Cancer Research and Treatment

Original Articles

Randomized Phase III Trial of Irinotecan Plus Cisplatin versus Etoposide Plus Cisplatin in Chemotherapy-Naïve Korean Patients with Extensive-Disease Small Cell Lung Cancer: Dong-Wan Kim, Hoon-Gu Kim, Joo-Hang Kim, Keunchil Park, Hoon-Kyo Kim, Joung Soon Jang, Bong-Seog Kim, Jin-Hyoung Kang, Kyung Hee Lee, Sang-We Kim, Hun Mo Ryoo, Jin-Soo Kim, Ki Hyeong Lee, Jung Hye Kwon, Jin-Hyuk Choi, Sang Won Shin, Seokyung Hahn, Dae Seog Heo; Cancer Res Treat. 2019;51(1):119-127. Published online March 12, 2018; DOI: https://doi.org/10.4143/crt.2018.019

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Purpose
This randomized phase III study was designed to compare the efficacy and safety of irinote-can plus cisplatin (IP) over etoposide plus cisplatin (EP) in Korean patients with extensive-disease small-cell lung cancer (SCLC).
Materials and Methods
Patients were randomly assigned to receive IP, composed of irinotecan 65 mg/m² intravenously on days 1 and 8+cisplatin 70 mg/m² intravenously on day 1 every 3 weeks, or EP, composed of etoposide 100 mg/m² intravenously on days 1, 2, 3+cisplatin 70 mg/m² intravenously on day 1, every 3 weeks for a maximum of six cycles, until disease progression, or until unacceptable toxicity occurred. The primary endpoint was overall survival.
Results
A total of 362 patients were randomized to IP (n=173) and EP (n=189) arms. There were no significant differences between IP and EP arms for the median overall survival (10.9 months vs. 10.3 months, p=0.120) and the median progression-free survival (6.5 months vs. 5.8 months, p=0.115). However, there was a significant difference in response rate (62.4% vs. 48.2%, p=0.006). The pre-planned subgroup analyses showed that IP was associated with longer overall survival in male (11.3 months vs. 10.1 months, p=0.036), < 65 years old (12.7 months vs. 11.3 months, p=0.024), and Eastern Cooperative Oncology Group performance status 0/1 (12.4 months vs. 10.9 months, p=0.040) patient groups. The severity of treatment-related adverse events such as grade 3/4 anemia, nausea and diarrhea was more frequent in patients treated with IP.
Conclusion
The IP chemotherapy did not significantly improve the survival compared with EP chemotherapy in Korean patients with extensive-disease SCLC.

Citations

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Effect of Trilaciclib Administered Before Chemotherapy in Patients With Extensive-Stage Small-Cell Lung Cancer: A Pooled Analysis of Four Randomized Studies
Ying Liu, Lin Wu, Dingzhi Huang, Qiming Wang, Chen Yang, Li Zhou, Shuguang Sun, Xiaomei Jiang, Ying Cheng
Cancer Treatment and Research Communications.2025; : 100869. CrossRef
Factors associated with posttraumatic stress and anxiety among the parents of babies admitted to neonatal care: a systematic review
Reem Malouf, Sian Harrison, Victoria Pilkington, Charles Opondo, Chris Gale, Alan Stein, Linda S. Franck, Fiona Alderdice
BMC Pregnancy and Childbirth.2024;[Epub] CrossRef
Real world results of locally advanced and metastatic lung cancer patients treated with platinum doublet chemotherapy in first line: Moroccan cohort
Hassan Abdelilah Tafenzi, Farah Choulli, Edwin Kelly Haag, Anass Baladi, Ismail Essaadi, Rhizlane Belbaraka
Translational Oncology.2024; 47: 102015. CrossRef
Clinical Benefits of new Systemic Therapy for Small‐Cell Lung Cancer Over Two Decades: A Cross‐Sectional Study
Yuejing Chen, Honghong Liu, Shaohua Bai, Xuejiao Han, Fei Jin, Bo Cui
The Clinical Respiratory Journal.2024;[Epub] CrossRef
Camptothecin and Its Derivatives from Traditional Chinese Medicine in Combination with Anticancer Therapy Regimens: A Systematic Review and Meta-Analysis
Paul O. Odeniran, Paradise Madlala, Nompumelelo P. Mkhwanazi, Mahmoud E. S. Soliman
Cancers.2024; 16(22): 3802. CrossRef
Efficacy and toxicity profile of first‐line treatment for extensive‐stage small cell lung cancer: A Bayesian network meta‐analysis
Guo Lin, Zhuoran Yao, Kai Kang, Hui Wang, Ren Luo, You Lu
Cancer Medicine.2023; 12(9): 10230. CrossRef
Therapeutic strategy analysis of patients with advanced stage high‐grade neuroendocrine cervical cancer: A real‐world multicenter study
Yuanyuan Zhang, Yi Huang, Suiyu Luo, Lin Li, Hongying Yang, Ziyi Wang, Yongmei Peng, Manni Huang, Jusheng An, Xi Yang, Jing Wang, Chunmei Li, Lingying Wu
International Journal of Gynecology & Obstetrics.2022; 158(3): 722. CrossRef
Systematic evaluation of the efficacy‐effectiveness gap of systemic treatments in extensive disease small cell lung cancer
Christine M. Cramer‐van der Welle, Franz M. N. H. Schramel, Bas J. M. Peters, John W. G. van Putten, Olaf H. Klungel, Harry J. M. Groen, Ewoudt M. W. van de Garde
Pharmacoepidemiology and Drug Safety.2021; 30(4): 445. CrossRef
Treatment Outcomes of 9,994 Patients With Extensive-Disease Small-Cell Lung Cancer From a Retrospective Nationwide Population-Based Cohort in the Korean HIRA Database
Jung Soo Lee, Seoree Kim, Soo-Yoon Sung, Yeo Hyung Kim, Hyun Woo Lee, Ji Hyung Hong, Yoon Ho Ko
Frontiers in Oncology.2021;[Epub] CrossRef
Comparative Efficacy and Safety of Immunotherapeutic Regimens with PD-1/PD-L1 Inhibitors for Previously Untreated Extensive-Stage Small Cell Lung Cancer: A Systematic Review and Network Meta-Analysis
Koichi Ando, Ryo Manabe, Yasunari Kishino, Sojiro Kusumoto, Toshimitsu Yamaoka, Akihiko Tanaka, Tohru Ohmori, Tsukasa Ohnishi, Hironori Sagara
Current Oncology.2021; 28(2): 1094. CrossRef
Efficacy of concurrent chemoradiotherapy for patients with limited-disease small-cell lung cancer: a retrospective, nationwide, population-based cohort study
Seo Ree Kim, Ji Hyung Hong, Soo-Yoon Sung, Yeo Hyung Kim, Sang Hoon Chun, Hyun Woo Lee, Jung Soo Lee, Yoon Ho Ko
BMC Cancer.2021;[Epub] CrossRef
Clinical significance of the cachexia index in patients with small cell lung cancer
Se-Il Go, Mi Jung Park, Gyeong-Won Lee
BMC Cancer.2021;[Epub] CrossRef
Sevens Cases of Neuroendocrine Carcinoma of the Nasal and Paranasal Sinuses
Ichiro Sekine, Kan Kishibe, Miki Takahara, Hiroaki Katada, Tatsuya Hayashi, Yasuaki Harabuchi
Nihon Bika Gakkai Kaishi (Japanese Journal of Rhinology).2021; 60(2): 169. CrossRef
Advances in Treatment of Recurrent Small Cell Lung Cancer (SCLC): Insights for Optimizing Patient Outcomes from an Expert Roundtable Discussion
Millie Das, Sukhmani K. Padda, Jared Weiss, Taofeek K. Owonikoko
Advances in Therapy.2021; 38(11): 5431. CrossRef
Impact of Value Frameworks on the Magnitude of Clinical Benefit: Evaluating a Decade of Randomized Trials for Systemic Therapy in Solid Malignancies
Ellen Cusano, Chelsea Wong, Eddy Taguedong, Marcus Vaska, Tasnima Abedin, Nancy Nixon, Safiya Karim, Patricia Tang, Daniel Y. C. Heng, Doreen Ezeife
Current Oncology.2021; 28(6): 4894. CrossRef
Geriatric Nutritional Risk Index as a prognostic marker in patients with extensive‐stage disease small cell lung cancer: Results from a randomized controlled trial
Gyeong‐Won Lee, Se‐Il Go, Dong‐Wan Kim, Hoon‐Gu Kim, Joo‐Hang Kim, Ho Jung An, Joung Soon Jang, Bong‐Seog Kim, Seokyung Hahn, Dae Seog Heo
Thoracic Cancer.2020; 11(1): 62. CrossRef
IRS2 Amplification as a Predictive Biomarker in Response to Ceritinib in Small Cell Lung Cancer
Mi-Sook Lee, Kyungsoo Jung, Ji-Young Song, Min-Jung Sung, Sung-Bin Ahn, Boram Lee, Doo-Yi Oh, Yoon-La Choi
Molecular Therapy - Oncolytics.2020; 16: 188. CrossRef
Etoposide and cisplatin versus irinotecan and cisplatin as the first‐line therapy for patients with advanced, poorly differentiated gastroenteropancreatic neuroendocrine carcinoma: A randomized phase 2 study
Panpan Zhang, Jie Li, Jian Li, Xiaotian Zhang, Jun Zhou, Xicheng Wang, Zhi Peng, Lin Shen, Ming Lu
Cancer.2020; 126(S9): 2086. CrossRef
Systematic review of first-line chemotherapy for chemo-naïve extensive-stage small-cell lung cancer: network meta-analysis
Hao Chen, Nobuyuki Horita, Kentaro Ito, Hideyuki Nagakura, Yu Hara, Nobuaki Kobayash, Masaki Yamamoto, Makoto Kudo, Takeshi Kaneko
Therapeutic Advances in Medical Oncology.2020;[Epub] CrossRef
A Retrospective Cohort Study on Pretreated Neutrophil-to-Lymphocyte Ratio and Prognosis of Small Cell Lung Cancer: Evidence of Effect Modification by Chemotherapy Regimen

