Irinotecan and gemcitabine in patients with advanced non-small cell lung cancer, previously treated with cisplatin-based chemotherapy. A phase II study.
BACKGROUND
To evaluate the efficacy and tolerability of irinotecan plus gemcitabine administered every two weeks in patients with advanced non-small cell lung cancer (NSCLC) previously treated with cisplatin-based chemotherapy.


METHODS
Fifty patients with advanced NSCLC, refractory or resistant to cisplatin derivatives, were treated on an out-patient basis with irinotecan 150 mg/m2 intravenously (i.v.) and gemcitabine 1,800 mg/m2 i.v. on days 1 and 15, every two weeks. The response to treatment was evaluated every two cycles. The patients' median age was 59 years, 44 were men and 92% had a performance status (PS) of 0-1.


RESULTS
On an intent-to-treat analysis, 8 (16%) patients, [95% confidence interval (CI), 7.2% to 29.1%] achieved partial response (PR), 19 (38%) stable disease (SD) and 23 (46%) progressive disease (PD). The median time to tumor progression (TTP) was 5.5 months (range, 0.1 to 16.5 months), the median survival time was 8.1 months (range, 0.8 to 22.1 months) and the 1-year survival 36% (95% CI, 22.9% to 50.8%). Clinical benefit response, including improvement of PS, dyspnea, anorexia and fatigue, cessation of hemoptysis and fever and reduction of cough and pain, was observed in 10% to 44% of patients. No patient experienced grade 3/4 anemia. Grade 3/4 neutropenia and thrombocytopenia occurred in 7 (14%) and 8 (16%) patients, respectively. Five (10%) patients were hospitalized due to febrile neutropenia and were successfully treated with broad-spectrum antibiotics and G-CSF support. One (2%) patient experienced grade 4 fatigue and discontinued treatment. Other grade 3/4 adverse events included diarrhea (3 cases, 2 of whom required hospitalization), alopecia (5 cases), asthenia (2 cases) and allergy (2 cases). Eight (16%) patients required a dose reduction. There were no treatment-related deaths.


CONCLUSIONS
The combination of irinotecan and gemcitabine, administered every two weeks, demonstrated rather modest activity in advanced NSCLC patients who had previously been treated with cisplatin-based chemotherapy. It was well tolerated with mild toxicity and was associated with significant 1-year survival rate and symptomatic benefit response.
Pectasides
Dimitrios
D
2nd Department of Medical Oncology, Metaxas Memorial Cancer Hospital, 51 Botassi Street, 185 37 Piraeus, Greece. pectasid@otenet.gr
Mylonakis
Nikolaos
N
Farmakis
Dimitrios
D
Nikolaou
Maria
M
Koumpou
Maria
M
Katselis
Ioannis
I
Gaglia
Asimina
A
Kostopoulou
Vassiliki
V
Karabelis
Athanasios
A
Kosmas
Christos
C
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002945:Cisplatin / Q000494:pharmacology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D000093542:Gemcitabine
D003841:Deoxycytidine; D000077146:Irinotecan; D002945:Cisplatin; D002166:Camptothecin; D000093542:Gemcitabine