Multicenter phase 2 study of patupilone for recurrent or progressive brain metastases from non-small cell lung cancer Journal Article

Authors: Nayak, L.; Deangelis, L. M.; Robins, H. I.; Govindan, R.; Gadgeel, S.; Kelly, K.; Rigas, J. R.; Peereboom, D. M.; Rosenfeld, S. S.; Muzikansky, A.; Zheng, M.; Urban, P.; Abrey, L. E.; Omuro, A.; Wen, P. Y.
Article Title: Multicenter phase 2 study of patupilone for recurrent or progressive brain metastases from non-small cell lung cancer
Abstract: BACKGROUND Treatment options for patients with non-small cell lung cancer (NSCLC) with brain metastases are limited. Patupilone (EPO906), a blood-brain barrier-penetrating, microtubule-targeting, cytotoxic agent, has shown clinical activity in phase 1/2 studies in patients with NSCLC. This study evaluates the efficacy, pharmacokinetics, and safety of patupilone in NSCLC brain metastases. METHODS Adult patients with NSCLC and confirmed progressive brain metastases received patupilone intravenously at 10 mg/m2 every 3 weeks. The primary endpoint of this multinomial 2-stage study combined early progression (EP; death or progression within 3 weeks) and progression-free survival at 9 weeks (PFS9w) to determine drug activity. RESULTS Fifty patients with a median age of 60 years (range, 33-74 years) were enrolled; the majority were men (58%), and most had received prior therapy for brain metastases (98%). The PFS9w rate was 36%, and the EP rate was 26%. Patupilone blood pharmacokinetic analyses showed mean areas under the concentration-time curve from time zero to 504 hours for cycles 1 and 3 of 1544 and 1978 ng h/mL, respectively, and a mean steady state distribution volume of 755 L/m2. Grade 3/4 adverse events (AEs), regardless of their relation with the study drug, included diarrhea (24%), pulmonary embolisms (8%), convulsions (4%), and peripheral neuropathy (4%). All patients discontinued the study drug: 31 (62%) for disease progression and 13 (26%) for AEs. Twenty-five of 32 deaths were due to brain metastases. The median time to progression and the overall survival were 3.2 and 8.8 months, respectively. CONCLUSIONS This is the first prospective study of chemotherapy for recurrent brain metastases from NSCLC. In this population, patupilone demonstrated activity in heavily treated patients. © 2015 American Cancer Society.
Keywords: adult; clinical article; aged; survival rate; overall survival; constipation; drug tolerability; salvage therapy; bevacizumab; erlotinib; area under the curve; cancer growth; diarrhea; drug efficacy; drug safety; drug withdrawal; unspecified side effect; liver dysfunction; conference paper; gemcitabine; cancer radiotherapy; chemotherapy; temozolomide; topotecan; prospective study; carboplatin; progression free survival; multiple cycle treatment; phase 2 clinical trial; steady state; nausea; vomiting; dehydration; peripheral neuropathy; cancer mortality; irinotecan; dyspnea; rash; lung embolism; drug fatality; hypokalemia; insomnia; drug accumulation; drug distribution; multicenter study; brain metastasis; muscle weakness; peripheral edema; drug clearance; open study; headache; maximum plasma concentration; drug half life; pemetrexed; non-small cell lung cancer; brain surgery; hematologic disease; epothilone b; brain metastases; drug elimination; non small cell lung cancer; patupilone; convulsion; human; male; female; priority journal; recurrent metastases; minimum plasma concentration
Journal Title: Cancer
Volume: 121
Issue: 23
ISSN: 0008-543X
Publisher: Wiley Blackwell  
Date Published: 2015-12-01
Start Page: 4165
End Page: 4172
Language: English
DOI: 10.1002/cncr.29636
PROVIDER: scopus
PUBMED: 26308485
Notes: Export Date: 15 January 2016 -- Conference Paper -- Source: Scopus
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MSK Authors
  1. Antonio Marcilio Padula Omuro
    176 Omuro
  2. Lauren E Abrey
    272 Abrey