Document Detail

A Phase I clinical trial of the combination of imatinib and paclitaxel in patients with advanced or metastatic solid tumors refractory to standard therapy.
MedLine Citation:
PMID:  23014737     Owner:  NLM     Status:  MEDLINE    
PURPOSE: Pre-clinical data suggest that combining imatinib with traditional cytotoxic chemotherapy may improve imatinib efficacy. We conducted a Phase I study of imatinib in combination with paclitaxel in patients with advanced or metastatic solid tumors.
METHODS: Patients were accrued to the study in a standard 3 + 3 design. Patients were restaged every two cycles, and those with stable disease (SD), or better, continued study treatment without interruption. Maximally tolerated doses (MTDs) and pharmacokinetic profiles of combination imatinib and paclitaxel were assessed.
RESULTS: Fifty-eight patients were enrolled, including 40 in the Phase I dose escalation portion. Alternating dose escalation of imatinib and paclitaxel on a 28-day cycle resulted in MTDs of 800 mg imatinib daily, on days 1-4, 8-11, 15-18, and 22-25, and 100 mg/m(2) paclitaxel weekly, on days 3, 10, and 17. Two expansion cohorts, comprising 10 breast cancer patients and 8 patients with soft-tissue sarcomas, were enrolled at the MTDs. The most common adverse events were flu-like symptoms (64 %) and nausea/vomiting (71 %). The most common Grade 3/4 toxicities were neutropenia (26 %), flu-like symptoms (12 %), and pain (12 %). There were no relevant differences in the pharmacokinetic profiles of either drug when given in combination compared with alone. Thirty-eight subjects were evaluable for response, 18 (47.4 %) of whom experienced clinical benefit. Five patients (13.2 %) had a partial response (PR) and 13 patients (34.2 %) had SD; the average time to progression in those with clinical benefit was 17 weeks (range: 7-28 weeks).
CONCLUSIONS: This combination of imatinib and paclitaxel was reasonably safe and tolerable, and demonstrated evidence of anti-tumor activity. Further exploration in disease-specific Phase II trials is warranted.
Michael J Pishvaian; Rebecca Slack; Eunice Y Koh; Jan H Beumer; Marion L Hartley; Ion Cotarla; John Deeken; Aiwu Ruth He; Jimmy Hwang; Shakun Malik; Kashif Firozvi; Minetta Liu; Beth Elston; Sandy Strychor; Merrill J Egorin; John L Marshall
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Publication Detail:
Type:  Clinical Trial, Phase I; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-09-27
Journal Detail:
Title:  Cancer chemotherapy and pharmacology     Volume:  70     ISSN:  1432-0843     ISO Abbreviation:  Cancer Chemother. Pharmacol.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-26     Completed Date:  2013-01-24     Revised Date:  2014-04-18    
Medline Journal Info:
Nlm Unique ID:  7806519     Medline TA:  Cancer Chemother Pharmacol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  843-53     Citation Subset:  IM    
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MeSH Terms
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols / administration & dosage*,  adverse effects*,  pharmacokinetics
Chemotherapy, Adjuvant
Cohort Studies
Disease Progression
Drug Administration Schedule
Drug Resistance, Neoplasm
Maximum Tolerated Dose
Middle Aged
Neoplasms / drug therapy*,  pathology*,  radiotherapy,  surgery
Neutropenia / chemically induced
Paclitaxel / administration & dosage,  adverse effects,  pharmacokinetics
Piperazines / administration & dosage,  adverse effects,  pharmacokinetics
Pyrimidines / administration & dosage,  adverse effects,  pharmacokinetics
Radiotherapy, Adjuvant
Severity of Illness Index
Treatment Outcome
Grant Support
P30 CA016672/CA/NCI NIH HHS; P30 CA051008/CA/NCI NIH HHS; P30-CA47904/CA/NCI NIH HHS
Reg. No./Substance:
0/Benzamides; 0/Piperazines; 0/Pyrimidines; 33069-62-4/Paclitaxel; BKJ8M8G5HI/imatinib

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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