Cancer Research and Treatment

Original Articles

Phase II Study of Oxaliplatin, 5-fluorouracil, and Leucovorin in Relapsed or Metastatic Colorectal Cancer as Second Line Therapy: Duk-Joo Lee, Ho-Suk Oh, Jung-Hye Choi, Young-Yeul Lee, In-Soon Kim, Myung-Ju Ahn; Cancer Res Treat. 2006;38(4):201-205. Published online December 31, 2006; DOI: https://doi.org/10.4143/crt.2006.38.4.201

Abstract PDF PubReader ePub: Purpose
The purpose of the study was to assess the efficacy and safety of biweekly oxaliplatin in combination with leucovorin (LV)-modulated bolus plus infusion of 5-fluorouracil (5-FU) in patients with relapsed or metastatic colorectal cancer (CRC) as a second line therapy.
Materials and Methods
Between November 2002 and October 2005, 26 patients with histologically confirmed relapsed or metastatic CRC were enrolled. All patients were previously treated with irinotecan-based combination chemotherapy. The chemotherapy regimen consisted of oxaliplatin 85 mg/m² on day 1; LV 200 mg/m² on days 1 and 2; and 5-FU 400 mg/m² bolus IV with 600 mg/m² with a 22-hour infusion on days 1 and 2 every 2 weeks.
Results
The median age of the 26 patients was 50.5 years (range, 31~72). Their metastatic sites included: the liver (42.3%), peritoneum (26.9%), lung (23.1%) and ovary (7.7%). Twenty five patients were evaluated for their response. Four patients achieved partial responses and 15 patients had stable disease. The overall response rate was 16% (95% confidence interval; 1.7~30.3%). The median follow-up duration for the surviving patients was 7.4 months (range, 2.08~21.2). Median overall survival (OS) and 1-year OS rates were 16.7 months and 63.9%, respectively. The most common hematological toxicities were: NCI grade I/II leucopenia (49.3%), grade I/II neutropenia (41%) and grade I/II anemia (65.2%). The main non-hematological toxicities were: grade I/II peripheral neuropathy (16.1% and 21.5%, respectively) and nausea/vomiting (23.6%/18.5%). There was no life-threatening toxicity.
Conclusion
The oxaliplatin, 5-FU and LV combination chemotherapy, scheduled as a biweekly protocol, was effective and well tolerated in the treatment of relapsed or metastatic colorectal cancer patients as second line chemotherapy.

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Comparison of WHO and RECIST Criteria for Response in Metastatic Colorectal Carcinoma: Jung-Hye Choi, Myung-Ju Ahn, Hyan-Chul Rhim, Jin-Woo Kim, Gang-Hong Lee, Young-Yeul Lee, In-Soon Kim; Cancer Res Treat. 2005;37(5):290-293. Published online October 31, 2005; DOI: https://doi.org/10.4143/crt.2005.37.5.290

Purpose

This study compared the WHO criteria with the response evaluation criteria in solid tumors (RECIST) in the same patients with metastatic colorectal cancer in order to determine the significance of the RECIST. In addition, this study compared the estimations of medical oncologists with those of a radiologist.

Materials and Methods

Between 2002 and 2005, a total of 48 patients (male: female ratio, 29:19; median age, 58 years) with measurable lesions receiving chemotherapy for metastatic colorectal carcinoma were enrolled in this study. Two medical oncologists and one radiologist, who were blinded to the patients' condition, independently reviewed all the CT images. The results were compared using a kappa test.

Results

The kappa test for concordance between the WHO and RECIST criteria of the medical oncologists and the radiologist were 0.908 and 0.841, respectively. The level of concordance between the investigators using the WHO and RECIST were 0.722 and 0.753, respectively.

Conclusion

The RECIST criteria are comparable to the WHO criteria in evaluating the response of colorectal carcinoma, but have simple and reproducible guidelines. The use of RECIST is recommended for evaluating the treatment efficacy in clinical trials and practice.

Citations

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Thymidylate Synthase, Thymidine Phosphorylase, VEGF and p53 Protein Expression in Primary Colorectal Cancer for Predicting Response to 5-fluorouracil-based Chemotherapy: Myung-Ju Ahn, Jung-Hye Choi, Ho-Suk Oh, Young-Yeul Lee, In-Soon Kim, Il-Young Choi, Kang-Hong Lee, Kang-Won Song, Chan-Kum Park; Cancer Res Treat. 2005;37(4):216-222. Published online August 31, 2005; DOI: https://doi.org/10.4143/crt.2005.37.4.216

Abstract PDF PubReader ePub

Purpose

In the treatment of advanced metastatic colorectal cancer, several new agents, such as irinotecan and oxaliplatin, have been developed, which have improved both disease free and overall survivals. Among these agents, 5-fluorouracil (5-FU) still remains one of the most active agents, and the selection of patients who can benefit from 5-FU-based chemotherapy is still important, as those unlikely to benefit could be spared the harmful side effects. The expression levels of thymidylate synthase (TS), thymidine phosphorylase (TP) and p53 have been known to be associated with the clinical response to 5-FU-based therapy as well as the prognosis, and that of vascular endothelial growth factor (VEGF) is associated with poor survival.

