Cancer Research and Treatment

Original Article

Gastrointestinal cancer

A Phase II Study of Preoperative Chemoradiotherapy with Capecitabine Plus Simvastatin in Patients with Locally Advanced Rectal Cancer: Hyunji Jo, Seung Tae Kim, Jeeyun Lee, Se Hoon Park, Joon Oh Park, Young Suk Park, Ho Yeong Lim, Jeong Il Yu, Hee Chul Park, Doo Ho Choi, Yoonah Park, Yong Beom Cho, Jung Wook Huh, Seong Hyeon Yun, Hee Cheol Kim, Woo Yong Lee, Won Ki Kang; Cancer Res Treat. 2023;55(1):189-195. Published online June 8, 2022; DOI: https://doi.org/10.4143/crt.2021.1527

Purpose
The purpose of this phase II trial was to evaluate whether the addition of simvastatin, a synthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, to preoperative chemoradiotherapy (CRT) with capecitabine confers a clinical benefit to patients with locally advanced rectal cancer (LARC).
Materials and Methods
Patients with LARC (defined by clinical stage T3/4 and/or lymph node positivity) received preoperative radiation (45-50.4 Gy in 25-28 daily fractions) with concomitant capecitabine (825 mg/m2 twice per day) and simvastatin (80 mg, daily). Curative surgery was planned 4-8 weeks after completion of the CRT regimen. The primary endpoint was pathologic complete response (pCR). The secondary endpoints included sphincter-sparing surgery, R0 resection, disease-free survival, overall survival, the pattern of failure, and toxicity.
Results
Between October 2014 and July 2017, 61 patients were enrolled; 53 patients completed CRT regimen and underwent total mesorectal excision. The pCR rate was 18.9% (n=10) by per-protocol analysis. Sphincter-sparing surgery was performed in 51 patients (96.2%). R0 resection was achieved in 51 patients (96.2%). One patient experienced grade 3 liver enzyme elevation. No patient experienced additional toxicity caused by simvastatin.
Conclusion
The combination of 80 mg simvastatin with CRT and capecitabine did not improve pCR in patients with LARC, although it did not increase toxicity.

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Effects of Hyperlipidemia on Osseointegration of Dental Implants and Its Strategies
Haiyang Sun, Shuhuai Meng, Junyu Chen, Qianbing Wan
Journal of Functional Biomaterials.2023; 14(4): 194. CrossRef

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Review Article

Systemic Treatment of Advanced Gastroenteropancreatic Neuroendocrine Tumors in Korea: Literature Review and Expert Opinion: Changhoon Yoo, Chung Ryul Oh, Seung-Tae Kim, Woo Kyun Bae, Hye-Jin Choi, Do-Youn Oh, Myung-Ah Lee, Baek-Yeol Ryoo; Cancer Res Treat. 2021;53(2):291-300. Published online December 29, 2020; DOI: https://doi.org/10.4143/crt.2020.1233

Abstract PDF PubReader ePub

Neuroendocrine tumors (NETs) are a group of malignancies arising from neuroendocrine cells and frequently originate in the gastrointestinal tract and pancreas. Although curative resection is the main treatment for localized disease, systemic therapy is needed for relapsed or metastatic/unresectable gastroenteropancreatic NETs (GEP-NETs). Although there are several NET treatment guidelines from various countries, the geographical discrepancies between patient clinical characteristics, the regulatory approval status for therapeutic agents, and medical practices necessitate specific guidelines for Korean patients. We here provide a consensus review of the diagnosis, staging and systemic treatment of Korean GEP-NET patients. Systemic therapy options and the current Korean expert consensus on these treatments, including somatostatin analogs, targeted therapies such as everolimus and sunitinib, peptide receptor radionuclide treatments, and cytotoxic chemotherapies are addressed.