Feiwen Liu, Shaozhang Zhou, Liping Tan, Huiqin Jiang, Yucong Huang
Cancer Management and Research.2020; Volume 12: 10341. CrossRef
Comparison of First-Line Treatments for Patients With Extensive-Stage Small Cell Lung Cancer
Ting Zhou, Zhonghan Zhang, Fan Luo, Yuanyuan Zhao, Xue Hou, Tingting Liu, Kai Wang, Hongyun Zhao, Yan Huang, Li Zhang
JAMA Network Open.2020; 3(10): e2015748. CrossRef
Thérapie ciblée et immunothérapie du cancer bronchique à petites cellules
J.-L. Pujol, C. Goze, C. Pujol, B. Roch
Revue des Maladies Respiratoires Actualités.2019; 11(3): 315. CrossRef
Irinotecan-platinum combination therapy for previously untreated extensive-stage small cell lung cancer patients: a meta-analysis
Fei Xu, Xiaoli Ren, Yuan Chen, Qianxia Li, Ruichao Li, Yu Chen, Shu Xia
BMC Cancer.2018;[Epub] CrossRef
Traitement médical du cancer bronchique à petites cellules : peut-on sortir de l’aire du cisplatine–étoposide ?
Jean-Louis Pujol, Benoît Roch, Camille N. Pujol, Catherine Goze
Bulletin du Cancer.2018;[Epub] CrossRef

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Randomized, Multi-center Phase II Trial of Docetaxel Plus Cisplatin Versus Etoposide Plus Cisplatin as the First-line Therapy for Patients with Advanced Non-Small Cell Lung Cancer: Nam-Su Lee, Hee-Sook Park, Jong-Ho Won, Dae-Sik Hong, Su-Taek Uh, Sang-Jae Lee, Joo-Hang Kim, Se-Kyu Kim, Myung-Ju Ahn, Jung-Hye Choi, Suk-Chul Yang, Jung-Ae Lee, Keun-Seok Lee, Chang-Yeol Yim, Yong-Chul Lee, Chul-Soo Kim, Moon-Hee Lee, Kab-Do Jung, Hanlim Moon, Yl-Sub Lee; Cancer Res Treat. 2005;37(6):332-338. Published online December 31, 2005; DOI: https://doi.org/10.4143/crt.2005.37.6.332

Abstract PDF PubReader ePub

Purpose

We prospectively conducted a multi-center, open-label, randomized phase II trial to compare the efficacy and safety of docetaxel plus cisplatin (DC) and etoposide plus cisplatin (EC) for treating advanced stage non-small cell lung cancer (NSCLC).

Materials and Methods

Seventy-eight previously untreated patients with locally advanced, recurrent or metastatic NSCLC were enrolled in this study. The patients received cisplatin 75 mg/m² on day 1 and either docetaxel 75 mg/m² on day 1 or etoposide 100 mg/m² on days 1 to 3 in the DC or EC arm, respectively, every 3 weeks.

Results

The objective response rate was 39.4% (15/38) and 18.4% (7/38) (p=0.023) in the DC and EC arms, respectively. The median time to progression (TTP) was 5.9 and 2.7 months (p=0.119), and the overall survival was 12.1 and 8.7 months (p=0.168) in the DC and EC arms, respectively. The prognostic factors for longer survival were an earlier disease stage (stage III, p=0.0095), the responders to DC (p=0.0174) and the adenocarcinoma histology (p=0.0454). The grades 3 and 4 toxicities were similar in both arms, with more febrile neutropenia (7.9% vs. 0%) and fatigue (7.9% vs. 0%) being noted in the DC arm.

