Benefit in lung function improvement and side-effect profile of long-term responders: an analysis of 14 NSCLC patients treated for at least 9 months with gefitinib.
BACKGROUND
Gefitinib is the first approved EGFR tyrosine-kinase inhibitor indicated for the treatment of patients with locally advanced (IIIB) or metastatic NSCLC after failure of platinum-based first-line therapy and docetaxel chemotherapy. Following rapid approval in Japan and accelerated approval based on phase-II results in the US, a large compassionate-use program has been set up in parallel to extended phase-III testing. Offering therefore access to state-of-the-art therapy to patients who are not candidates for clinical studies; Iressatrade mark EAP allows physicians to test the new EGFR inhibitor across a heterogeneous patient population characteristic for advanced NSCLC.


METHODS
After having treated 240 patients at the Grosshansdorf hospital, we have retrospectively analysed the efficacy and tolerability of 250 mg/day gefitinib in patients showing a long-term tumor control. We reviewed the patient records of 14 patients with advanced NSCLC that received daily gefitinib for at least 9 months.


RESULTS
Long-term tumor control, defined as confirmed objective tumor response for at least 6 months or disease stabilisation for above 9 months, was observed in chemo-naive patients as well as in fourth-line therapy patients for the latter ones independently of the composition of prior chemotherapy. Most patients (9/14) with such a lasting benefit were female; patients' histology was in most cases uniform: adenocarcinomas were dominant in women and bronchioloalveolar carcinoma in men. Patients with moderate to severe dyspnoea benefited from a measurable improvement of their respiratory capacity. No cumulative toxicity was observed; characteristic side-effects for gefitinib as grades 1-2 diarrhoea or mild to moderate skin toxicity were well manageable.


CONCLUSIONS
For 14 (6%) out of 240 patients with patterns of diffuse disseminated metastatic disease, gefitinib offered a lasting tumor control with a disease progression-free survival interval between 9 and 25 months. In parallel to therapy, patients' performance status (PS) could be conserved or even improved in many cases. Patients with lung function impairment, as well as patients with other disease-related symptoms obtained additional therapy benefits.
Onkologischer Schwerpunkt, Krankenhaus Grosshansdorf, Zentrum für Thoraxchirurgie, Studienkoordination, Wöhrendamm 80, D-22927 Grosshansdorf, Germany.
Martin
M
Reck
Ulrich
U
Gatzemeier
D000230:Adenocarcinoma / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D004334:Drug Administration Schedule; D004417:Dyspnea / Q000188:drug therapy / Q000209:etiology; D005260:Female; D005500:Follow-Up Studies; D000077156:Gefitinib; D006304:Health Status; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000502:physiology; D008175:Lung Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D012129:Respiratory Function Tests; D012189:Retrospective Studies; D012737:Sex Factors; D016019:Survival Analysis; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D011799:Quinazolines; D000077156:Gefitinib