Cancer Research and Treatment

Original Articles

Modified MVAC as a Second-Line Treatment for Patients with Metastatic Urothelial Carcinoma after Failure of Gemcitabine and Cisplatin Treatment: Jung Hyun Lee, Sung Gu Kang, Seung Tae Kim, Seok Ho Kang, In Keun Choi, Young Je Park, Sang Chul Oh, Deuk Jae Sung, Jae Hong Seo, Jun Cheon, Sang Won Shin, Yeul Hong Kim, Jun Suk Kim, Kyong Hwa Park; Cancer Res Treat. 2014;46(2):172-177. Published online April 15, 2014; DOI: https://doi.org/10.4143/crt.2014.46.2.172

Purpose

There is no established standard second-line chemotherapy for patients with advanced or metastatic urothelial carcinoma (UC) who failed gemcitabine and cisplatin (GC) chemotherapy. This study was conducted in order to investigate the efficacy and toxicity of modified methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) in patients with metastatic UC previously treated with GC.

Materials and Methods

We retrospectively analyzed 28 patients who received modified MVAC between November 2004 and November 2012. All patients failed prior, first-line GC chemotherapy.

Results

The median age of patients was 64.0 years (range, 33.0 to 77.0 years), and 23 (82.1%) patients had an Eastern Cooperative Oncology Group performance status of 0 or 1. The overall response rate and the disease control rate were 36.0% and 64.0%, respectively. After a median follow-up period of 38 weeks (range, 5 to 182 weeks), median progression free survival was 21.0 weeks (95% confidence interval [CI], 6.3 to 35.7 weeks) and median overall survival was 49.0 weeks (95% CI, 18.8 to 79.3 weeks). Grade 3 or 4 hematological toxicities included neutropenia (n=21, 75.0%) and anemia (n=9, 32.1%). Grade 3 or 4 non-hematological toxicities did not occur and there was no treatment-related death.

Conclusion

Modified MVAC appears to be a safe and active chemotherapy regimen in patients with stable physical status and adequate renal function after GC treatment.

Citations

Citations to this article as recorded by

Chronological transition in outcome of second-line treatment in patients with metastatic urothelial cancer after pembrolizumab approval: a multicenter retrospective analysis
Teruki Isobe, Taku Naiki, Yosuke Sugiyama, Aya Naiki-Ito, Takashi Nagai, Toshiki Etani, Satoshi Nozaki, Keitaro Iida, Yusuke Noda, Nobuhiko Shimizu, Nami Tomiyama, Rika Banno, Hiroki Kubota, Shuzo Hamamoto, Ryosuke Ando, Noriyasu Kawai, Takahiro Yasui
International Journal of Clinical Oncology.2022; 27(1): 165. CrossRef
SIU-ICUD recommendations on bladder cancer: systemic therapy for metastatic bladder cancer
Axel S. Merseburger, Andrea B. Apolo, Simon Chowdhury, Noah M. Hahn, Matthew D. Galsky, Matthew I. Milowsky, Daniel Petrylak, Tom Powles, David I. Quinn, Jonathan E. Rosenberg, Arlene Siefker-Radtke, Guru Sonpavde, Cora N. Sternberg
World Journal of Urology.2019; 37(1): 95. CrossRef
Efficacy of Different Second-line Therapy Regimens in Metastatic Urothelial Carcinoma
Lukas Barwitz, Anne Berger, Stefanie Zschaebitz, Max Jenzer, Cathleen Nientiedt, Stefan Duensing, Dirk Jäger, Dogu Teber, Markus Hohenfellner, Carsten Grüllich
The Open Urology & Nephrology Journal.2017; 10(1): 52. CrossRef
Cisplatin- Versus Non–Cisplatin-based First-Line Chemotherapy for Advanced Urothelial Carcinoma Previously Treated With Perioperative Cisplatin
Jennifer A. Locke, Gregory Russell Pond, Guru Sonpavde, Andrea Necchi, Patrizia Giannatempo, Ravi Kumar Paluri, Guenter Niegisch, Peter Albers, Carlo Buonerba, Giuseppe Di Lorenzo, Ulka N. Vaishampayan, Scott A. North, Neeraj Agarwal, Syed A. Hussain, Sum
Clinical Genitourinary Cancer.2016; 14(4): 331. CrossRef
Second Line Chemotherapy for Advanced and Metastatic Urothelial Carcinoma: Vinflunine and Beyond—A Comprehensive Review of the Current Literature
Christoph Oing, Michael Rink, Karin Oechsle, Christoph Seidel, Gunhild von Amsberg, Carsten Bokemeyer
Journal of Urology.2016; 195(2): 254. CrossRef
Predicting the response of patients with advanced urothelial cancer to methotrexate, vinblastine, Adriamycin, and cisplatin (MVAC) after the failure of gemcitabine and platinum (GP)
Ki Hong Kim, Sung Joon Hong, Kyung Seok Han
BMC Cancer.2015;[Epub] CrossRef