Conclusion

DC offered a superior overall response rate than does EC, along with tolerable toxicity profiles, although the DC drug combination did not show significantly improved survival and TTP.

Citations

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Correlations between objective response rate and survival-based endpoints in first-line advanced non-small cell lung Cancer: A systematic review and meta-analysis
Sarah Goring, Nebibe Varol, Nathalie Waser, Evan Popoff, Greta Lozano-Ortega, Adam Lee, Yong Yuan, Laura Eccles, Phuong Tran, John R. Penrod
Lung Cancer.2022; 170: 122. CrossRef

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Review Article

Treatment of Small Cell Lung Cancer: Atsushi Horiike, Nagahiro Saijo; Cancer Res Treat. 2003;35(3):177-180. Published online June 30, 2003; DOI: https://doi.org/10.4143/crt.2003.35.3.177

Abstract PDF: Among patients with lung cancer, approximately 15% have small cell lung cancer (SCLC), SCLC is usually staged as either limited and extensive. Extensive-stage SCLC is treated primarily with chemotherapy. A recent Japanese randomized trial compared cisplatin and irinotecan (IP) with cisplatin and etoposide (EP). Patients in the IP arm did significantly better than patients in the EP arm. In the IP arm, the response rate was 84%, and the median overall survival period was 12.8 months. Limited- stage SCLC is usually treated with concurrent chemotherapy and accelerated radiation therapy, and approximately 20% of patients are cured. Future research should focus on optimizing chemotherapy regimens and radiation therapy schedules. The role of molecular targeted drugs in the treatment of SCLC must also be evaluated.

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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 Etoposide/Cisplatin Combination Chemotherapy (EP) and Thoracic Radiotherapy after Two Cycles of EP for Limited Stage Small Cell Lung Cancer: Hee Jung Sohn, Sang We Kim, Jin Hee Ahn, Hye Jin Kang, Sarah Park, Heon Nyoung Jung, Cheol Won Suh, Woo Kun Kim, Sang Wook Lee, Eun Kyung Choi, Sang Do Lee, Woo Sung Kim, Dong Sun Kim, Won Dong Kim, Jung Shin Lee; Cancer Res Treat. 2002;34(6):409-415. Published online December 31, 2002; DOI: https://doi.org/10.4143/crt.2002.34.6.409

Abstract PDF

Purpose
s: Although the standard management of limited stage small cell lung cancer is concurrent platinum-based chemotherapy with thoracic radiotherapy (TRT), the optimal timing of the TRT remains controversial. We investigated the feasibility of concurrent chemoradiation for the patients with limited stage small cell lung cancer after 2 cycles of combination chemotherapy with Etoposide/Cisplatin (EP).
MATERIALS AND METHODS
EP consisted of Etoposide 100 mg/m2 on day 1 to 3 and Cisplatin 70 mg/m2 on day 1. Six cycles were given to the responders every 4 weeks. Total 55 Gy (1.8 Gy once-daily or 1.2 Gy twice-daily, 5 days per week) of TRT were given to the patients who showed at least a partial response after 2 cycles of EP. The other patients were treated by the physician's decision. The patients with complete remission were recommended to receive prophylactic cranial irradiation.
RESULTS
Fifty patients were enrolled. Thirty-five (70%) of them showed responses (2 complete remissions and 33 partial remissions) after 2 cycles of EP. Thirty-three of the responders were given TRT starting with the 3rd cycle of EP. The nonresponders were treated with salvage chemotherapy and TRT. After completion of treatment for 50 patients, the overall response rate was 86% (29 complete remissions, 14 partial remissions). One patient (2%) showed stable disease, and 6 (12%) showed a progressive disease. The median progression free survival was 326 days and the median survival time was 410 days. One-, 2-, 3-, 4- and 5-year survival rates were 62%, 24%, 14%, 9% and 6%, respectively. As hematologic toxicities during chemoradiation, 35.1% with grade III/IV neutropenia and 18.9% with grade III/IV thrombocytopenia were noted. Grade II/III radiation pneumonitis and radiation esophagitis were noted in 5/1 and 13/1 patients (15.2%/ 3.0% and 39.4%/3.0%), respectively. One patient died of septicemia during chemoradiation.
CONCLUSION
The concurrent EP and TRT after 2 cycles of EP was feasible in limited stage small cell lung cancer. Further study is required for the indentification of optimum timing of TRT during combination chemotherapy.

Citations

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Effect of early chemoradiotherapy in patients with limited stage small cell lung cancer
In-Bong Ha, Bae-Kwon Jeong, Hojin Jeong, Hoon-Sik Choi, Gyu-Young Chai, Myoung-Hee Kang, Hoon Gu Kim, Gyeong-Won Lee, Jae-Beom Na, Ki-Mun Kang
Radiation Oncology Journal.2013; 31(4): 185. CrossRef

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Salvage Treatment for Advanced Gastric Cancer Using FEP (5-FU, Etoposide, Cisplatin) Combination Chemotherapy: Je Hyuk Chung, Yee Zee Bae, Sung Hyun Kim, Chang Hoon Moon, Jun Young Chung, Hyuk Chan Kwon, Jae Seok Kim, Hyo Jin Kim; Cancer Res Treat. 2002;34(5):382-387. Published online October 31, 2002; DOI: https://doi.org/10.4143/crt.2002.34.5.382

Abstract PDF

PURPOSE
There is no effective treatment for patients with advanced gastric cancer having failed to respond to first line chemotherapy. The aim of this study was to evaluate the therapeutic activity, and safety, of a FEP regimen in patients with a recurrence of, or metastatic, gastric cancer that had been unresponsive to primary chemotherapy.
MATERIALS AND METHODS
Recurred or metastatic gastric cancer patients that did not respond to a 5-fluorouracil based regimen were entered into this trial. The patients were treated with FEP (5-FU, etoposide and cisplatin) as salvage chemotherapy. The treatment regimen was 5-FU (900 mg/m2/day) by continuous infusion for 3 days, etoposide (90 mg/m2/day) on days 1, 2 and 3, and cisplatin (60 mg/m2/day) on day 2. This treatment was repeated every 3 weeks.
RESULTS
Between December 1997 and October 2001, 28 patients were enrolled to the study. The response rate was 32.1% (95% CI 15.5~57.8%). The median times to progression and survival duration were 23~33 weeks, respectively. Among a total of 187 cycles of chemotherapy, the grade 3 and 4 hematological toxicities were leukopenia (6.4%), thrombocytopenia (1.6%), and grade 3 non-hematological side effects of nausea/vomiting (17.9%).
CONCLUSION
FEP combination chemotherapy seems to be an effective treatment regimen for gastric cancer as salvage chemotherapy. To confirm these results, large scale of clinical trials will be required.

