Phase I study of a novel capecitabine schedule based on the Norton-Simon mathematical model in patients with metastatic breast cancer Journal Article


Authors: Traina, T. A.; Theodoulou, M.; Feigin, K.; Patil, S.; Tan, L. K.; Edwards, C.; Dugan, U.; Norton, L.; Hudis, C.
Article Title: Phase I study of a novel capecitabine schedule based on the Norton-Simon mathematical model in patients with metastatic breast cancer
Abstract: Purpose: This study was conducted to determine, in patients with advanced-stage breast cancer, the maximum tolerated dose (MTD) of capecitabine administered orally for 7 days followed by a 7-day rest (7/7), a schedule based on a mathematical method for the optimization of anticancer drug scheduling. Patients and Methods: Eligible patients had measurable, metastatic breast cancer. There was no limit to number of prior treatments. A standard, three-patients-per-cohort dose-escalation scheme used flat-dose capecitabine beginning at 1,500 mg orally twice daily (bid) on a 7/7 schedule. Each cohort was monitored for 28 days before escalation to the next cohort to assess for delayed toxicity. Response was evaluated radiographically every 12 weeks; toxicity was assessed every 2 weeks. Results: Twenty-one patients were treated on study. The most frequently reported treatment-related grade 2/3 adverse events were hand-foot syndrome (29%), leukopenia/neutropenia (24%), and fatigue (19%). Grade 3 toxicity was transient and easily managed. Three patients experienced grade 3 hand-foot syndrome; one of these patients had grade 3 diarrhea. There were no grade 4 events. The MTD of capecitabine 7/7 is 2,000 mg twice daily. Conclusion: As predicted by mathematical modeling, capecitabine dosing for 7 days followed by a 7-day rest is well tolerated. Efficacy of this schedule is being determined in a phase II clinical trial in patients with advanced breast cancer. © 2008 by American Society of Clinical Oncology.
Keywords: cancer chemotherapy; clinical article; controlled study; clinical trial; disease course; drug tolerability; fatigue; neutropenia; bevacizumab; fluorouracil; diarrhea; drug dose comparison; drug dose reduction; drug efficacy; drug safety; drug withdrawal; nonhuman; recommended drug dose; side effect; unspecified side effect; liver neoplasms; capecitabine; lymph node metastasis; lymphatic metastasis; cancer grading; mouse; metastasis; computer assisted tomography; multiple cycle treatment; breast cancer; biological model; models, biological; anemia; antimetabolites, antineoplastic; leukopenia; nausea; stomatitis; thrombocytopenia; vomiting; lung neoplasms; drug administration schedule; antineoplastic activity; drug resistance; drug resistance, neoplasm; breast neoplasms; mathematical model; docetaxel; drug dose escalation; lymphocytopenia; thoracic neoplasms; lung tumor; dosage schedule comparison; evening dosage; morning dosage; chemically induced disorder; breast tumor; liver tumor; carcinoma; drug derivative; skin disease; drug monitoring; hyperbilirubinemia; maximum tolerated dose; phase 1 clinical trial; taxane derivative; drug administration; trastuzumab; drug dose increase; anthracycline; breast metastasis; hand foot syndrome; administration, oral; deoxycytidine; antineoplastic antimetabolite; thorax tumor; soft tissue neoplasms; soft tissue tumor; hematologic disease; skin ulcer; prodrug; oral drug administration; hematologic diseases; prodrugs; hand disease; foot dermatoses; hand dermatoses
Journal Title: Journal of Clinical Oncology
Volume: 26
Issue: 11
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2008-04-10
Start Page: 1797
End Page: 1802
Language: English
DOI: 10.1200/jco.2007.13.8388
PUBMED: 18398145
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 29" - "Export Date: 17 November 2011" - "CODEN: JCOND" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Kimberly Nicole Feigin
    20 Feigin
  2. Sujata Patil
    386 Patil
  3. Clifford Hudis
    848 Hudis
  4. Larry Norton
    580 Norton
  5. Lee K Tan
    131 Tan
  6. Tiffany A Traina
    154 Traina