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Association of Single Nucleotide Polymorphisms in PIM-1 Gene with the Risk of Korean Lung Cancer: Dae Sik Kim, Jae Sook Sung, Eun Soon Shin, Jeong-Seon Ryu, In Keun Choi, Kyong Hwa Park, Yong Park, Eui Bae Kim, Seh Jong Park, Yeul Hong Kim; Cancer Res Treat. 2008;40(4):190-196. Published online December 31, 2008; DOI: https://doi.org/10.4143/crt.2008.40.4.190

Abstract PDF PubReader ePub

Purpose

The expression of the PIM-1 gene, which is a proto-oncogene that encodes a serine/threonine kinase, is associated with multiple cellular functions such as proliferation, differentiation, apoptosis and tumorigenesis. In particular, several studies have reported that the PIM-1 gene is associated with the development of lymphoma, leukemia and prostate cancer. Therefore, this study was conducted to evaluate the association between the single nucleotide polymorphisms in the PIM-1 gene and the risk of lung cancer occurrence in the Korean population.

Materials and Methods

To evaluate the role of the PIM-1 gene in the development of lung cancer, the genotypes of the PIM-1 gene were determined in 408 lung cancer patients and 410 normal subjects.

Results

We found that the T-C-T-C haplotypes of the PIM-1 gene (-1196 T>C, IVS4 +55 T>C, IVS4 +1416 T>A and +3684 C>A) were associated with an increased risk of lung cancer [adjusted odds ratio (aOR): 3.98; 95% CI: 1.24~12.75, p-value: 0.020]. In particular, these haplotypes showed an increased risk of lung cancer in males (aOR: 5.67; 95% CI: 1.32~24.30, p-value: 0.019) and smokers (aOR: 7.82; 95% CI: 1.75~34.98, p-value: 0.007).

Conclusions

The present results suggest that the T-C-T-C haplotype of the PIM-1 gene could influence the risk of developing smoking-related lung cancer in the Korean population. Additional functional studies with an larger sample sized analysis are warranted to reconfirm our findings.

