Cancer Research and Treatment

Original Articles

Oral Etoposide, Ifosfamide and Cisplatin in the Treatment of Extensive Disease Small Cell Lung Cancer: Seok Jin Kim, Hwa Jung Sung, Kyong Hwa Park, So Young Yoon, Sang Cheul Oh, Jae Hong Seo, Chul Won Choi, Byung Soo Kim, Sang Won Shin, Yeul Hong Kim, Kwang Taek Kim, Young Ho Choi, Jun Suk Kim; Cancer Res Treat. 2002;34(6):421-425. Published online December 31, 2002; DOI: https://doi.org/10.4143/crt.2002.34.6.421

Abstract PDF: PURPOSE
The combination of cisplatin and etoposide has been a common first line regimen for the treatment of small cell lung cancer (SCLC). The schedule dependence, and equal efficacy, of the oral and intravenous dosing of etoposide has led to prolonged administration of oral etoposide, which is known to produce an encouraging response in SCLC. To improve the efficacy of the cisplatin/etoposide combination, we administered oral etoposide, with added ifosfamide, which had significant single agent activity against SCLC. We conducted this study to evaluate the efficacy and toxicity of the cisplatin, ifosfamide and oral etoposide (PIE) combination in patients with extensive small cell lung cancer.
MATERIALS AND METHODS
Twenty-five patients with histologically confirmed extensive small cell lung cancer were enrolled into this study between January 2000 and May 2002. They were treated with, cisplatin at 20 mg/ m2/day, ifosfamide 1.5 g/m2/day, with mesna (all given intravenously on Days 1~3), and oral etoposide 50 mg/m2 on days 4~17. This cycle was repeated every 4 weeks for up to 6 cycles. We evaluated the corresponding disease responses and toxicities.
RESULTS
The patients' characteristics were as follows: median age 65 years (32~75), 19 males and 6 females. The performance stati were ECOG 0 in 3 patients, ECOG 1 in 12 and ECOG 2 in 10. Sixteen patients had a partial response, 2 had a stable disease and 4 had a progressive disease. Thus, the overall objective response rate was 72.7% (95% CI: 49.6~88.4%), with a median response duration of 7 months (95% CI: 3.5~10.5 months). Myelosuppression was the major observed toxicity. Grades III and IV neutropenia were observed in 42 (46.1%) of the 91 cycles. Significant non-hematological toxicities (>or=Grade III) were uncommon, with the exception of nausea and vomiting.
CONCLUSION
The response rate to the combination of cisplatin, ifosfamide and oral etoposide was similar to that of other combination chemotherapy studies in patients with extensive disease small cell lung cancer. The toxicity of the regimen was considered acceptable.

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Concurrent Chemoradiation Therapy with Cisplatin and Oral Etoposide for Locally Advanced Non-small Cell Lung Cancer: Chang Won Paek, So Young Yoon, Jae Hong Seo, Chul Won Choi, Byung Soo Kim, Sang Won Shin, Yeul Hong Kim, Jae Jung Shim, Kyung Ho Kang, Jun Suk Kim, Chul Yong Kim, Myung Sun Choi, Young Ho Choi, Kwang Tak Kim; J Korean Cancer Assoc. 2000;32(4):682-689.

Abstract PDF: PURPOSE
Prognosis of locally advanced inoperable non-small cell lung cancer (NSCLC) treated with radiation therapy alone has been disappointing. In recent years, concurrent chemoradiation therapy has potential of improving both local and metastatic disease-free survival. This phase II study was undertaken to determine the feasibility, toxicity, response rate, local control rate, and survival duration of locally advanced NSCL patients treated with concurrent chemoradiation using cisplatin and oral etoposide. MATERIAL AND METHODS: Forty-seven patients were enrolled and forty-one patients were evaluable. Chemotheray consisted of cisplatin 50 mg/m2/IV on days 1 and 8 and oral etoposide 100 mg/day on days 1 to 5 and 8 to 12 which was repeated, every 4 weeks for two cycles during radiation therapy. Radiation therapy was administered to a total dose of 6300 cGY.
RESULTS
Among 41 evaluable patients, six patients achieved complete response, and twenty had partial response, for an overall response rate of 63.4% (95% confidence interval; 48.4% to 75.4%). Stable disease was reported in 10 patients (24.4%) and another 5 (12.2%) showed disease pro gression. Overall survival rate was 76% at 1 year, 34% at 2 years. Median survival duration was 17 months (range; 3 to 41 ). Eighty-three percents of patients had radiation pneumonitis but only one patients needed medical treatment.
CONCLUSION
Concurrent chemoradiation therapy with cisplatin and oral etoposide at this level is a well tolerated and feasible.

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Clinical Efficacy of Combination Chemotherapy with Cisplatin , Ifosfamide , and Oral Etoposide ( PIE ) in Advanced Non - Small Cell Lung Cancer: Yeul Hong Kim, Jae Hong Seo, Byung Soo Kim, Sang Won Shin, Jae Jung Shin, Kyung Ho Kang, Young Ho Choi, Kwang Tak Kim, Jun Suk Kim; J Korean Cancer Assoc. 1999;31(2):297-305.

Abstract PDF: 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.

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Prolonged Oral Etoposide in Combination with Intravenous Cisplatin for Advanced Non-small Cell Lung Cancer: Ki Hyun Kim, Sung Yong Oh, Hun Sik Jeong, Jong Tae Lee, Won Seng Kim, Ho Joong Kim, Sung Soo Yoon, Won Ki Kang, Hong Ghi Lee, Chong Heon Lee, Chan Hyung Park, Keun Chil Park; J Korean Cancer Assoc. 1999;31(1):105-111.

Abstract PDF: PURPOSE
Etoposide is a schedule-dependent agent and has a synergistic activity with cisplatin. We evaluated the response rate and the toxicity of prolonged oral etoposide in combination with intravenous cisplatin for the previously untreated patients with unresectable stage IIIB or IV non-small cell lung cancer (NSCLC).
MATERIALS AND METHODS
Between April 1996 and February 1998, 71 patients were enrolled. The median age was 61 years (range, 36~75) and male: female ratio was 54: 17. Fourteen patients had stage IIIB disease and 57 had stage IV. Sixty-two patients had ECOG performance status of 0 or 1, and 9 had 2. Forty-eight patients had adenocarcinoma, 19 had squamous cell carcinoma and 4 had poorly differentiated NSCLC. Treatment consists of daily oral etoposide 50 mg/m in 2 divided doses for 21 days and intravenous cisplatin 60 mg/m on day 1. The treatment was repeated every 28 days.
RESULTS
Sixty-four of 71 patients were evaluable. Complete response and partial response were observed in 1 and 21 patients, respectively. The overall response rate was 34.4% (95% confidence interval 23.9~46.6%) and the median response duration was 30 weeks (range 13-53 weeks). The median survival of 71 patients was 56 weeks (range 3. 96+ weeks). There was a significantly longer survival in responders (p=0.035). Toxicities were evaluated by WHO criteria. Hematologic toxicities of grade 3, 4 were as follows: anemia 12.3%, leukopenia 8.7%, neutropenia 19.2%, thrombocytopenia 1.8%. Non-hematologic toxicities of grade 3, 4 were as follows: nausea and vomiting 5.9%, stomatitis 14.7%, diarrhea 1.5%. Early treatment-related death occurred in 2 patients (2.8%) due to sepsis.
CONCLUSION
Combination chemotherapy with prolonged oral etoposide and intravenous cisplatin is easy to administer and has moderate activity with acceptable toxicities for NSCLC.

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