Materials and Methods

The relationship between the expressions of TS, TP, VEGF and p53 in primary tumors, using immunohistochemistry, and the response of 45 metastatic colorectal cancer patients (M:F=25:20, median age 59 yrs) to 5-FU-based chemotherapy were evaluated.

Results

Thirty-seven patients were treated with 5-FU/LV/irinotecan (FOLFIRI) and 8 with 5-FU/LV/oxaplatin (FOLFOX). The overall response rate was 28.9% (13/45). When immunohistochemically analyzed with monoclonal antibodies against TS, TP, VEGF and p53, 55.6% of the patients (25/45) were positive for TS, 48.9% (22/45) for TP, 82.2% (37/45) for VEGF, and 80% (36/45) for p53. There was a significant difference in the intensity of TS expression between the clinical responders and non-responders (p=0.036). In terms of the staining pattern of TS expression, diffuse staining was correlated with a poor response (p=0.012) and poor survival (p=0.045). However, there was no correlation between the expressions of TP, VEGF or P53 and the response to chemotherapy.

Conclusion

These results suggest that the expression of TS in primary colorectal cancer might be an important prognostic factor for chemotherapy response and survival, and might be a useful therapeutic marker for the response of chemotherapy.

Citations

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Epigenetic Approaches to Overcome Fluoropyrimidines Resistance in Solid Tumors
Laura Grumetti, Rita Lombardi, Federica Iannelli, Biagio Pucci, Antonio Avallone, Elena Di Gennaro, Alfredo Budillon
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Wilson Roberto Batista, Gianni Santos, Flávia Maria Ribeiro Vital, Delcio Matos
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Thymidine phosphorylase expression and prognosis in colorectal cancer treated with 5‑fluorouracil‑based chemotherapy: A meta‑analysis
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Molecular and Clinical Oncology.2017;[Epub] CrossRef
Does anti-p53 antibody status predict for clinical outcomes in metastatic colorectal cancer patients treated with fluoropyrimidine, oxaliplatin, plus bevacizumab as first-line chemotherapy?
Hiroki Osumi, Eiji Shinozaki, Mitsukuni Suenaga, Yosuke Kumekawa, Mariko Ogura, Masato Ozaka, Satoshi Matsusaka, Keisho Chin, Noriko Yamamoto, Nobuyuki Mizunuma
BMC Cancer.2015;[Epub] CrossRef
Comparison of thymidine phosphorylase expression and prognostic factors in gallbladder and bile duct cancer
Hye Sung Won, Myung Ah Lee, Eun-Seon Chung, Dong-Goo Kim, Young Kyoung You, Tae Ho Hong, In-Seok Lee
BMC Cancer.2010;[Epub] CrossRef

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Phase II Study of Irinotecan, 5-Fluorouracil, and Leucovorin in Relapsed or Metastatic Colorectal Cancer as First-line Therapy: Young-Woong Won, Young-Hyo Lim, Ho-Yong Park, Ho-Suk Oh, Jung-Hye Choi, Young-Yeul Lee, In-Soon Kim, Il-Young Choi, Myung-Ju Ahn; Cancer Res Treat. 2004;36(4):235-239. Published online August 31, 2004; DOI: https://doi.org/10.4143/crt.2004.36.4.235

Abstract PDF PubReader ePub

Background

The purpose of this study was to assess the efficacy and toxicity of biweekly irinotecan plus 5-fluorouracil (FU) and leucovorin (LV) in patients with relapsed or metastatic colorectal cancer.

Materials and Methods

Between March 2002 and May 2004, 24 patients with histologically confirmed relapsed or metastatic colorectal cancer were enrolled in this study. One chemotherapy cycle consisted of irinotecan 180 mg/m² on days 1 and 15; 5-FU 400 mg/m² bolus IV with 600 mg/m² by a 22 hour intravenous infusion on days 1, 2, 15 and 16; and leucovorin 20 mg/m² on days 1, 2, 15 and 16, every 4 weeks.