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Efficacy and Safety of Lu-177 DOTATATE Peptide Receptor Radionuclide Therapy in Patients with Unresectable or Metastatic Neuroendocrine Tumors in Korea
Yeokyeong Shin, Bo Hyun Moon, Baek-Yeol Ryoo, Heung-Moon Chang, Kyu-pyo Kim, Yong Sang Hong, Tae Won Kim, Jin-Sook Ryu, Yong-il Kim, Changhoon Yoo
Targeted Oncology.2024; 19(1): 41. CrossRef
Effectiveness and Safety of Retreatment with177Lu-DOTATATE in Patients with Progressive Neuroendocrine Tumors: A Retrospective Real-World Study in the United States
Ebrahim S. Delpassand, Soheil M. Yazdi, Shashank Ghantoji, Antonio Nakasato, Corinne Strickland, Rodolfo Nunez, Afshin Shafie, Susan Cork, Clare Byrne, Jackson Tang, Jeetvan Patel
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Yuan Zhou, Maoen Pan, Ronggui Lin, Heguang Huang
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Prognostic value of interim [68Ga]Ga-DOTA-TOC PET/CT in patients with neuroendocrine tumour who underwent peptide receptor radionuclide therapy
Eonwoo Shin, Yong-il Kim, Changhoon Yoo, Yeokyeong Shin, Baek-Yeol Ryoo, Dong Yun Lee, Jin-Sook Ryu
European Radiology.2024;[Epub] CrossRef
Consideration of quality of life in the treatment decision-making for patients with advanced gastroenteropancreatic neuroendocrine tumors
Boris G. Naraev, Josh Mailman, Thorvardur R. Halfdanarson, Heloisa P. Soares, Erik S. Mittra, Julie Hallet
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Capecitabine plus temozolomide in patients with grade 3 unresectable or metastatic gastroenteropancreatic neuroendocrine neoplasms with Ki-67 index <55%: single-arm phase II study
H. Jeong, J. Shin, J.H. Jeong, K.-p. Kim, S.-M. Hong, Y.-i. Kim, J.-S. Ryu, B.-Y. Ryoo, C. Yoo
ESMO Open.2021; 6(3): 100119. CrossRef

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Original Articles

Gastrointestinal Cancer

Polymorphisms in TYMS for Prediction of Capecitabine-Induced Hand-Foot Syndrome in Chinese Patients with Colorectal Cancer: Si-Qi Dong, Tong-Min Wang, Jiang-Bo Zhang, Yong-Qiao He, Wen-Qiong Xue, Zi-Yi Wu, Da-Wei Yang, Lian-Jing Cao, Jing-Wen Huang, Xi-Zhao Li, Pei-Fen Zhang, Xiao-Hui Zheng, Wei-Hua Jia; Cancer Res Treat. 2021;53(3):724-732. Published online December 2, 2020; DOI: https://doi.org/10.4143/crt.2020.457

Abstract PDF Supplementary Material PubReader ePub

Purpose
Capecitabine is an extensively used oral prodrug of 5-fluorouracil in treatment of colon cancer and is known to cause hand-foot syndrome (HFS). As the target enzyme for capecitabine, thymidylate synthase (TYMS) plays a key role for 5-fluorouracil metabolism and has been associated with some side effects caused by capecitabine. The aim of our study is to identify the possible genetic predictors of capecitabine-induced HFS (CAP-HFS) in Chinese colorectal cancer patients.
Materials and Methods
Whole exons of TYMS were sequenced for 288 extreme phenotype HFS patients, including 144 severe or early-onset (first 2 cycles) moderate HFS extreme cases and 144 extreme controls with no reported HFS. The associations between polymorphisms and CAP-HFS were analyzed using logistic regression under an additive model.
Results
We identified a novel risk mutation (c.1A>G, chr18:657743), was associated with severe HFS in an extreme case who was affected during the first cycle of treatment. Moreover, we identified three new variants, rs3786362, rs699517, rs2790, and two previously reported variants, 5’VNTR 2R/3R and 3′-untranslated region 6-bp ins-del, which were significantly associated with CAP-HFS (p < 0.05). In silico analysis revealed that the effect of these polymorphisms in the TYMS region on the development of HFS might not be restricted solely to the regulation of TYMS expression, but also the TYMS catalytic activity through the indirect effect on ENOSF1 expression.
Conclusion
This study identified new polymorphisms in TYMS gene significantly associated with CAP-HFS, which may serve as useful genetic predictors for CAP-HFS and help to elucidate the underlying mechanism of HFS.

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Fuhua Yu, Lei Shi, Qianru Wang, Xiaohui Xing, Zhongchen Li, Lei Hou, Zhengshan Zhou, Zengguang Wang, Yilei Xiao
Biochemical Genetics.2024; 62(1): 468. CrossRef
MTHFR 677 C>T- and 1298 A>C-related adverse effects in 5-fluorouracil-based chemotherapy in the Asian population: a systematic review and meta-analysis
Yu Bai, Dan Jiang, Yong-qing Wen, Wen-juan Wang, Zai-wei Song
Discover Medicine.2024;[Epub] CrossRef
Influence of Single-Nucleotide Polymorphisms on Clinical Outcomes of Capecitabine-Based Chemotherapy in Colorectal Cancer Patients: A Systematic Review
Yasmin Cura, Cristina Pérez-Ramírez, Almudena Sánchez-Martín, Cristina Membrive-Jimenez, María Isabel Valverde-Merino, Encarnación González-Flores, Alberto Jiménez Morales
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Capecitabine