Citations

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Anticancer Effect of a Novel Octahydropyrazino[2,1-a:5,4-a′]diisoquinoline Derivative and Its Synergistic Action with Nigella sativa in Human Gastric Cancer Cells
Anna Czajkowska, Agnieszka Gornowicz, Natalia Pawłowska, Robert Czarnomysy, Jolanta Nazaruk, Wojciech Szymanowski, Anna Bielawska, Krzysztof Bielawski
BioMed Research International.2017; 2017: 1. CrossRef
The Efficacy of Docetaxel and Cisplatin Combination Chemotherapy for the Treatment of Advanced Gastric Cancer after Failing to 5-Fluorouracil Based Chemotherapy
Sang-Joon Shin, Min-Kyoung Kim, Kyung-Hee Lee, Myung-Soo Hyun, Sang Woon Kim, Sun Kyo Song, Sung-Hwa Bae, Hun-Mo Ryoo
Cancer Research and Treatment.2004; 36(6): 367. CrossRef

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Phase II Study of Topotecan and Etoposide as Second-line Treatment in Chemotherapy-refractory Small-cell Lung Cancer: Chul Kim, Joo Hyuk Sohn, Joo Hang Kim, Se Kyu Kim, Young Sam Kim, Joon Chang, Jae Yong Cho; Cancer Res Treat. 2002;34(5):334-338. Published online October 31, 2002; DOI: https://doi.org/10.4143/crt.2002.34.5.334

Abstract PDF

PURPOSE
Refractory small-cell lung cancer (SCLC) has a poor prognosis, and current salvage chemotherapy for refractory SCLC, such as CAV (cyclophosphamide, adriamycin, vincristine) or topotecan, has an unsatisfactory outcome, with a response rate and overall survival of less than 10% and 6 months, respectively. This phase II study evaluated the role of topotecan combined with etoposide in SCLC patients that have progressed, or relapsed, within 3 months following completion of the initial chemotherapy.
MATERIALS AND METHODS
Twenty-seven patients were entered into this study. Eligible patients had an ECOG performance status of less than, or equal to, 2, at least one bidimensionally measurable lesion and adequate end organ function. IV topotecan, 1.0 mg/m2/d for 5 consecutive days, and etoposide, 100 mg/m2/d through days 1 to 3, were administered every 3 weeks until disease progression or undue toxicity.
RESULTS
The major toxicity was myelosuppression. Grade 3/4 anemia, granulocytopenia, and thrombocy-topenia occurred in 14.2, 34.8, and 27.3% of cycles, respectively. There was no treatment-related death, and other non-hematologic toxicities were generally mild. Four patients achieved partial responses, with a response rate RR of 14.8%. The progression-free survival PFS ranged from 1 to 7 months, with a median of 2.0 months (95% confidence interval 1.22~2.78 months). Twenty-five patients died, with a median overall survival of 5.5 months (ranging from 1 to 21 months, 95% CI 4.32~6.68 months), and the 6-month survival rate was 32.1% (95% confidence interval 14.4~49.8%).
CONCLUSION
The combination of topotecan and etoposide chemotherapy showed a modest response rate, but failed to prolong survival of refractory SCLC patients compared to topotecan monotherapy.

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Real-World Outcomes with Lurbinectedin in Second Line and Beyond for Extensive Stage Small Cell Lung Cancer in Korea
Joo Sung Shim, Youhyun Kim, Taeho Yuh, Jii Bum Lee, Hye Ryun Kim, Min Hee Hong, Byoung Chul Cho, Sun Min Lim
Lung Cancer: Targets and Therapy.2024; Volume 15: 149. CrossRef

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MINE (mesna, ifosfamide, mitoxantrone, etoposide) Chemotherapy as a Treatment of Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma: Seong Hoon Chang, Yang Soo Kim, Wan Kyu Eo; Cancer Res Treat. 2002;34(2):145-152. Published online April 30, 2002; DOI: https://doi.org/10.4143/crt.2002.34.2.145

Abstract PDF

PURPOSE
The prognosis of non-Hodgkin's lymphoma (NHL) is disappointing for patients who experience primary treatment failure or relapse after an initial response. Patients in relapse may respond again to chemotherapy, however the time to disease progression becomes shorter and eventually the disease becomes resistant. The aim of this study was to evaluate the efficacy and safety of the MINE regimen in the treatment of patients with relapsed or refractory NHL. Material and Methods: Forty-three pretreated patients with a median age of 56 years were enrolled into the study between October 1995 and June 2000. Most patients (60.5%) had a performance status of 0 to 1, and a diffuse large cell subtype (55.8%). Seventy-four percent of patients had stage III or IV disease at the start of MINE treatment. Eighteen (41.9%) patients had complete response, 5 (11.6%) had partial response, and 20 (46.5%) had failed to respond to prior therapy. Ifosfamide 4 g/m2 was divided over 3 days and administered IV over a 1 hour period. Mitoxantrone 8 mg/m2 was administered as a short IV infusion on day 1. Etoposide (65 mg/m2/day) was infused over 1 hour on days 1 to 3. A total of 144 cycles was administered, with a mean of 3.34 cycles per patient (range, 1-8). The mean relative dose intensity was 87.4%.
RESULTS
1) Nine patients achieved a complete response and nine patients achieved a partial response, resulting in an overall response rate of 43.8% of the 41 assessable patients. 2) The median survival time was 6 months (95% CI, 4 to 8 months), and the median time to failure was 5 months (95% CI, 3 to 7 months). 3) A statistically significant association with complete response rates was found for complete response to prior therapy (p=0.049). The significant factors for overall survival were a complete response after MINE chemotherapy and serum 2-microglobulin (p=0.003, p=0.012, respectively). The significant factors for time to treatment failure were a complete response after MINE chemotherapy and serum 2-microglobulin (p=0.003, p=0.044, respectively). 4) The main result of toxicity of MINE was bone marrow suppression.
CONCLUSION
The response to MINE chemotherapy and serum 2-microglobulin were both independent prognostic factors for overall survival and time to treatment failure. As the median time to treatment failure for complete responses was 14 months, the best use of this regimen could be in a strategy that includes prompt consolidation of a complete response with intense chemotherapy, with or without hematopoietic stem cell rescue.

Citations

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Clinical feasibility of oral low-dose etoposide and sobuzoxane for conventional chemotherapy–intolerant lymphoma patients
Akihiro Ohmoto, Shigeo Fuji
Expert Review of Anticancer Therapy.2021; 21(7): 715. CrossRef

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Expression of Cell Cycle Regulatory and Apoptosis-related Proteins in Etoposide-treated Human Skin Fibroblast: Jae We Cho, Min Ho Suh; J Korean Cancer Assoc. 2001;33(1):77-83.

