Annals of Oncology 15:19-27, 2004
© 2004 European Society for Medical Oncology
Original Paper |
Randomized phase II trial of gemcitabine–cisplatin with or without trastuzumab in HER2-positive non-small-cell lung cancer
Received 29 May 2003; revised 4 September 2003; accepted 30 September 2003Background:
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/m2 (days 1 and 8) and cisplatin 75 mg/m2 (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.
1 Krankenhaus Grosshansdorf, Grosshansdorf, Germany; 2 Cross Cancer Institute, Edmonton, Canada; 3 The Netherlands Cancer Institute, Amsterdam, The Netherlands; 4 Princess Margaret Hospital, Toronto, Canada; 5 Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy; 6 Roche Products Ltd, Welwyn Garden City, UK; 7 McGill University, Montreal, Canada
Key words: cisplatin, gemcitabine, HER2, non-small-cell lung cancer, trastuzumab
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