Results

The median age of the 24 was 57.5 years (range, 38~69). Their metastatic sites included: the liver (62.5%), lung (20.8%), peritoneum (16.7%), lymph node (12.5%), ovary (8.3%) and pelvis/vagina (8.3%). Twenty-two patients were evaluable for a response. Six and 7 patients achieved partial responses and stable diseases, respectively. The overall response rate was 27.3% (95% Confidence interval; 10.3~44.5%). The median follow-up duration for surviving patients was 14.7 months (range, 1.7~26.5). Median overall survival (OS) and 1-year OS rates were 19 months and 86.3%, respectively. Median response duration and median progression free survival were 7.47 and 5.57 months, respectively. A total of 83 cycles (median 4 cycles) were administered. The main non-hematologic toxicities were nausea/vomiting (44.5%/18.1%) and diarrhea (8.4%). The most common hematologic toxicity was NCI grade I/II anemia (31.3%) and grade I/II neutropenia was 10.8%. There was no life-threatening toxicity.

Conclusion

The results suggested that irinotecan, 5-FU and leucovorin combination chemotherapy in a biweekly schedule is a practical and tolerable treatment option in patients with advanced colorectal cancer.

Citations

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A Phase I Study of UGT1A1 *28/*6 Genotype-Directed Dosing of Irinotecan (CPT-11) in Korean Patients with Metastatic Colorectal Cancer Receiving FOLFIRI
Kyu-Pyo Kim, Yong Sang Hong, Jae-Lyun Lee, Kyun Seop Bae, Ho-Sook Kim, Jae-Gook Shin, Jung Shin Lee, Tae Won Kim
Oncology.2015; 88(3): 164. CrossRef
Effect of an Irinotencan, 5-Fluorouracil, and Leucovorin Combination Chemotherapy (FOLFIRI) in Metastatic Colorectal Cancer
Seung Hyun Lee, Byung Kwon Ahn, Sung Uhn Baek
Journal of the Korean Society of Coloproctology.2007; 23(5): 333. CrossRef
A Phase II Study of Irinotecan, 5-Fluorouracil and Leucovorin for Treatment in Patients with Previously Untreated Advanced Colorectal Cancer
Sang-Byung Bae, Nam-Su Lee, Han-Jo Kim, Kyoung-Ha Kim, Hyun-Jung Kim, Chan-Kyu Kim, Kyu-Taeg Lee, Sung-Kyu Park, Jong-Ho Won, Dae-Sik Hong, Hee-Sook Park
Cancer Research and Treatment.2006; 38(2): 72. CrossRef
Irinotecan, Continuous 5-Fluorouracil, and Low dose of Leucovorin (modified FOLFIRI) as First Line of Therapy in Recurrent or Metastatic Colorectal Cancer
Myung-Ah Lee, Jae-Ho Byun, Byoung-Young Shim, In-Sook Woo, Jin-Hyung Kang, Young Seon Hong, Kyung Shik Lee, Myung Gyu Choi, Suk Kyun Chang, Seong Taek Oh, Sung Il Choi, Doo Suk Lee
The Korean Journal of Internal Medicine.2005; 20(3): 205. CrossRef
Responsiveness of CPT-11 in Respect to hMLH1 and hMSH2 Protein Expression in the Primary Colorectal Cancer
In Ja Park, Hee Cheol Kim, Chang Sik Yu, Heung Moon Chang, Jea Hwan Lee, Jong Hoon Kim, Tae Won Kim, Jung Sun Kim, Jin Cheon Kim
Cancer Research and Treatment.2004; 36(6): 360. CrossRef

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Combination Chemotherapy of Heptaplatin, Paclitaxel and 5-Fluorouracil in Patients with Advanced Gastric Cancer: a Pilot Study: Myung-Ju Ahn, Ho-Suck Oh, Jung-Hye Choi, Young-Yeul Lee, In-Soon Kim, Il-Young Choi, Oh Young Lee, Ho-Soon Choi, Sung-Joon Kwon; Cancer Res Treat. 2004;36(3):182-186. Published online June 30, 2004; DOI: https://doi.org/10.4143/crt.2004.36.3.182

Abstract PDF PubReader ePub

Purpose

To evaluate the efficacy and toxicity of heptaplatin, paclitaxel, and 5-fluorouracil combination chemotherapy in patients with advanced gastric cancer.

Materials and Methods

Between July 2002 and September 2003, nineteen patients were enrolled in this study. Paclitaxel 135 mg/m² iv on day 1, heptaplatin 400 mg/m² iv on day 2 and 5-fluorouracil 800 mg/m² on day 2~4 were administered and the regimen was repeated every 3 weeks.

Results

The median age of the patients was 60 years (range: 32~74) and the most common sites of metastasis were liver and lymph nodes. In the 16 evaluated patients, the overall response rate was 43.8%, but this was without any complete response. The median time to disease progression was 3.93 months (range: 0.26~8.1) and the median response duration for the 7 responding patients was 3.83 months (range: 1.48~6.07). The median overall survival for 19 patients was 7.01 months (range: 0.26~17.44). A median of 3 cycles (range: 1~7) and a total of 65 cycles were administered and evaluated for toxicity. The most common hematologic toxicities were NCI grade I/II anemia (47.7%), neutropenia (9.2%) and thrombocytopenia (6.2%). The most common non-hematologic toxicities more than grade II were nausea/vomiting (30.8%/9.2%). One elderly patient with ECOG 2 had a life-threatening complication of pneumonia.

