Intercalated chemotherapy and erlotinib for non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutations.
Among attempts to delay development of resistance to tyrosine kinase inhibitors (TKIs) in patients with advanced non-small cell lung cancer (NSCLC) with activating mutations of epidermal growth factor receptor (EGFR), intercalated therapy has not been properly evaluated. In a phase II trial, 38 patients with EGFR mutated NSCLC in advanced stage were treated with 4 to 6 3-weekly cycles of intercalated schedule with gemcitabine (1250 mg/m2, days 1 and 4), cisplatin (75 mg/m2, day 2) and erlotinib (150 mg, days 5 - 15), followed by continuous erlotinib as maintenance. In addition to standard radiologic evaluation according to RECIST, PET/CT was done prior to treatment and at 6 months, using PERCIST as a method for assessment of response. The primary endpoint was progression-free survival (PFS). In general, tolerance to treatment was good, even among 8 patients with performance status 2-3 and 13 patients with brain metastases; grade 4 toxicity included 2 cases of neutropenia and 4 thrombo-embolic events. Complete response (CR) or partial response (PR) were seen in 15 (39.5%) and 17 (44.7%) cases, respectively. All cases of CR were confirmed also by PET/CT. Median PFS was 23.4 months and median overall survival (OS) was 38.3  months. After a median follow-up of 35 months, 8 patients are still in CR and on maintenance erlotinib. In conclusion, intercalated treatment for treatment-naive patients with EGFR activating mutations leads to excellent response rate and prolonged PFS and survival. Comparison of the intercalated schedule to monotherapy with TKIs in a randomized trial is warranted.
a Institute of Oncology , Ljubljana , Slovenia.|b Faculty of Medicine , University of Maribor , Slovenia.
Matjaz
M
Zwitter
a Institute of Oncology , Ljubljana , Slovenia.
Mirjana
M
Rajer
a Institute of Oncology , Ljubljana , Slovenia.
Karmen
K
Stanic
a Institute of Oncology , Ljubljana , Slovenia.
Martina
M
Vrankar
a Institute of Oncology , Ljubljana , Slovenia.
Andrej
A
Doma
c Institute for Nuclear Medicine, University Clinical Center Ljubljana , Slovenia.
Anka
A
Cuderman
c Institute for Nuclear Medicine, University Clinical Center Ljubljana , Slovenia.
Marko
M
Grmek
d University Hospital for Pulmonary Diseases Golnik , Slovenia.
Izidor
I
Kern
a Institute of Oncology , Ljubljana , Slovenia.
Viljem
V
Kovac
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D066246:ErbB Receptors / Q000378:metabolism*; D000069347:Erlotinib Hydrochloride / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000093542:Gemcitabine
D003841:Deoxycytidine; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D002945:Cisplatin; D000093542:Gemcitabine
18F-FDG PET/CT; Cisplatin; EGFR activating mutations; NSCLC; TKI; erlotinib; gemcitabine; intercalated treatment; response evaluation