Abstract PDF: PURPOSE
This study was designed to investigate effect of the etoposide on expression of cell cycle regulatory proteins and apoptosis-related proteins in human skin fibroblast (HSF).
MATERIALS AND METHODS
HSF cells were treated with etoposide. After treatment, expression patterns of cell cycle regulatory proteins and apoptosis-related proteins were analyzed by using Immunoprecipitation-Western blot method and RT-PCR.
RESULTS
Immediately after etoposide treatment, E2F-1 was up- regulated following MDM2 down-regulation. After E2F-1 up-regulation, p53 and p21WAF1 level was markedly increased without or with mRNA up-regulation, respectively. Consistent with these results, cell cycles arrested in mainly G1 phase 24 hr after etoposide treatment. However, HSF cells progressed into apoptosis 72 hr after etoposide treatment. In this process, caspase-3 activation and Bax up-regulation were observed.
CONCLUSION
In early response of etoposide treatment, E2F-1 plays an important role in p53 accumulation through MDM2 down- regulation. The increased p53 induce an increase of p21WAF1 level through p21WAF1 mRNA up-regulation. However, after long term treatment of etoposide, HSF cells resulted in apoptotic cell death through caspase-3 activation and Bax up-regulation.

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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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Combination Chemotherapy with Etoposide, Doxorubicin, Cisplatin (EAP) for Recurred or Metastatic Gastric: Nam Kuk Cho, Tae Sik Choi, Yeon Hee Park, Seung Chul Lee, Young Jin Yuh, Sung Rok Kim; J Korean Cancer Assoc. 2000;32(3):524-530.

Abstract PDF: PURPOSE
We performed this study to evaluate the efficacy and the safety of EAP regimen as a second line therapy for the recurred or metastatic gastric cancer unresponsive to 5-fluorouracil based chemotherapy.
MATERIALS AND METHODS
Recurred or metastatic gastric cancer patients unresponsive to 5- fluorouracil based regimen were entered into this trial. They were treated by EAP chemotherpy which consisted of etoposide 40 mg/m2, doxorubicin 15 mg/m2 and cisplatin 25 mg/m2 IV during 3 days each every 3 weeks.
RESULTS
From December 1994 to March 1998, Eighteen patients were enrolled in this protdegrees Col. Fourteen patients were evaluable for response. The overall response rate was 28.6% (95% CI: 11.7~56.7%). The median response duration was 21 weeks. The median survival for all enrolled patients was 28 weeks. The major toxicity was myelosuppression. Among total of 69 cycle che motherapy, WHO grade 3 or 4 granuldegrees Cytopenia and thrombdegrees Cytopenia were observed in 71.0% and 27.5%, respectively.
CONCLUSION
Second line therapy with EAP regimen was active for gastric cancer. Chemotherapy induced toxicities were moderate to severe.

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Combination Chemotherapy with VP - 16 , Ifosfamide , and Cisplatin ( VIP ) in the Advanced Non - Small Cell Lung Cancer: Yong Seon Cho, Si Young Kim, Jeong Hee Kim, Hwi Joong Yoon, Kyung Sam Cho; J Korean Cancer Assoc. 2000;32(1):86-92.

Abstract PDF: PURPOSE
We conducted a phase II study in previously untreated patients with unresectable stage IIIB or IV non-small cell lung cancer to evaluate the response rate and toxicity of the combination chemotherapy regimen of etoposide, ifosfamide and cisplatin. MATERIALS AND METHODS: From September 1993 to December 1996, twenty patients with advanced non-small cell lung cancer (stage IIIB 5 and IV 15) (squamous cell 8, adeno- carcinoma 12), were enrolled in this study. There were 13 (65%) males and 7 (35%) females, and median age of patients were 56 years (range: 34~66). Eighteen patients had performance status (ECOG) 0~1, two patients had performance status 2. Treatment was consisted of cisplatin (20 mg/m2 i.v., day 1~4), VP-16 (etoposide) (75 mg/m2 i.v., day 1~4), ifosfamide (1000 mg/m2 i.v., day 1~4) with mesna. This treatment was repeated every four weeks.
RESULTS
The overall response rate was 25%. Complete response rate was 5% (1/20) and partial response rate was 20% (4/20). The median cycle of response was 4 (2~6) cycles. The median overall survival time was 28 weeks (9~98 weeks). The median time to progression was 10 weeks (3~50 weeks). Toxicities were evaluated by WHO criteria. Toxicity > GradeIII included: leukopenia 1.6%, thrombocytopenia 3.2%, nausea and vomiting 15%, alopecia 30%, stomatitis 10%. These toxicities were tolerable and reversible.
CONCLUSION
VIP regimen was not superior to previous regimens for advanced non-small all lung cancer, and the toxicities were tolerable.

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Combination Chemotherapy with Cisplatin, Ifosfamide, and Etoposide in Small Cell Lung Cancer: In Keun Choi, Byung Soo Kim, Jae Jeong Shim, Sang Won Shin, Yeul Hong Kim, Kyung Ho Kang, Kwang Taek Kim, Jun Suk Kim, Young Ho Choi; J Korean Cancer Assoc. 1999;31(4):692-698.

Abstract PDF: PURPOSE
Although chemotherapy is considered as the mainstay of treatment for small cell lung cancer, long-term survival is not expected in the majority of patients. Until more effective drugs are developed, optimization of available chemotherapeutic regimens and the combination with radiotherapy will be required to improve the survival of small cell lung cancer patients. We conducted a phase II trial to evaluate the effect of a combination chemotherapy of cisplatin, ifosfamide, and etoposide.
MATERIALS AND METHODS
From January 1994 to December 1997, 34 untreated small cell lung cancer patients were enrolled in this study. The treatment schedule included etoposide 80 mg/m/day, ifosfamide 1.5 g/m'/day, cisplatin 20 mg/m/day iv continuous infusion on day 1-3. Cycles were repeated every 4 weeks.
RESULTS
The objective response rate was 58% [localized disease (LD), 100%; extensive disease (ED), 48%]. And complete remission rate was 19% (LD, 38%; ED, 13%). The median survival of all patients was 12 months (LD, 17 months; ED, 12 months). The median duration of response was 7 months. There was one treatment-related death. The hematologic toxicities were tolerable: Leukopenia greater than Grade III was 25%, and thrombocytopenia greater than Grade III was 6%. Nausea and vomiting were seen in most patients, but they were controllable.
CONCLUSION
The combination chemotherapy with cisplatin, ifosfamide, and etoposide as a first line therapy seemed effective with tolerable toxicity in patients with small cell lung cancer.

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Combination Chemotherapy with Etoposide, Ifosfamide, and Cisplatin (VIP) in Small Cell Lung Cancer: Goon Jae Cho, Joo Seop Chung, Ihm Soo Kwak, Ha Yeon Rha; J Korean Cancer Assoc. 1999;31(3):539-547.