Conclusion

The combination of heptaplatin, paclitaxel, and 5-fluorouracil showed significant activity and favorable toxicity profiles in patients with advanced gastric cancer. However, one elderly patient who had poor performance experienced a life-threatening toxicity/complication. Our results suggest that the efficacy of this combination chemotherapy can be maximized when administered to the patients with good performance status. Further studies with large numbers of patients and long-term follow-up study will be needed.

Citations

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Application of Approved Cisplatin Derivatives in Combination Therapy against Different Cancer Diseases
Dobrina Tsvetkova, Stefka Ivanova
Molecules.2022; 27(8): 2466. CrossRef
Synthesis of novel heptaplatin derivatives and evaluation of their ability to inhibit proliferation of cancer cell lines
W. Xu, D. C. Wang
Russian Journal of General Chemistry.2016; 86(4): 939. CrossRef

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Radiofrequency Ablation for Metastatic Hepatic Tumor in Colorectal Carcinoma: Jung-Hye Choi, Myung-Ju Ahn, Hyunchul Rhim, Heung Woo Lee, Ho-Suk Oh, Young-Yeul Lee, Il-Young Choi, In-Soon Kim; Cancer Res Treat. 2004;36(2):128-131. Published online April 30, 2004; DOI: https://doi.org/10.4143/crt.2004.36.2.128

Abstract PDF PubReader ePub

Purpose

The purpose of this study was to assess the efficacy and safety of radiofrequency ablation (RFA) to treat hepatic metastasis in patients with colorectal carcinoma.

Materials and Methods

Between May 1999 and July 2002, a total of 45 tumors in 24 patients with colorectal cancer were treated with RFA. Thirteen patients received systemic chemotherapy after the RFA procedure. The ablation was performed percutaneously under ultrasound guidance using cool-tip or expandable electrodes and an RF generator. The medical records as well as the CT scan results taken every 3 months were retrospectively reviewed.

Results

The median follow-up duration of the surviving patients was 11.7 months (4.6~32.2 months). Complete tumor necrosis was achieved in 17 patients (70.8%) on an immediate (<24 hrs) CT scan. The median survival was 17.1 months. The 1- and 2-year survival rates were 80.5 and 25.8%, respectively. In a univariate analysis, complete necrosis, tumor size and post-RFA chemotherapy were significant factors for survival. Nineteen of the 24 patients developed a recurrence or progressed (79.2%). The median progression free survival was 5.5 months. There were no treatment related deaths or serious adverse effects, with the exception of one case of respiratory failure.

Conclusion

These results suggest that RFA is a well-tolerated and effective method to treat hepatic metastasis in colorectal carcinomas.

Citations

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Susann-Cathrin Olthof, Daniel Wessling, Moritz T. Winkelmann, Hansjörg Rempp, Konstantin Nikolaou, Rüdiger Hoffmann, Stephan Clasen
Insights into Imaging.2022;[Epub] CrossRef
Prognostic factors after ultrasound‐guided percutaneous ablation of colorectal liver metastases: A systematic review
Jeanett Klubien, Andreas P. Kohl, Christian P. Nolsøe, Jacob Rosenberg, Hans‐Christian Pommergaard
Australasian Journal of Ultrasound in Medicine.2018; 21(2): 87. CrossRef
Impact of timing and cycles of systemic chemotherapy on survival outcome of colorectal liver metastases patients treated by percutaneous microwave ablation
Kai Zhang, Jie Yu, Fubo Zhou, Xiaoling Yu, Xin Li, Jianbin Wang, Zhiyu Han, Zhigang Cheng, Ping Liang
International Journal of Hyperthermia.2016; 32(5): 531. CrossRef
Efficacy and safety of thermal ablation in patients with liver metastases
Yingjun Liu, Shengping Li, Xiangbin Wan, Yi Li, Binkui Li, Yaqi Zhang, Yunfei Yuan, Yun Zheng
European Journal of Gastroenterology & Hepatology.2013; 25(4): 442. CrossRef
CT- versus coregistered FDG-PET/CT-based radiation therapy plans for conformal radiotherapy in colorectal liver metastases: a dosimetric comparison
Cem Parlak, Erkan Topkan, Serhat Sonmez, Cem Onal, Mehmet Reyhan
Japanese Journal of Radiology.2012; 30(8): 628. CrossRef

8,076 View
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