Citations

Citations to this article as recorded by

A review on structure-function mechanism and signaling pathway of serine/threonine protein PIM kinases as a therapeutic target
Ajaya Kumar Rout, Budheswar Dehury, Satya Narayan Parida, Sushree Swati Rout, Rajkumar Jena, Neha Kaushik, Nagendra Kumar Kaushik, Sukanta Kumar Pradhan, Chita Ranjan Sahoo, Ashok Kumar Singh, Meenakshi Arya, Bijay Kumar Behera
International Journal of Biological Macromolecules.2024; 270: 132030. CrossRef
Impact of Pim1 mutations on the survival outcomes of patients with breast cancer: Insights from a clinical study
Syed Sultan Beevi, Kavitha Anbrasu, Vinod Kumar Verma, Nagesh Kishan Panchal, Krishna Kiran Kannepalli, Raghu Ram Pillarisetti, Sailaja Madigubba, Jyotsana Dwivedi, Neha Damodar, Radhika Chowdary Darapuneni
Human Gene.2024; 40: 201295. CrossRef
HCG11 inhibits salivary adenoid cystic carcinoma by upregulating EphA2 via binding to miR-1297
Shujuan Yan, Meng Wang
Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology.2023; 135(2): 257. CrossRef
Therapeutic targeting of PIM KINASE signaling in cancer therapy: Structural and clinical prospects
Aanchal Rathi, Dhiraj Kumar, Gulam Mustafa Hasan, Mohammad Mahfuzul Haque, Md Imtaiyaz Hassan
Biochimica et Biophysica Acta (BBA) - General Subjects.2021; 1865(11): 129995. CrossRef
Loss of PIM1 correlates with progression and prognosis of salivary adenoid cystic carcinoma (SACC)
Jiajie Xu, Xin Zhu, Qingling Li, Chao Chen, Zhenying Guo, Zhuo Tan, Chuanming Zheng, Minghua Ge
Cancer Cell International.2018;[Epub] CrossRef
PIM Kinase as an Executional Target in Cancer
Xinning Zhang, Mengqiu Song, Joydeb Kumar Kundu, Mee-Hyun Lee, Zhen-Zhen Liu
Journal of Cancer Prevention.2018; 23(3): 109. CrossRef
HistoneH3 demethylase JMJD2A promotes growth of liver cancer cells through up-regulating miR372
Jiahui An, Jie Xu, Jiao Li, Song Jia, Xiaonan Li, Yanan Lu, Yuxin Yang, Zhuojia Lin, Xiaoru Xin, Mengying Wu, Qidi Zheng, Hu Pu, Xin Gui, Tianming Li, Dongdong Lu
Oncotarget.2017; 8(30): 49093. CrossRef
Expressions of osteopontin (OPN), ανβ3 and Pim-1 associated with poor prognosis in non-small cell lung cancer (NSCLC)
Yi Jin, Da-yue Tong, Lu-ying Tang, Jian-ning Chen, Jing Zhou, Zhi-ying Feng, Chun-kui Shao
Chinese Journal of Cancer Research.2012; 24(2): 103. CrossRef
Overexpression of Osteopontin, αvβ3 and Pim-1 Associated with Prognostically Important Clinicopathologic Variables in Non-Small Cell Lung Cancer
Yi Jin, Da-yue Tong, Jian-ning Chen, Zhi-ying Feng, Jian-yong Yang, Chun-kui Shao, Jia-ping Li, Rossella Rota
PLoS ONE.2012; 7(10): e48575. CrossRef
No Association between PIK3CA Polymorphism and Lung Cancer Risk in the Korean Population
Jae-Sook Sung, Kyong-Hwa Park, Seung-Tae Kim, Jae-Hong Seo, Sang-Won Shin, Jun-Suk Kim, Yeul-Hong Kim
Genomics & Informatics.2010; 8(4): 194. CrossRef

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Clinical Factors Related to Suspected Second Primary Lung Cancer Development in Patients with Head and Neck Cancer: Eui Bae Kim, Yong Park, Seh Jong Park, Dae Sik Kim, Jee Won Kim, Hee Yun Seo, Hwa Jung Sung, In Keun Choi, Kyong Hwa Park, Sang Cheul Oh, Chul Won Choi, Byung Soo Kim, Yeul Hong Kim, Jun Suk Kim, Sang Won Shin, Chul Yong Kim, Kwang-Yoon Jung; Cancer Res Treat. 2008;40(4):178-183. Published online December 31, 2008; DOI: https://doi.org/10.4143/crt.2008.40.4.178

Abstract PDF PubReader ePub

Purpose

The rate of second primary lung cancer development for patients with head and neck cancer (HNC) has been noted. The aim of our study was to evaluate the incidence and clinical features of suspected second primary lung cancer that developed in patients with primary HNC.

Materials and Methods

We conducted a retrospective study of 469 patients who were newly diagnosed with HNC at the Korea University Medical Center between January 2000 and December 2006.

Results

A total of 469 patients were included (389 men and 80 women). Eighteen patients (3.8%) had suspected second primary lung cancers. Statistically significant clinical variables for lung cancer development included the origin site for the primary HNC (oro-hypopharynx and larynx) (p=0.048), abnormal chest x-ray findings (p=0.027) and the histological HNC type (squamous cell carcinoma) (p=0.032). When the second primary lung cancers were combined with HNCs, the adjusted overall survival of patients with a second primary lung cancer was 16 months (p<0.001).

