Combination Chemotherapy with Etoposide, Ifosfamide, and Cisplatin (VIP) in Small Cell Lung Cancer

Park, Mi Young; Won, Joon Yeon; Park, Kyung Tae

Abstract

PURPOSE: A prospective phase II trial was conducted in patients with small cell lung cancer (SCLC) to determine whether the response rate, duration of response, and overall survival can be improved by a combination chemotherapy with etoposide, ifosfamide, and cisplatin (VIP).
MATERIALS AND METHODS
From May 1994 to April 1997, thirty-three previously untreated patients with SCLC received individualized treatment tailored to disease extent. Twenty-one patients with limited disease (LD) received six cycles of chemotherapy consisting of etoposide 120 mg/m2, ifosfamide 1,500 mg/m2, and cisplatin 25 mg/m2 all given intravenously on days 1, 3 and 5. Cycles were repeated every 3 weeks for six cycles. Thoracic radiotherapy was administered to 15 patients with LD of SCLC subsequently after initial two or three cycles of chemotherapy. Prophylactic cranial irradiation was given to complete responders of SCLC. Chemotherapy alone was administered to 12 patients with extensive disease (ED) of SCLC.
RESULTS
Complete response (CR) rate was 51% (LD 67%, ED 25%) and overall response rate was 94% (LD 95%, ED 92, p=0.022). And the median duration of response of all patients was 8 months (11 months in LD, 6.5 months in ED, p=0.042). With a median follow-up period of 13 months (3+~36), the median survival of all patients was 12 months (16 months in LD, 9.5 months in ED, p=0.006), and the median disease-free survival (DFS) of 17 CR patients was 12 months. Stage and performance status score were important prognostic factor, but sex, age, and LDH level did not affect the outcome significantly. Among 21 patients with LD, 15 patients received radiotherapy and 6 did not. The overall response rate of patients who received radiotherapy was significantly higher than that of patients who did not (p=0.045). But there were no significant differences in duration of response and OS between them (p=0.055, p=0.068, respectively). The major side effects (greater than grade 2 of WHO criteria) of evaluable 154 cycles of chemotherapy were alopecia (76%), nausea/vomiting (54%), leukopenia (27%), anemia (19%), and thrombocytopenia (15%).
CONCLUSION
VIP chemotherapy has produced a high complete remission rate and it is a safe and well-tolerated regimen in SCLC. However, compared to previous reports, it has not improved overall survival significantly. Further phase II and III studies are warranted to confirm the efficacy of VIP chemotherapy.