Ifosfamide Enhances Efficacy of Cisplatin-Etoposide Chemotherapy

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In data presented at the 2nd European Lung Cancer Conference, a team of investigators said adding ifosfamide to a combination regimen of cisplatin plus etoposide demonstrated strong activity and tolerability in patients with small cell lung cancer (SCLC). Cisplatin plus etoposide, said the authors, is the worldwide standard for patients with SCLC, associated with a median survival of ~7 months in patients with extended disease.

The Italian researchers conducted a retrospective analysis of 59 consecutive patients (median age, 59 years) treated at one institution from December 1998 to 2008. The patients received the three-drug combination (PEI) as first- (n = 48), second- (n = 24), or third-line (n = 16) therapy. In 4 instances, it was administered subsequent to third-line therapy. The regimen consisted of 20 mg/m2 of cisplatin, 75 mg/m2 of etoposide, and 1200 mg/m2 of ifosfamide administered on days 1 to 4 of a 3-week cycle. On average, each patient received 2 lines of therapy and 6 cycles of PEI.

In the first-line subset, 75% of patients demonstrated partial response (PR) and 13% had complete response (CR), for an overall response rate (ORR) of 87% (Table). In the second line, PR was lower, at 42%, but CR increased to 17%; ORR was 58%. Only 13% of patients receiving third-line PEI had a PR and 13% had CR, for an ORR of 25%. In the 21 patients with limited disease, time-to- progression (TTP) in the first line was 12.7 months compared with 7.9 months in the second line and 5.8 months in the third line. Overall survival (OS) for these patients was 26.3 months. Not surprisingly, TTP was much shorter for patients with extended disease, at 6.8 months in the first line, 5.0 months in the second line, and 3 months in the third line. OS for patients with extended disease was approximately half (13.2 mo) the duration of OS for patients with limited disease. Two-year survival was 62% for patients with limited disease compared with 24% for patients with extended disease.

The most frequent adverse event was hematologic toxicity. More than half the patients developed grade 3-4 neutropenia. Anemia was reported in 27% of patients and thrombocytopenia in 21% of patients in the first line. Three patients died due to toxicity, all of whom had a PS score of 1. Overall, the researchers described toxicity as manageable. The authors concluded that the PEI regimen “confirmed a high activity and efficacy, both in limited-disease and extended-disease patients.”