PMID- 14679114
OWN - NLM
STAT- MEDLINE
DCOM- 20040527
LR  - 20221207
IS  - 0923-7534 (Print)
IS  - 0923-7534 (Linking)
VI  - 15
IP  - 1
DP  - 2004 Jan
TI  - Randomized phase II trial of gemcitabine-cisplatin with or without trastuzumab in 
      HER2-positive non-small-cell lung cancer.
PG  - 19-27
AB  - BACKGROUND: Trastuzumab provides significant clinical benefits in HER2-positive 
      metastatic breast cancer patients when administered in combination with 
      chemotherapy. Chemotherapy has also been shown to be beneficial in some patients 
      with advanced non-small-cell lung cancer (NSCLC). The present randomized phase II 
      trial examined the effect of adding trastuzumab to a standard chemotherapeutic 
      combination (gemcitabine-cisplatin) in patients with HER2-positive NSCLC. 
      PATIENTS AND METHODS: Patients with untreated stage IIIB/IV HER2-positive NSCLC 
      received up to six 21-day cycles of gemcitabine 1250 mg/m(2) (days 1 and 8) and 
      cisplatin 75 mg/m(2) (day 1). Patients in the trastuzumab arm received 
      trastuzumab 4 mg/kg intravenously (i.v.) followed by 2 mg/kg/week i.v. until 
      progression. RESULTS: Of 619 patients screened, 103 were eligible. Fifty-one 
      patients were treated with trastuzumab plus gemcitabine-cisplatin and 50 with 
      gemcitabine-cisplatin alone. Efficacy was similar in the trastuzumab and control 
      arms: response rate 36% versus 41%; median time to progression 6.3 versus 7.2 
      months; and median progression-free survival (PFS) 6.1 versus 7 months. Response 
      rate (83%) and median PFS (8.5 months) appeared relatively good in the six 
      trastuzumab-treated patients with HER2 3+ or fluorescence in situ hybridization 
      (FISH)-positive NSCLC. Addition of trastuzumab to gemcitabine-cisplatin was well 
      tolerated, side-effects were as expected, and trastuzumab did not exacerbate the 
      known toxicity of gemcitabine and cisplatin. Symptomatic cardiotoxicity was 
      observed in one trastuzumab-treated patient. Serum trastuzumab concentrations in 
      the presence of gemcitabine-cisplatin were comparable to those of trastuzumab 
      alone. CONCLUSIONS: Trastuzumab plus gemcitabine-cisplatin is well tolerated. 
      Clinical benefit was not observed. Although HER2 3+/FISH-positive patients may 
      benefit from trastuzumab, the subgroup is too small to provide definitive 
      information. No significant effect of gemcitabine-cisplatin on trastuzumab 
      pharmacokinetics was observed.
FAU - Gatzemeier, U
AU  - Gatzemeier U
AD  - Krankenhaus Grosshansdorf, Grosshansdorf, Germany. u.gatzemeier@t-online.de
FAU - Groth, G
AU  - Groth G
FAU - Butts, C
AU  - Butts C
FAU - Van Zandwijk, N
AU  - Van Zandwijk N
FAU - Shepherd, F
AU  - Shepherd F
FAU - Ardizzoni, A
AU  - Ardizzoni A
FAU - Barton, C
AU  - Barton C
FAU - Ghahramani, P
AU  - Ghahramani P
FAU - Hirsh, V
AU  - Hirsh V
LA  - eng
PT  - Clinical Trial
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - England
TA  - Ann Oncol
JT  - Annals of oncology : official journal of the European Society for Medical 
      Oncology
JID - 9007735
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antimetabolites, Antineoplastic)
RN  - 0 (Antineoplastic Agents)
RN  - 0W860991D6 (Deoxycytidine)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - P188ANX8CK (Trastuzumab)
RN  - Q20Q21Q62J (Cisplatin)
RN  - 0 (Gemcitabine)
SB  - IM
CIN - Ann Oncol. 2004 Jan;15(1):3-4. PMID: 14679110
MH  - Adult
MH  - Aged
MH  - Antibodies, Monoclonal/administration & dosage/adverse effects
MH  - Antibodies, Monoclonal, Humanized
MH  - Antimetabolites, Antineoplastic/administration & dosage/adverse effects
MH  - Antineoplastic Agents/*administration & dosage/adverse effects
MH  - Antineoplastic Combined Chemotherapy Protocols/administration & dosage/adverse 
      effects/*therapeutic use
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy
MH  - Cisplatin/administration & dosage/adverse effects
MH  - Deoxycytidine/administration & dosage/adverse effects/*analogs & derivatives
MH  - Female
MH  - Humans
MH  - Lung Neoplasms/*drug therapy
MH  - Male
MH  - Middle Aged
MH  - Prognosis
MH  - Random Allocation
MH  - Receptor, ErbB-2/*drug effects
MH  - Trastuzumab
MH  - Gemcitabine
EDAT- 2003/12/18 05:00
MHDA- 2004/05/28 05:00
CRDT- 2003/12/18 05:00
PHST- 2003/12/18 05:00 [pubmed]
PHST- 2004/05/28 05:00 [medline]
PHST- 2003/12/18 05:00 [entrez]
AID - S0923-7534(19)61546-2 [pii]
AID - 10.1093/annonc/mdh031 [doi]
PST - ppublish
SO  - Ann Oncol. 2004 Jan;15(1):19-27. doi: 10.1093/annonc/mdh031.