Treatment of non-small cell lung cancer with gefitinib (???Iressa???, ZD1839): the Greek experience with a compassionate-use program

Abstract

This is a retrospective analysis of 150 patients with advanced non-small cell lung cancer who had failed prior treatment or were unfit for chemotherapy and were treated with oral gefitinib ('Iressa', ZD1839; AstraZeneca) 250 mg/day. Thirty-two patients who received gefitinib for 3 weeks or less were not included in the analysis. For the remaining 118 evaluable patients, the mean age was 63.1 years; most patients had received prior chemotherapy (97.5%), Eastern Cooperative Oncology Group performance status scores 0-2 (97.4%) and stage IV disease (64.4%). The majority were symptomatic (84.6%). Disease control was observed in 30 patients (25.4%), of whom five had a partial response and 25 had stable disease; 18 (15.3%) were not evaluable. Median duration of treatment was 29.9 weeks in responding patients and 11.5 in patients with progressive disease (p<0.0001). Median overall survival was 7.3 months (15.2 months for disease control) and median progression-free survival was 3.2 months. Gefitinib was well tolerated, with grade 3/4 skin rash and diarrhea seen in 2.5 and 4.2% of patients, respectively. Clinical benefit was evaluated using questionnaires before and following treatment with gefitinib. In 82 patients with completed questionnaires, evaluation revealed symptom improvement in 40.1% and improvement in general feeling in 31.4%. Epidermal growth factor receptor (EGFR) analysis found that efficacy did not correlate with tumor EGFR overexpression. Therefore, in this retrospective analysis, gefitinib treatment provided disease control in 25% of patients who derived significant palliative benefit.

Skin rash and bronchoalveolar histology correlates with clinical benefit in patients treated with gefitinib as a therapy for previously treated advanced or metastatic non-small cell lung cancer

“…Correlation between EGFR expression and a higher likelihood of response to EGFR TKI was postulated, but dismissed in small trials [37][38][39]. In the BR.21 trial lack of EGFR expression was associated with a decreased benefit from erlotinib when compared with patients treated with placebo.…”

Gefitinib: an adverse effects profile

“…Diarrhoea, mostly grade 1 -2, has been reported at an incidence of 12.8 -42% in compassionate use studies [36,38]. The incidence of grade 3 -4 diarrhoea in these studies ranged from 1 -4.2% [34,37]. Shah et al, advise their patients to take two 2 mg loperamide tablets at the onset of diarrhoea followed by one 2 mg tablet after every loose bowel movement up to a maximum of 10 tablets per day [46].…”

“…All adverse effects were grade 1 -2 except one patient who experienced a grade 3 rash. A review of adverse effects reported in compassionate use studies and the expanded access programme is presented in Table 3 [22,[25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40].…”

High epidermal growth factor receptor amplification rate but low mutation frequency in Middle East lung cancer population

“…Analysis of protein expression levels by immunohistochemistry (IHC) has so far yielded disappointing results. For example, in a retrospective analysis of 118 non-small cell lung cancer (NSCLC) patients who received gefitinib, Razis et al [2] found that efficacy did not correlate with tumor EGFR overexpression. Amann et al [3] demonstrated strong response to anti-EGFR treatment in an EGFR-amplified and EGFR-mutated NSCLC cell line but only an intermediate effect in another EGFR wild-type cell line with strong EGFR protein levels.…”