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Alessia Bignucolo, Lucia Scarabel, Giuseppe Toffoli, Erika Cecchin, Elena De Mattia
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DNA damage repair-related gene signature predicts prognosis and indicates immune cell infiltration landscape in skin cutaneous melanoma
Liping Liang, Shijie Mai, Genghui Mai, Ye Chen, Le Liu
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Journal of Personalized Medicine.2021; 11(8): 792. CrossRef

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Randomized Open Label Phase III Trial of Irinotecan Plus Capecitabine versus Capecitabine Monotherapy in Patients with Metastatic Breast Cancer Previously Treated with Anthracycline and Taxane: PROCEED Trial (KCSG BR 11-01): In Hae Park, Seock-Ah Im, Kyung Hae Jung, Joo Hyuk Sohn, Yeon Hee Park, Keun Seok Lee, Sung Hoon Sim, Kyong-Hwa Park, Jee Hyun Kim, Byung Ho Nam, Hee-Jun Kim, Tae-Yong Kim, Kyung-Hun Lee, Sung-Bae Kim, Jin-Hee Ahn, Suee Lee, Jungsil Ro; Cancer Res Treat. 2019;51(1):43-52. Published online February 14, 2018; DOI: https://doi.org/10.4143/crt.2017.562

Abstract PDF PubReader ePub

Purpose
We investigated whether irinotecan plus capecitabine improved progression-free survival (PFS) compared with capecitabine alone in patients with human epidermal growth factor 2 (HER2) negative and anthracycline and taxane pretreated metastatic breast cancer (MBC).
Materials and Methods
A total of 221 patients were randomly assigned to irinotecan (80 mg/m2, days 1 and 8) and capecitabine (1,000 mg/m2 twice a day, days 1-14) or capecitabine alone (1,250 mg/m2 twice a day, days 1-14) every 3 weeks. The primary endpoint was PFS.
Results
There was no significant difference in PFS between the combination and monotherapy arm (median, 6.4 months vs. 4.7 months; hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.63 to 1.11; p=0.84). In patients with triple-negative breast cancer (TNBC, n=90), the combination significantly improved PFS (median, 4.7 months vs. 2.5 months; HR, 0.58; 95% CI, 0.37 to 0.91; p=0.02). Objective response rate was numerically higher in the combination arm, though it failed to reach statistical significance (44.4% vs. 33.3%, p=0.30). Overall survival did not differ between arms (median, 20.4 months vs. 24.0 months; p=0.63). While grade 3 or 4 neutropenia was more common in the combination arm (39.6% vs 9.0%), hand-foot syndrome was more often observed in capecitabine arm. Quality of life measurements in global health status was similar. However, patients in the combination arm showed significantly worse symptom scales especially in nausea/vomiting and diarrhea.
Conclusion
Irinotecan plus capecitabine did not prove clinically superior to single-agent capecitabine in anthracycline- and taxane-pretreated HER2 negative MBC patients. Toxicity profiles of the two groups differed but were manageable. The role of added irinotecan in patients with TNBC remains to be elucidated.

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450 Download
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Phase I Study of Axitinib in Combination with Cisplatin and Capecitabine in Patients with Previously Untreated Advanced Gastric Cancer: Do-Youn Oh, Toshihiko Doi, Kuniaki Shirao, Keun-Wook Lee, Sook Ryun Park, Ying Chen, Liqiang Yang, Olga Valota, Yung-Jue Bang; Cancer Res Treat. 2015;47(4):687-696. Published online February 12, 2015; DOI: https://doi.org/10.4143/crt.2014.225

