Clinical Efficacy of Combination Chemotherapy with Cisplatin , Ifosfamide , and Oral Etoposide ( PIE ) in Advanced Non - Small Cell Lung Cancer

Kim, Yeul Hong; Seo, Jae Hong; Kim, Byung Soo; Shin, Sang Won; Shin, Jae Jung; Kang, Kyung Ho; Choi, Young Ho; Kim, Kwang Tak; Kim, Jun Suk

Abstract

PURPOSE: A prolonged administration of etoposide increases its effectiveness on the suggestion that pralonged maintenance of low levels is an important factor in determining its activity. Many studies have been tried to define the efficacy of combination of oral etoposide with other chemotherapeutic drugs such as cisplatin, 5-FU, and ifosfamide in patients with advanced non-small cell lung cancer (NSCLC). In this study, we evaluated the effectiveness and toxicities of combination chemotherapy of oral etoposide with intravenous cisplatin and ifosfamide in advanced NSCLC patients.
MATERIALS AND METHODS
Thirty-three patients with inoperable NSCLC who had measurable diseases and had not been treated with chemotherapeutic drug, were enrolled in this study (from May 1995 to April 1998). Treatment consisted of intravenous cisplatin (20 mg/m(2)/day, Day 1-3) and ifosfamide (1,800 mg/m(2)/day, Days 1-3) with Mesna (1,100 mg/m(2)/day, Days 1-3), and oral etoposide (50 mg/m(2)/day, Days 4-17). This treatment was repeated every 4 weeks. Patients showing stable disease or a better response were continued on treatment with the range of one to nine cycles (medium: 3 cycles). All patients were evaluated for the response, survival, and toxicity of this combination chemotherapy.
RESULTS
Eleven patients showed either complete responses [CR, 3 (9%)] or partial responses [PR, 8 (24%)]. The median number of treatment cycles were 5 (range, 3-9) for responders and 2 (range, 1-7) for non-responders. The responders had median response duration of 10 months and the overall survival of 12 months. The overall survival of responders were longer than that of non-responders (median 19 vs 5 months, p 0.0232). The toxicities of this treatment were tolerable without treatment related death. Limiting toxicities were myelosuppression and oral mucbsities, Grade 3 or 4 leukopenia and oral mucosities were observed in 34% and 9%, respectively.
CONCLUSION
The combination of cisplatin, ifosfamide, and oral etoposide produced encouraging response rates and median survival duration in patients with response. Further study of this combination is warranted in comparison with standard cisplatin+etoposide regimen or intravenous etoposide, cisplatin and ifosfamide regimen.