Conclusions

Considering the relative risk factors for a second primary lung cancer developing in patients with HNC, advanced diagnostic tools, such as chest CT or PET CT scan, should be applied for the early detection of a second primary lung cancer.

Citations

Citations to this article as recorded by

Bridging the gap between tumor evolution and clonality diagnostics in multiple lung carcinomas
Jurriaan Janssen, Michael Allgäuer, Bauke Ylstra, Swip Draijer, Yongsoo Kim, Jan Budczies, Daniel Kazdal, Albrecht Stenzinger, Martina Kirchner, Teodora Radonic
Seminars in Cancer Biology.2026; 122: 1. CrossRef
Long-Term Survival in Metachronous Primary Malignancies: Stage III Nasopharyngeal Cancer and Stage IV Non-Small-Cell Lung Cancer
Gabriela Rahnea-Nita, Alexandru Nechifor, Mihai-Teodor Georgescu, Dorel Firescu, Adrian-Cornel Maier, Radu-Valeriu Toma, Valentin Titus Grigorean, Liliana-Florina Andronache, Roxana-Andreea Rahnea-Nita, Ionut Simion Coman, Laura-Florentina Rebegea
Journal of Clinical Medicine.2025; 14(10): 3299. CrossRef
African American race as a risk factor associated with a second primary lung cancer after initial primary head and neck cancer
Yusra F. Shao, Seongho Kim, John D. Cramer, Dina Farhat, Jeffrey Hotaling, Syed Naweed Raza, George Yoo, Ho‐sheng Lin, Harold Kim, Ammar Sukari, Misako Nagasaka
Head & Neck.2022; 44(10): 2069. CrossRef
Should fluorodeoxyglucose positron emission tomography/computed tomography be the first-line imaging investigation for restaging the laryngeal carcinoma patients?
Tarun Jain, Guman Singh, Sumit Goyal, Ajay Yadav, Dinesh Yadav, Nitin Khunteta, Hemant Malhotra
World Journal of Nuclear Medicine.2021; 20(02): 164. CrossRef
Modern Radiology in the Management of Head and Neck Cancer
G.J.C. Burkill, R.M. Evans, V.V. Raman, S.E.J. Connor
Clinical Oncology.2016; 28(7): 440. CrossRef
Synchronous Squamous Cell Carcinoma and Chronic Lymphocytic Leukemia of the Palate
Pablo Rosado, Soledad Fernández, Luis Junquera, Juan Carlos De Vicente
Journal of Craniofacial Surgery.2011; 22(1): 348. CrossRef

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Effects of REtinoic Acid and Radiation on the Growth of Cell Lines of Human Head and Neck Squamous Cell Carcinoma: Jae Hong Seo, Young Ah Yoo, In Keun Choi, Seok Jin Kim, Chul Won Choi, Byung Soo Kim, Chul Yong Kim, Sang Won Shin, Yeol Hong Kim, Myung Sun Choi, Joon Seok Kim; J Korean Cancer Assoc. 1998;30(4):772-780.

Abstract PDF: PURPOSE
Mammalian tumor cells differ in their response to ionizing radiation to a degree that some patients are readily curable with conventional doses of radiation, while others are rarely controlled. In experimental systems, it is possible to demonstrate differences between cell lines both in intrinsic radiosensitivity and in the apparent capacity to repair damage. Retinoic acid is a substance that has previously been reported to increase radiosensitivity, but at concentrations likely to have cytostatic effects or induce cellular differentiation. We chose several head and neck cancer cell lines to investigate radiation sensitivity and synergism in combination with retinoic acid. Material and Methods: Seventeen head and neck cancer cell lines (MDA886, P1, P13, A-431, PCI-50, UMSCC-10A, UMSCC-10B, UMSCC-11A, UMSCC-11B, UMSCC-17A, UMSCC-17B, UMSCC-19, UMSCC-22B, UMSCC-30, UMSCC-38, 1YA, 1YB) are irradiated with variable dose of radiation (1 Gy, 5 Gy, 9 Gy) for determination of radiosensitivity of each cell lines. The less radiosensitive cell lines are treated with retinoic acid for evaluation of the effects of retinoic acid on cellular X-ray sensitivity and recovery from X ray-induced potentially lethal damage.
RESULTS
Lowest growth inhibition rates are seen UMSCC-11A and 1YA cell lines in 1 Gy, so that we treated with retinoic acid such cell lines. We obtained the following RESULTS: 1) two cell lines appear not inhibitory effect on recovery from X-ray induced potentially lethal damage but growth inhibition synergism when irradiated with retinoic acid in 1 Gy of radiation dose. 2) two cell lines were little effect on radiosensitivity and inhibitory effect on recovery from X-ray damage in 0.5 Gy radiation dose.
CONCLUSION
We found that direct radiosensitizing effects of retinoic acid on 1 Gy of radiation dose may act synergistically for cell growth inhibition in vitro study(three cell lines: UMSCC-11A, 1YA, UMSCC-11B). Further in vitro and in vivo experiments are now necessary to evaluate retinoic acid as radiosensitizer for head and neck cancer radiation therapy.