Abstract PDF PubReader ePub

Purpose
This phase I trial evaluated the question of whether the standard starting dose of axitinib could be administered in combination with therapeutic doses of cisplatin/capecitabine in patients with previously untreated advanced gastric cancer, and assessed overall safety, pharmacokinetics, and preliminary antitumor activity of this combination.
Materials and Methods
Patients in dose level (DL) 1 received axitinib 5 mg twice a day (days 1 to 21) with cisplatin 80 mg/m2 (day 1) and capecitabine 1,000 mg/m2 twice a day (days 1 to 14) in 21-day cycles. Maximum tolerated dose (MTD) was the highest dose at which ≤ 30% of the first 12 patients experienced a dose-limiting toxicity (DLT) during cycle 1. Ten additional patients were enrolled and treated at the MTD in order to obtain additional safety and pharmacokinetic data.
Results
Three DLTs occurred during cycle 1 in three (25%) of the first 12 patients: ruptured abdominal aortic aneurysm, acute renal failure, and > 5 consecutive days of missed axitinib due to thrombocytopenia. DL1 was established as the MTD, since higher DL cohorts were not planned. Common grade 3/4 non-hematologic adverse events in 22 patients treated at DL1 included hypertension (36.4%) and decreased appetite and stomatitis (18.2% each). Cisplatin/capecitabine slightly increased axitinib exposure; axitinib decreased capecitabine and 5-fluorouracil exposure. Eight patients (36.4%) each had partial response or stable disease. Median response duration was 9.1 months; median progression-free survival was 3.8 months.
Conclusion
In patients with advanced gastric cancer, standard doses of axitinib plus therapeutic doses of cisplatin and capecitabine could be administered in combination. Adverse events were manageable.

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A Randomized Phase II Trial of Capecitabine Plus Vinorelbine Followed by Docetaxel Versus Adriamycin Plus Cyclophosphamide Followed by Docetaxel as Neoadjuvant Chemotherapy for Breast Cancer: Changhoon Yoo, Sung-Bae Kim, Jin-Hee Ahn, Jeong Eun Kim, Kyung Hae Jung, Gyung-Yub Gong, Byung-Ho Son, Sei-Hyun Ahn, Seung Do Ahn, Hak-Hee Kim, Hee Jung Shin, Woo Kun Kim; Cancer Res Treat. 2015;47(3):406-415. Published online November 27, 2014; DOI: https://doi.org/10.4143/crt.2014.073

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Purpose
Given the promising activity of capecitabine and vinorelbine in metastatic breast cancer, this randomized phase II trial evaluated the efficacy and safety of this combination as neoadjuvant chemotherapy in breast cancer. Materials and Methods Patients with operable breast cancer (n=75) were randomly assigned to receive either four cycles of adriamycin 60 mg/m2 plus cyclophosphamide 600 mg/m2 every 3 weeks followed by four cycles of docetaxel 75 mg/m2 every 3 weeks (AC-D) or four cycles of capecitabine 2,000 mg/m2 (day 1-14) plus vinorelbine 25 mg/m2 (days 1 and 8) every 3 weeks followed by four cycles of docetaxel 75 mg/m2 (CV-D). The primary endpoint was pathologic complete response (pCR) in the primary breast (ypT0/is). Results Most patients (84%) had locally advanced (n=41) or inflammatory breast cancer (n=22). pCR rates in the primary breast were 15% (95% confidence interval [CI], 7% to 30%) and 11% (95% CI, 4% to 26%) in the AC-D and CV-D groups, respectively. The overall response rates and 5-year progression-free survival rates in the AC-D and CV-D groups were 62% and 64%, and 51.3% (95% CI, 34.6% to 68.0%) and 30.2% (95% CI, 13.3% to 47.1%), respectively. Although both regimens were well tolerated, CV-D showed less frequent grade 3-4 neutropenia and vomiting than AC-D, whereas manageable diarrhea and hand-foot syndrome were more common in the CV-D group. Conclusion CV-D is a feasible and active non-anthracycline–based neoadjuvant chemotherapy regimen for breast cancer.

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rApoptin induces apoptosis in human breast cancer cells via phosphorylation of Nur77 and Akt
Zhenhuan Hou, Jun Mao, Ying Lu, Lianhong Li
Biochemical and Biophysical Research Communications.2018; 498(1): 221. CrossRef
Neoadjuvant systemic therapy in breast cancer: Challenges and uncertainties
Mick Van de Wiel, Yanina Dockx, Tim Van den Wyngaert, Sigrid Stroobants, Wiebren A.A. Tjalma, Manon T. Huizing
European Journal of Obstetrics & Gynecology and Reproductive Biology.2017; 210: 144. CrossRef
Human serum albumin-mediated apoptin delivery suppresses breast cancer cell growth in vitro and in vivo
Fang Wu, Yizhi Liu, Jian Li, Lei Hou, Fuxi Lei, Shangke Huang, Lu Feng, Xinhan Zhao
Oncology Letters.2017; 13(2): 579. CrossRef
Capecitabine in Combination with Standard (Neo)Adjuvant Regimens in Early Breast Cancer: Survival Outcome from a Meta-Analysis of Randomized Controlled Trials
Ze-Chun Zhang, Qi-Ni Xu, Sui-Ling Lin, Xu-Yuan Li, Hemant Kumar Bid
PLOS ONE.2016; 11(10): e0164663. CrossRef