Abstract PDF: PURPOSE
Combination chemotherapy has shown promising activity in small cell lung cancer (SCLC). This study was perfonned to determine the efficacy of the combination chemotherapy with etoposide, ifosfamide and cisplatin (VIP) in previously untreated patients with SCLC.
MATERIALS AND METHODS
Patients with SCLC were treated with etoposide (75 mg/m iv. D1-4), ifosfamide (1200 mg/m iv. Dl-4 with mesna) and cisplatin (20 mg/m iv. D1-4). The treatment was repeated every 3 weeks for 6 cycles in principle. Thoracic radiotherapy was administered to patients with limited disease (LD) of SCLC after initial 2 or 3 cycles of chemotherapy subsequently. Praphylactic cranial irradiation (PCI) was given to complete responders of SCLC.
RESULTS
From April 1996 through June 1998, 42 patients were included, but 32 were eligible for the study (4 refused of treatment, 2 lost in follow-up, and 4 combined with other disease). The median age was 62 years (range, 42-74). Twelve patients had LD and 20 patients were with extended disease (ED). Complete response (CR) rate was 34% (LD 58%, ED 20%) and overall response rate was 72% (LD 83%, ED 65%). The median duration of response was 28 weeks (38 weeks in LD, 24 weeks in ED, P=0.016) With the median follow-up period of 65 weeks (6-134 weeks), overall median survival was 43 weeks (56 weeks in LD, 34 weeks in ED, P 0.001), and the median disease free survival (DFS) of eleven CR patients was 16 weeks. Stage, performance, and LDH level were significant prognostic factom (P 0.011, 0.002, 0.043, respectively), but sex and age did not affect the outcome significantly. The hematologic side effects (WHO grade 2) of evaluable 152 cycles of chemotherapy were leukopenia (53%), thrombocytopenia (31%) and anemia (16%); and nonhematologic side effects (WHO grade >2) were alopecia (84%), nausea/vomiting (45%) and stomatitis (19%).
CONCLUSION
It appears that VIP combination chemotherapy is a safe, effective and well tolerated regimen for the patients with SCLC.

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A Phase 2 Study of VP-16 , Ifosfamide , and Cisplatin ( VIP ) Combination Chemotherapy Plus Concurrent Thoracic Irradiation for Limited Small Cell Lung Cancer: Seok Ah Im, Moon Hee Lee, Chul Won Jung, Dae Seog Heo, Yung Jue Bang, Young Soo Shim, Chan Il Park, Noe Kyeong Kim; J Korean Cancer Assoc. 1999;31(2):306-312.

Abstract PDF: PURPOSE
A phase II study of etoposide, ifosfamide, cisplatin combination chemotherapy and concurrent thoracic irradiation in patients with untreated limited small cell lung cancer (SCLC) was conducted to assess toxicities, response rate, response duration, and median survival.
MATERIALS AND METHODS
Patients with histologically confirmed SCLC with a ECOG criteria 2 and adequate renal function and bone marrow reserve were eligible. Each cycle consisted of VP-16 100 mg/m i.v, days 1-3, ifosfamide 1,200 mg/m i.v. days 1-3 with Mesna, and cisplatin 30 mg/m i.v. days 1-3. Cycles were repeated every 21 days. Concutrent thoracic itradiation was given as total 40-45 Gy for 4-5 weeks beginning within 24 hours of the third cycle. Patients with complete remission received prophylactic cranial irradiation after the 6th cycle.
RESULT
Forty two patients with limited SCLC were treated at Seoul National University Hospital between December 1993 and August 1996. Three patients were not evaluable because of lost to follow up (2 patients) and one treatment-related early death. Of 39 evaluable patients, responses were seen in 38 (97%) patients including 22 (56%) complete responses and 16 (41%) partial responses. The median remission duration was 65 wks. The median disease free survival was 60 wks. The median overall survival was not reached and 2-year survival was 69% with median duration of follow up of 63.5 wks. Hematologic side effects (WHO Gr>III/IV) of evaluable 228 cycles of chemotherapy were leukopenia in 34%, thrombocytopenia in 16%. One patient expired after prolonged leukopenia and sepsis. Nonhematologic side effects (WHO Gr>II) included nausea and vomiting (17%) and peripheral neuropathy (2%).
CONCLUSION
VIP combination chemotherapy with concurrent thoracic irradiation is effective and tolerable in limited SCLC.

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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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A Phase 2 Trial of PEF ( Cispatin , Etoposide , 5-Fluorouracil ) Chemotherapy for Metastatic Stomach Cancer: Yoon Koo Kang, Kwang Seob Yum, Hee Jun Cho, Jhin Oh Lee, Taik Koo Yun; J Korean Cancer Assoc. 1998;30(5):900-906.

Abstract PDF: PURPOSE
To determine the activity and toxicities of PEF (Cisplatin, Etoposide, 5-Fluorouracil) chemotherapy for stomach cancer.
MATERIALS AND METHODS
Patients with previously untreated metastatic stomach cancer were treated with PEF regimen which consisted of cisplatin (20 mg/m2 i.v. days 1~5), etoposide (100 mg/m2 i.v. days 1, 3, 5), and 5-fluorouracil (5-FU)(800 mg/m2 i.v. infusion for 12 hours days 1~5). Chemotherapy was repeated every 3 weeks until disease progressed or toxicities were intolerable.
RESULTS
Between May 1989 and July 1990, 40 patients were enrolled in this protocol. Twelve patients were lost to follow up after one cycle of chemotherapy and inevaluable. After 2~8 cycles (median 3) of chemotherapy, 20 out of 28 evaluable patients showed objective responses without any complete response, making the response rate 71% (95% confidence interval: 54~89%). The responses lasted from 4+ to 39 weeks (median: 38 weeks). The overall survival of total evaluable patients was 4+ ~50+ weeks (median 38 weeks). Among total 109 cycles of chemotherapy, cycles were delayed or doses were reduced in 48 cycles (44%) because of leukopenia (in 61 cycles: 56%) and/or thrombocytopenia (in 14 cycles: 13%). However, there was no treatment-related death. Nausea/vomiting and alopecia were experienced in most of patients. The stomatitis was experienced in 7 patients (25%) but completely reversible. In contrast, the peripheral neuropathy which developed in 4 patients (14%) after 5 cycles of chemotherapy was not reversible.
CONCLUSION
The PEF regimen was active and tolerable in stomach cancer.

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Restoration of Wild - type p53 Induces Chemo-sensitization in the Gastric Cancer Cell Line with Mutant p53: Ho Young Maeng, Sun Young Rha, Byung Soh Min, Yong Bae Kim, Hyun Joo Kwak, Tae Soo Kim, Kyu Hyun Park, Nae Choon Yoo, Ho Young Lim, Jin Hyuk Choi, Joo Hang Kim, Jae Kyung Roh, Jin Sik Min, Byung Soo Kim, Hyun Cheol Chung; J Korean Cancer Assoc. 1998;30(3):497-507.

