scopus |
| PMCID: | PMC3219507 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 30 November 2010" - "CODEN: INNDD" - "Source: Scopus" |