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Comparison of the Efficacy between Gemcitabine-Cisplatin and Capecitabine-Cisplatin Combination Chemotherapy for Advanced Biliary Tract Cancer: Jieun Lee, Tae Ho Hong, In Seok Lee, Young Kyoung You, Myung Ah Lee; Cancer Res Treat. 2015;47(2):259-265. Published online September 12, 2014; DOI: https://doi.org/10.4143/crt.2013.230

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Purpose
Gemcitabine-cisplatin combination chemotherapy has been regarded as standard regimen for advanced or metastatic biliary tract cancer (BTC), based on the ABC-02 trial. To date, however, no studies have compared the efficacies of gemcitabine-platinum and fluoropyrimidine- platinum combination chemotherapy, even though fluoropyrimidine has been widely used as a backbone agent for gastrointestinal cancer. This study compared the efficacy and toxicities of gemcitabine-cisplatin (GP) and capecitabine-cisplatin (XP) combination chemotherapy for treatment of advanced BTC. Materials and Methods We examined 49 patients treated with GP and 44 patients treated with XP from October 2009 to July 2012. All patients had unresectable BTC. The GP regimen comprised gemcitabine (1,000 mg/m2, intravenously [IV], days 1 and 8) and cisplatin (75 mg/m2, IV, day 1). The XP regimen comprised capecitabine (1,250 mg/m2 twice a day, peroral, days 1-14) and cisplatin (60 mg/m2, IV, day 1, every three weeks). We analyzed the response rate (RR), time to progression (TTP), overall survival (OS), and toxicity. Results The RRs were 27.3% and 6.1% in the XP and GP arms, respectively. XP resulted in longer TTP (5.2 months vs. 3.6 months, p=0.016), but OS was not statistically different (10.7 months vs. 8.6 months, p=0.365). Both regimens resulted in grade 3-4 hematologic toxicities, but febrile neutropenia was not noted. Grade 3-4 asthenia, stomatitis, and hand-foot syndrome occurred more frequently in the XP arm. Conclusion XP resulted in a superior TTP and RR compared to GP for treatment of advanced BTC, with comparable toxicity. Conduct of prospective large, randomized trials to evaluate the possibility of XP as another standard therapy is warranted.

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Pristine B 40 fullerene as a potential gemcitabine drug carrier for anti-lung cancer properties: a DFT and QTAIM study
Abisha Nancy Sukumar, Parimala Devi Duraisamy, Prince Makarios Paul. S, Praveena Gopalan, Abiram Angamuthu
Journal of Biomolecular Structure and Dynamics.2024; : 1. CrossRef
A Practical Guide for the Systemic Treatment of Biliary Tract Cancer in Canada
Ravi Ramjeesingh, Prosanto Chaudhury, Vincent C. Tam, David Roberge, Howard J. Lim, Jennifer J. Knox, Jamil Asselah, Sarah Doucette, Nirlep Chhiber, Rachel Goodwin
Current Oncology.2023; 30(8): 7132. CrossRef
A Systematised Literature Review of Real-World Treatment Patterns and Outcomes in Unresectable Advanced or Metastatic Biliary Tract Cancer
Vivian Peirce, Michael Paskow, Lei Qin, Ruby Dadzie, Maria Rapoport, Samantha Prince, Sukhvinder Johal
Targeted Oncology.2023; 18(6): 837. CrossRef
Chemotherapy for Biliary Tract Cancer in 2021
Takashi Sasaki, Tsuyoshi Takeda, Takeshi Okamoto, Masato Ozaka, Naoki Sasahira
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Comparison between Fluoropyrimidine-Cisplatin and Gemcitabine-Cisplatin as First-Line Chemotherapy for Advanced Biliary Tract Cancer: A Meta-Analysis
Ting Zheng, Jianjiang Jin, Li Zhou, Yuefeng Zhang
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Yan Li, Yaoyao Zhou, Yonglan Hong, Meizhi He, Shuyi Wei, Chen Yang, Dayong Zheng, Feiye Liu
Frontiers in Oncology.2019;[Epub] CrossRef
Gemcitabine-based chemotherapy for advanced biliary tract carcinomas
Omar Abdel-Rahman, Zeinab Elsayed, Hesham Elhalawani
Cochrane Database of Systematic Reviews.2018;[Epub] CrossRef
A randomised phase II study of second-line XELIRI regimen versus irinotecan monotherapy in advanced biliary tract cancer patients progressed on gemcitabine and cisplatin
Yi Zheng, Xiaoxuan Tu, Peng Zhao, Weiqin Jiang, Lulu Liu, Zhou Tong, Hangyu Zhang, Cong Yan, Weijia Fang, Weilin Wang
British Journal of Cancer.2018; 119(3): 291. CrossRef
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Dae-Won Lee, Seock-Ah Im, Yu Jung Kim, Yaewon Yang, Jiyoung Rhee, Im Il Na, Kyung-Hun Lee, Tae-Yong Kim, Sae-Won Han, In Sil Choi, Do-Youn Oh, Jee Hyun Kim, Tae-You Kim, Yung-Jue Bang
Cancer Research and Treatment.2017; 49(3): 807. CrossRef
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Gemcitabine Combined with Capecitabine Compared to Gemcitabine with or without Erlotinib as First-Line Chemotherapy in Patients with Advanced Pancreatic Cancer: Jae Yun Lim, Jang Ho Cho, Se Joon Lee, Dong Ki Lee, Dong Sup Yoon, Jae Yong Cho; Cancer Res Treat. 2015;47(2):266-273. Published online August 29, 2014; DOI: https://doi.org/10.4143/crt.2013.158