Abstract PDF: PURPOSE
It has been theorized that p53 may be involved in the sensitivity to chemotherapeutic agents. We evaluated the chemosensitivity of wild p53 after transduction into gastric cancer cell lines with mutant p53.
MATERIALS AND METHODS
YCC-3(parent cell line with mutant p53), YCC-3v(parent cell line transduced with vector alone) and YCC-3C3(clone with wild p53) cell lines were used in this study. p53 protein expression was measured by ELISA assay. Tumorigenicity and drug sensitivity were evaluated by soft agar and proliferation assay, respectively. Cell cycle analysis was performed by flowcytometry. Telomerase activity was measured by TRAP assay and terminal restriction fragment(TRF) length was measured after Southern blot analysis.
RESULTS
Even though p53 production from the YCC-3C3 cell line was three times higher than those of YCC-3 and YCC-3v cell lines, the cell cycle was the same in these three cell lines. In the YCC-3C3 cell line, drug sensitivity to etoposide and cisplatin was increased when we compared it to those of the YCC-3v cell line(etoposide, 50% versus 83%; cisplatin, 67% versus 83%). However, there was no chemo-sensitization effect with vincristine, vinblastine and carboplatin. After exposure to cisplatin, a G0/G1 check-point effect was found in the YCC-3C3 cell line, but not in the YCC-3v cell line. No differences were found in telomerase activity, TRFs length or DNA fragmentation between the YCC-3v and YCC-3C3 cell lines after cisplatin treatment.
CONCLUSION
Wild-type p53 gene transduction in the gastric cancer cell line induced sensitization to the cytotoxicity of etoposide and cisplatin. This suggests the possible application of combined chemo-gene therapy with an EP regimen and wild-type p53 in gastric cancer patients with p53 mutation.

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Results of CHOP-Bleo / CMED Alternating Chemotherapy for Aggressive Non - Hodgkin's Lymphoma: Suk Jin Kim, In Keun Choi, Sang Chul Oh, Jae Hong Seo, Byung Soo Kim, Sang Won Shin, Yeul Hong Kim, Jun Suk Kim; J Korean Cancer Assoc. 1998;30(2):350-356.

Abstract PDF: PURPOSE
To assess the efficacy and toxicity of a new protocol that consists of CHOP- Bleo alternated with a new regimen of Cyclophosphamide, methotrexate, etoposide, and dexamethasone(CMED) for aggressive Non-Hodgkin's Lymphoma(NHL). PATIENTS AND METHODS: Between January 1991 and December 1996, forty-six patients with Ann Arbor stages II-IV aggressive NHL were treated with alternating cycles of CHOP-Bleo and CMED for a total of 12 cycles. All eligible patients were evaluated for response, disease-free survival, and overall survival.
RESULTS
Twenty-two patients(47.8%) achieved a complete response and overall response rate was 83.9%. The range of survival duration was 1-68+months and the median survival time was 42 months. Overall 3-year survival rate was 54%. The range of disease-free survival time was 6-63+months and 3-year disease-free survival rate was 61%. The most common hematologic toxicity was leukopenia and the incidence of severe leukopenia(<1,000/mm3) was 11%. And alopecia(84.8%) was the most common non-hematologic toxicity.
CONCLUSION
The results of CHOP-Bleo/CMED alternating chemotherapy for patients with aggressive Non-Hodgkin's Lymphoma is not superior to other results of previous studies. Therefore further study will be warranted to determine clinical effectiveness of alternating chemotherapy.

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Combination Chemotherapy with Cisplatin , Etoposide , and Ifosfamide ( PIE ) in the Advanced Non - Small Cell Lung Cancer: Sang Won Shin, Byung Soo Kim, Jae Jung Shin, Yeul Hong Kim, Kyung Ho Kang, Young Ho Choi, Kwang Tak Kim, Jun Suk Kim; J Korean Cancer Assoc. 1998;30(2):225-230.

Abstract PDF: PURPOSE
Combination chemotherapy with cisplatin and etoposide have been considered as one of the chemotherpy regimen for non small cell lung cacer(NSCLC) with the response rate of 20~40%. Ifosfamide is one of the most active agent against NSCLC. And so, we initiated a phase II trial for advanced NSCLC to determine the effect of PIE(cisplatin, ifosfamide, etoposide) regimen.
MATERIALS AND METHODS
36 patients with inoperable non-small cell lung cancer who had no prior systemic chemotherapy were treated with combined ifosfamide (1,800 mg/m2 plus mesna 1,100 mg/m2 by intravenous continuous infusion daily for 3 days) with cisplatin (20 mg/m2 intravenous for 3 days) and etoposide (80 mg/m2 intravenous for 3 days). We evaluated the response rate, survival and toxicities of these patients.
RESULTS
The objective response rate was 28%(CR; 2/36, 6%, PR; 8/36, 22%). Among 10 responders, 7 patients were in good ECOG performance status(0~1). The mean survival of all these patients were 43 weeks(8~141 weeks); the responding patients survived longer than the non-responders(median survival; 59 weeks vs 28 weeks, p<0.05). The toxicities of this regimen were acceptable without treatment related toxic death.
CONCLUSION
We concluded that PIE regimen is effective in the treatment of advanced non-small cell lung cancer with acceptable toxicities and long-term follow up is warranted.

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A Phase 2 Trial of EPOCH (Etoposide, Vincristine, Doxorubicin, Cyclophophamide and Prednisolone) Chemotherapy for Previously Treated Non - Hodgkin's Lymphoma: Baek Yeol Ryoo, Tae You Kim, Young Hyuk Im, Jhin Oh Lee, Taik Koo Yun, Keun Chil Park; J Korean Cancer Assoc. 1998;30(1):127-136.

Abstract PDF: PURPOSE
As a new strategy to modulate drug resistance in the treatment of relapsed or refractory non-Hodgkin's lymphoma(NHL), continuos infusion of drugs has been incorporated into the chemotherapy. We conducted a phase II study to determine the activity and safety of EPOCH (etoposide, vincristine, doxorubicin, cyclophosphamide, prednisolone) chemotherapy, in which the natursl products are administered as a continuous infusion, for previously treated NHL's of intermediate grade.
MATERIALS AND METHODS
EPOCH chemotherapy (etoposide 50 mg/m2/day 24 hour- continuous infusion, days 1~4, vincristine 0.4 mg/m2/day 24 hour-continuous infusion, days 1~4, doxorubicin 10 mg/m2/day 24 hour-continuous infusion, days 1~4, cyclophosphamide 750 mg/m2 i.v., day 5, prednisolone 60 mg/m2/day p.o. days 1-5) was given to eligible patients every 3 weeks and we assessed response and toxicity of the regimen.
RESULTS
Between June 1993 and December 1995, total 56 patients entered this trial and 49 were evaluable. The complete response rate was 41%(95% C.I.: 27-55%). After follow up of 9~50(median 38) months, progression free survival was 0~39+(median 7) months and the overall survival was 1~44+(median 14) months. The prognostic factor analyses showed that B symtoms and serum LDH level before treatment and response to previous treatment affected complete response rate, and patients' performance status and response to previous treatment affected progression free survival and overall survival. Toxicities of EPOCH regimen were leukopenia, stomatitis, nausea/vomiting and neurotoxicity, but they were tolerable. There was 1 case of treatment-related death due to sepsis. CONDUSION: EPOCH chemotherapy was safe and effective for the patients with relapsed NHL. However, the results of patients with NHL refractory to previous treatment were so poor that more intensive, novel treatment would be needed for this category of patients.