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5-Fluorouracil , Cisplatin , and Pirarubicin Combination Chemotherapy for Advanced Gastric Cancer: Jae Hong Seo, In Keun Choi, Suk Jin Kim, Byung Soo Kim, Sang Won Shin, Yeul Hong Kim, Young Jae Mok, Jong Suk Kim, Jun Suk Kim; J Korean Cancer Assoc. 1998;30(3):475-481.

Abstract PDF: PURPOSE
Gastric cancer is the most common malignacy in Korea, However, standard systemic combination chemotherapy regimen has not been settled for advanced gastric cancer. 5-FU, Cisplatin, and Pirarubicin combination chemotherpay regimen has been tried to evaluate the response rate and toxicity in advanced gastric cancer patients.
MATERIALS AND METHODS
Elligibility included biopsy proven inoperable or relapsed adenocarcinoma of stomach with adequate bone marrow, hepatic, and renal functon. Thirty seven patients with histologically confinned locally advanced or metastatic gastric cancer were treated with cisplatin 15 mg/m2 IV day 1~5, pirarubicin 60 mg/m2 day 1, 5-fluorouracil 750 mg/m2 day 1~5 as a continuous intravenous infusion.
RESULTS
Twenty nine patients had measurable disease, 5 had received prior chemotherapy. Performance status was 0~1 in 24 and 2 in 13. There was 1 complete response and 13 partial response with an overall response rate of 48.3%(95% confidence interval 29.9~67.1%). The median survival is 7 months(95% confidence interval 5.4~8.6 months) and median response duration is 6 months. 19 patients experienced severe(WHO grade 3~4) leucopenia, 7 was thrombocytopenia, 13 was nausea and vomiting during chemotherapy. 11 patients experienced chemotherapy dose reduction or chemotherapy time delay due to severe hematologic or non-hematologic toxicities. There was no clinically recognizable cardiac toxicities.
CONCLUSION
We experienced 48.3% overall response rate, 7 months median survival, and 51.3% severe hematologic toxicities with 5-fluorouracil, pirarubicin and cisplatin combination chemotherapy regimen in advanced or metastatic gastric cancer patients.

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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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Multiple Primary malignant Tumors following Stomach Cancer Daignosis: In Keun Choi, Soo Sang Sohn, Joong Shin Kang; J Korean Cancer Assoc. 1995;27(5):829-836.

Abstract PDF: As progressively larger percentage of long-term survivors are being reported, the proportion of patients with subsequent primary lesions are increasing. This study is the clinical analysis of 17 cases of multiple primary malignant tumors confirmed fillowing the pathologic diagnosis of gastric cancer at the Department of Surgery, Keimyung University School of Medicine during the past 10 years from 1984 through 1994. These deta show that, when cancer first appears at a specific anetomic site, certain organs are more susceptible to second primary lesions than other sites. The ratio between male and female was 2:1 and mean age of incidence was 60 years. The ratio between synchronous and metachronous lesions was 1:2. The average time interval between first and second cancer was 3.0 years in metachronous cases. After the diagnosis of stomach cancer, the most frequently involved second organ was colorectum, others were liver, cervix, thyroid, and neck in decreasing order. Pathologic stage, tumor differentiation, tumor size, lymph node metastasis of the first lesions were unrelated to subsequent malignant tumor after stomach cancer diagnosis.

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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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