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Purpose
The purpose of this study is to retrospectively compare the efficacy and tolerability between three regimens for first-line chemotherapy—gemcitabine plus capecitabine (GEM-X), gemcitabine plus erlotinib (GEM-T), and gemcitabine monotherapy (GEM)—in patients with advanced pancreatic cancer. Materials and Methods There was a total of 127 patients who underwent chemotherapy for pancreatic cancer between January 2007 and November 2011 at our institution. Patients were treated with either GEM (gemcitabine 1,000 mg/m2 on days 1, 8, and 15 every 4 weeks), GEM-T (gemcitabine 1,000 mg/m2 on days 1 and 8 every 3 weeks and erlotinib 100 mg daily), or GEM-X (gemcitabine 1,000 mg/m2 on days 1 and 8 every 3 weeks and capecitabine 850 mg/m2 twice daily for 2 weeks followed by 1 week’s rest) as the first-line treatment. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and toxicity were evaluated. Results The patient population was divided into groups depending on their first-line treatment: GEM (n=47), GEM-T (n=44), and GEM-X (n=36). GEM-X significantly improved ORR (21.2% vs. 12.7% and 15.9%), PFS (8.9 vs. 5.2 and 3.9 months; p < 0.001), and OS (12.1 vs. 10.4 and 9.9 months; p = 0.03) compared to GEM and GEM-T, respectively. There were higher incidences of some non-hematologic adverse events with GEM-X and GEM-T compared to GEM, but most were grade 1 or 2. Conclusion GEM-X presented better clinical efficacy and acceptable tolerability than GEM-T and GEM in advanced pancreatic cancers. It is worthy to further investigate which agent has a clinical advantage as a combination drug with gemcitabine in pancreatic cancer and to explore the predictive markers leading to personalize anti-cancer treatment.

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Xiao-Yan Liu, Hong-Nian Pan, Yue Yu
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Umme Hani, Riyaz Ali M. Osmani, Ayesha Siddiqua, Shadma Wahab, Sadia Batool, Hissana Ather, Norhan Shereba, Ali Alqahtani
Journal of Drug Delivery Science and Technology.2021; : 102539. CrossRef
Pharmacoeconomic Evaluation of Erlotinib for the Treatment of Pancreatic Cancer
Kunxi Bao, Xiaobing Li, Xiaojing He, Lingyan Jian
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Are ENT1/ENT1, NOTCH3, and miR-21 Reliable Prognostic Biomarkers in Patients with Resected Pancreatic Adenocarcinoma Treated with Adjuvant Gemcitabine Monotherapy?
Lucie Jiraskova, Ales Ryska, Erik Jurjen Duintjer Tebbens, Helena Hornychova, Filip Cecka, Frantisek Staud, Lukas Cerveny
Cancers.2019; 11(11): 1621. CrossRef
Gemcitabine–erlotinib versus gemcitabine–erlotinib–capecitabine in the first-line treatment of patients with metastatic pancreatic cancer: Efficacy and safety results of a phase IIb randomised study from the Spanish TTD Collaborative Group
Antonio Irigoyen, Javier Gallego, Carmen Guillén Ponce, Ruth Vera, Vega Iranzo, Inmaculada Ales, Sara Arévalo, Aleydis Pisa, Marta Martín, Antonieta Salud, Esther Falcó, Alberto Sáenz, José Luis Manzano Mozo, Gema Pulido, Joaquina Martínez Galán, Roberto
European Journal of Cancer.2017; 75: 73. CrossRef
New targeted therapies in pancreatic cancer
Andrada Seicean
World Journal of Gastroenterology.2015; 21(20): 6127. CrossRef