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Combination Chemotherapy with Etoposide, Ifosfamide, and Cisplatin (VIP) in Small Cell Lung Cancer: Mi Young Park, Joon Yeon Won, Kyung Tae Park; J Korean Cancer Assoc. 1997;29(6):1011-1021.

Abstract PDF: 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.

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Stability of Cisplatin and Etoposide in Normal Solution: Sang Cheul Oh, Young Mi Kim, Young Inn You, Song Ja Jo, Byung Soo Kim, Sang Won Shin, Yeul Hong Kim, Jun Suk Kim; J Korean Cancer Assoc. 1997;29(4):700-705.

Abstract PDF: PURPOSE
The cisplatin and etoposide had been reported to be an effective anti-tumor drug for small cell lung cancer, ovarian cancer, breast cancer and so on. The aim of this study was to evaluate the stability of cisplatin and etoposide in aqueous solution.
MATERIALS AND METHODS
Cisplatin 200 microgram/ml was prepared in 0.9% sodium chloride and stored in either glass bottle or polyvinyl chloride (pvc) bag and protected from light or exposed to fluorescent light. Etoposide solution was prepared in 0.9% sodium chloride, and contained in glass bottle. Precipitating concentration was achieved using 200 microgram/ml, 400microgram/ml, 600 microgram/ml, and 1000 microgram/ml of etoposide solution. Samples were stored at room temperature and visually inspected and assayed for etoposide and cisplatin content by high-performance liquid chromatography after 15 minutes, 2, 4, 8, 12, 16 and 24 hours of storage.
RESULT
1) Cisplatin concentration decreased less than 10% from initial concentration for 24 hours of storage, both in glass bottle and pvc bag. Stability of cisplatin 200 microgram/ml in both container were not different. and Condition of light exposure did not have significant effect on stability of cisplatin 200 microgram/ml in glass bottle. 2) The etoposide 200 microgram/ml was not precipitated and stable for 24 hours, but we could find the precipitates of etoposide with the concentration of 400 microgram/ml or higher for 24 hours.
CONCLUSION
Cisplatin 200 microgram/ml and etoposide 200 microgram/ml in 0.9% sodium chloride were stable at room temperature under room fluorescent light for 24 hours.

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Chemotherapy of Advanced Soft Tissue Sarcoma with Etoposide, Ifosfamide, and Cisplatin (VIP): Won Seog Kim, Kyung Hae Jung, Hyun Ah Kim, Sung Hyun Yang, Dae Seog Heo, Yung Jue Bang, Noe Kyeong Kim; J Korean Cancer Assoc. 1997;29(1):128-135.

Abstract PDF: PURPOSE
Soft tissue sarcomas are uncommon primary malignancies. So studies on the effective chemotherapy for soft tissue sarcomas are limited. We started this study to evaluate the effectiveness of VIP (etoposide, ifosfamide, cisplatin) combination chemotherapy for advanced soft tissue sarcomas.
MATERIALS AND METHODS
Thirty patients with recurrent or metastatic soft tissue sarcoma were treated with VIP combination chemotherapy between December 1989 and June 1996. Each patient was given etoposide 75 mg/m2, ifosfamide 1000 mg/m2, cisplatin 20 mg/m2 intravenously for five consecutive days every three weeks. Mesna (sodium-2-mercaptoethansulfonate) was given to avoid the urologic toxicity.
RESULTS
Twenty-eight of 30 patients were evaluable for response, and among the 28 evaluable patients, there were 9 partial response (32%). Duration of response in 9 responders ranged from 4.1 to 16.2 months (median 8.8 months). Overall survival ranged from 1.7 to 41.5 months (median 11 months) and survival was better for patients with partial response (median survival 14.8 months vs. 9.7 months with stable disease vs. 5.1 months with progressive disease p=0.0006). Nausea and vomiting was noted in more than 90% of cycles, but was markedly severe in only 4%. Leukopenia was noted in 60% of cycles, including 11% of cycles with counts <2,000/mm3. There was no treatment related death, but we had to stop chemotherapy in 2 patients due to leukopenia (1 patient) and neurotoxicity (1 patient).
CONCLUSION
Combination of etoposide, ifosfamide, and cisplatin was fairly active for advanced soft tissue sarcoma, with myelosuppresion and peripheral neuropathy being the most serious toxicities.

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A Phase 2 Study of VP-16 , Ifosfamide Cisplatin ( VIP ) Combination Chemotherapy for Small Cell Lung Cancer: Rok Yun Lee, Young Suk Park, Yun Chang Han, Ho Joong Kim, In Gyu Hyun, Ki Suk Jung, Jung Ae Rhee, In Sook Woo, Young Iee Park, Keun Chil Park, Duk Jhe Shun, Sang Gyu Choi, Do Hoon Oh, Hoon Sik Bae; J Korean Cancer Assoc. 1995;27(4):620-630.

Abstract PDF: We conducted a phase II trial combining etoposide(VP-16), ifosfamide(IFM), and cisplatin (DDP) in previously untreated patients with histologicaliy confirmed small cell lung cancer (SCLC). Each cycle consisted of VP-16 100mg/m(2) i.v. days 1-3, IFM 1,000mg/m i.v. days 1-2 with mesna, and DDP 100mg/m(2) i.v. day 1. Cycles were repeated at 3 week intervals. Patients of limited SCLC received chest irradiation concurrently with the third cycle of VIP chemotherapy. Patients with complete remission received prophylactic cranial irradiation after the 6th cycle of chemotherapy. Thirty-seven patients were enrolled. Ages ranged from 34 to 76(median 61 years); 32 were male, and 5 female. Nineteen patients had limited disease(LD) and 18 extensive disease(ED). Three patients were not evaluable because of lost to follow up(2 patients) and early death(l patient). Of 34 evaluable patients, 13 patients(LD; 12, ED; I) had complete re- missions, 19 patients(LD: 6,ED; 13) had partial remissions and overall remission rate was 94 %. The median remission duration was 8.6 months(LD; 12.5months, D; 5.1months)..Disease free survival was 14.5 months in patients achieved complete remission. The median dura- tion of follow-up was 21 months (1 to 39 months), and overall median survival was 12.8 months(16.1 months for LD, 8.2 months for ED). Hematologic side effects(WHO Gr>=2) of evaluable 168 cycles of chemotherapy were anemia in 10 occassions(6%), leukopenia in 35 occassions(21%), thrombocytopenia in 27 occassions(16%). Nonhematologic side effects(WHO Gr>=2) included alopecia(91%), nausea and vomiting (80%), peripheral neuropathies (31%), and stomatitis (11%). In conclusion, VIP combination chemotherapy seems to be a safe, effective, and well-tolerated regimen in SCLC.

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