PMID- 17440682
OWN - NLM
STAT- MEDLINE
DCOM- 20070828
LR  - 20181201
IS  - 0167-6997 (Print)
IS  - 0167-6997 (Linking)
VI  - 25
IP  - 4
DP  - 2007 Aug
TI  - Erlotinib and vinorelbine in advanced malignant solid tumors: a phase I study.
PG  - 351-5
AB  - BACKGROUND: Erlotinib is an oral epidermal growth factor receptor tyrosine kinase 
      inhibitor (EGFR TKI). Vinorelbine, a vinca alkaloid, interferes with microtubule 
      assembly inhibiting mitosis during metaphase. Both drugs are commonly used as 
      single agents in the treatment of advanced non small cell lung cancer (NSCLC). 
      Given their efficacy in NSCLC and their non-overlapping toxicity profile, we 
      conducted a phase I study of erlotinib and vinorelbine to establish the 
      feasibility and safety of the combination and to determine the maximum tolerated 
      dose (MTD). PATIENTS AND METHODS: Patients with advanced solid tumors were 
      treated with vinorelbine intravenously on day 1 and 8 and erlotinib orally daily 
      on a 21 day schedule. The dose levels of vinorelbine/erlotinib were 25 
      mg/m(2)/100 mg, 25/150 and 30/150. RESULTS: Sixteen patients were enrolled. Five 
      patients were chemo-naive; 11 had one prior therapy. The majority of patients had 
      NSCLC (n = 7). Dose limiting toxicities included febrile neutropenia (4 patients) 
      and grade 5 infection (1 patient). Non-hematologic grade 3/4 toxicities included 
      diarrhea, hypokalemia, infection, dyspnea and mucositis. Of 12 patients 
      assessable for radiologic response, there were no objective responses; eight had 
      stable disease. CONCLUSIONS: (1) The MTD was vinorelbine 25 mg/m2 day 1 and 8 
      with erlotinib 100 mg/day every 21 days. (2) The combination was associated with 
      high rate of febrile neutropenia (25%). (3) Due to subsequent data demonstrating 
      a lack of efficacy of erlotinib in combination with platinum doublets in advanced 
      NSCLC, this combination has not been explored further.
FAU - Davies, Angela M
AU  - Davies AM
AD  - Davis Cancer Center, University of California, 4501 X Street, Suite 3016, 
      Sacramento, CA 95817, USA. angela.davies@ucdmc.ucdavis.edu
FAU - Ho, Cheryl
AU  - Ho C
FAU - Hesketh, Paul J
AU  - Hesketh PJ
FAU - Beckett, Laurel A
AU  - Beckett LA
FAU - Lara, Primo N Jr
AU  - Lara PN Jr
FAU - Lau, Derick H M
AU  - Lau DH
FAU - Gandara, David R
AU  - Gandara DR
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070418
PL  - United States
TA  - Invest New Drugs
JT  - Investigational new drugs
JID - 8309330
RN  - 0 (Quinazolines)
RN  - 5V9KLZ54CY (Vinblastine)
RN  - DA87705X9K (Erlotinib Hydrochloride)
RN  - Q6C979R91Y (Vinorelbine)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy
MH  - Erlotinib Hydrochloride
MH  - Feasibility Studies
MH  - Female
MH  - Humans
MH  - Lung Neoplasms/*drug therapy
MH  - Male
MH  - Middle Aged
MH  - Neutropenia/chemically induced
MH  - Quinazolines/administration & dosage
MH  - Vinblastine/administration & dosage/analogs & derivatives
MH  - Vinorelbine
EDAT- 2007/04/19 09:00
MHDA- 2007/08/29 09:00
CRDT- 2007/04/19 09:00
PHST- 2006/12/20 00:00 [received]
PHST- 2007/03/07 00:00 [accepted]
PHST- 2007/04/19 09:00 [pubmed]
PHST- 2007/08/29 09:00 [medline]
PHST- 2007/04/19 09:00 [entrez]
AID - 10.1007/s10637-007-9045-8 [doi]
PST - ppublish
SO  - Invest New Drugs. 2007 Aug;25(4):351-5. doi: 10.1007/s10637-007-9045-8. Epub 2007 
      Apr 18.