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Changes in the Mean Corpuscular Volume after Capecitabine Treatment Are Associated with Clinical Response and Survival in Patients with Advanced Gastric Cancer: Hyun Ae Jung, Hyun-Jun Kim, Chi Hoon Maeng, Se Hoon Park, Jeeyun Lee, Joon Oh Park, Young Suk Park, Ho Yeong Lim, Won Ki Kang; Cancer Res Treat. 2015;47(1):72-77. Published online August 21, 2014; DOI: https://doi.org/10.4143/crt.2013.172

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Purpose
Capecitabine is known to increase mean corpuscular volume (MCV). To define the incidence of capecitabine-induced macrocytosis and its association with chemotherapy outcomes, we investigated data of 89 patients with advanced gastric cancer (AGC) who were enrolled in a randomized chemotherapy trial involving capecitabine. Materials and Methods Chemotherapy-naïve AGC patients were treated with capecitabine (1,000 mg/m2/day on days 1-14) plus cisplatin (75 mg/m2 on day 1), with or without epirubicin (50 mg/m2 on day 1). Complete blood counts including MCV were measured at baseline and on day 1 of each 3-week chemotherapy course. Macrocytosis was defined as a MCV increase > 10 fL from baseline. Multivariate Cox proportional hazards models were used for analysis of the impact of clinical and MCV values on chemotherapy outcomes. Results At baseline, the mean MCV was 88.2 fL (normal range, 80 to 100 fL). During chemotherapy, MCV increased in a dose-dependent manner with a mean increase of 11.3 fL. MCV elevation after capecitabine treatment in 74 patients (90%) and 44 patients (42%) developed macrocytosis. Results of multivariate analysis showed that development of macrocytosis was independent of baseline hemoglobin level, liver metastasis, performance status, or liver function. The number of chemotherapy cycles showed strong association with development of macrocytosis and hematologic adverse events. In addition, a significant association was observed between macrocytosis and clinical response or survival. Conclusion Macrocytosis developed with more frequent and prolonged use of capecitabine. It is possible that association with treatment outcomes warrants further investigation.

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A Phase II Trial of Gemcitabine plus Capecitabine for Patients with Advanced Pancreatic Cancer: Jong Gwon Choi, Jae Hong Seo, Sang Cheul Oh, Chul Won Choi, Jun Suk Kim; Cancer Res Treat. 2012;44(2):127-132. Published online June 30, 2012; DOI: https://doi.org/10.4143/crt.2012.44.2.127

Abstract PDF PubReader ePub

PURPOSE
The purpose of this study was to determine the efficacy and safety of treatment using gemcitabine and capecitabine for patients with advanced pancreatic cancer.
MATERIALS AND METHODS
Patients with advanced unresectable pancreatic adenocarcinoma were enrolled in the study. Inclusion criteria included no prior systemic chemotherapy or radiation therapy, at least one radiographically documented and measurable tumor lesion, and adequate patient organ functions. The patients received 1,000 mg/m2 gemcitabine intravenously on days 1, 8 and 15, and 830 mg/m2 of oral capecitabine twice a day on days 1-21 of a 28-day cycle.
RESULTS
Fifty patients with a median age of 53 years (range, 39 to 76 years) were enrolled in the study. The median follow-up was 10.0 months. The objective response rate of the 50 patients was 48.0% (95% CI, 22.5 to 57.1%). The median time to progression and overall survival were 6.5 months (95% CI, 2.3 to 8.7 months) and 10.0 months (95% CI, 5.7 to 16.7 months), respectively. Grade 3-4 toxicities associated with chemotherapy included neutropenia (22%), anemia (8%), thrombocytopenia (6%), and hand-foot syndrome (10%).
CONCLUSION
Combination chemotherapy using gemcitabine and capecitabine was well tolerated and demonstrated promising efficacy in the treatment of advanced pancreatic cancer.

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A Retrospective Study of First-Line Combination Chemotherapy in Advanced Colorectal Cancer: A Korean Single-Center Experience: Soon Il Lee, Se Hoon Park, Do Hyoung Lim, Keon Woo Park, Jeeyun Lee, Joon Oh Park, Young Suk Park, Ho Yeong Lim, Won Ki Kang; Cancer Res Treat. 2011;43(2):96-101. Published online June 30, 2011; DOI: https://doi.org/10.4143/crt.2011.43.2.96

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PURPOSE
Fluoropyrimidine-based combination chemotherapy, in combination with either oxaliplatin or irinotecan, has demonstrated efficacy and tolerability in treatment of advanced colorectal cancer (ACC).
MATERIALS AND METHODS
Between January 2006 and December 2007, a total of 478 ACC patients were treated with combination chemotherapy in first-line settings. Combination therapies included: 5-fluorouracil, folinic acid plus oxaliplatin (FOLFOX, n=172), 5-fluorouracil, folinic acid plus irinotecan (FOLFIRI, n=95), capecitabine plus oxaliplatin (XELOX, n=155), and capecitabine plus irinotecan (XELIRI, n=56). FOLFOX and FOLFIRI were repeated every 2 weeks, whereas XELOX and XELIRI were repeated every 3 weeks until occurrence of disease progression or unacceptable toxicity, or until a patient chose to discontinue treatment.
RESULTS
The median age was 58 years (range, 19 to 84 years) and the median chemotherapy durations for FOLFOX, FOLFIRI, XELOX, and XELIRI were 4.9, 4.5, 5.7, and 5.4 months, respectively. Combination chemotherapy regimens were generally well tolerated. The estimated median progression-free-survival (PFS) for all patients was 6.8 months (95% confidence interval, 6.3 to 7.3 months). No statistically significant difference in PFS was found among regimens used as first-line chemotherapy. Sixty percent (n=290) of patients received second or further lines of therapy after failure.
CONCLUSION
Fluoropyrimidine-based combination chemotherapy regimens appear to be equally active and tolerable as first-line therapy for ACC.

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Nineteen-year, real-world experience of first-line combination chemotherapy in patients with metastatic colorectal cancer: a propensity score analysis from southern Thailand
Jirapat Wonglhow, Chirawadee Sathitruangsak, Arunee Dechaphunkul, Patrapim Sunpaweravong
Journal of International Medical Research.2023;[Epub] CrossRef
Polymorphisms in TYMS for Prediction of Capecitabine-Induced Hand-Foot Syndrome in Chinese Patients with Colorectal Cancer
Si-Qi Dong, Tong-Min Wang, Jiang-Bo Zhang, Yong-Qiao He, Wen-Qiong Xue, Zi-Yi Wu, Da-Wei Yang, Lian-Jing Cao, Jing-Wen Huang, Xi-Zhao Li, Pei-Fen Zhang, Xiao-Hui Zheng, Wei-Hua Jia
Cancer Research and Treatment.2021; 53(3): 724. CrossRef

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Predictive Value of the ERCC1 Expression for Treatment Response and Survival in Advanced Gastric Cancer Patients Receiving Cisplatin-based First-line Chemotherapy: Jina Yun, Kyoung-Mee Kim, Seung Tae Kim, Jung-Hoon Kim, Jung A Kim, Jee Hyun Kong, Soo Hyeon Lee, Young-Woong Won, Jong-Mu Sun, Jeeyun Lee, Se Hoon Park, Joon Oh Park, Young Suk Park, Ho Yeong Lim, Won Ki Kang; Cancer Res Treat. 2010;42(2):101-106. Published online June 30, 2010; DOI: https://doi.org/10.4143/crt.2010.42.2.101

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Purpose

The aim of this study was to determine whether the ERCC1 expression is effective to predict the clinical outcomes of patients with advanced gastric cancer (AGC) and who were treated with cisplatin-based first-line chemotherapy.

Materials and Methods

A total of 89 measurable AGC patients received cisplatin and capecitabine, with or without epirubicin, as a part of a randomized phase II study. Patients were included for the current molecular analysis if they had received two or more cycles of chemotherapy, their objective tumor responses were measured and if their paraffin-embedded tumor samples were available. The ERCC1 expression was examined by performing immunohistochemical (IHC) staining, and the patients were divided into two groups (positive or negative) according to the presence of IHC staining of the tumor cell nuclei.

Results

Of the 32 eligible patients, 21 patients (66%) had tumor with a positive expression of ERCC1 and the remaining 11 patients had tumor with a negative ERCC1-expression. The ERCC1-negative patients achieved a higher response rate than that of the ERCC1-positive patients (44% vs. 28%, respectively), although the difference was not statistically significant (p=0.42). The median survival time for the all patients was 14.6 months (95% CI: 13.6 to 15.6 months). The one-year survival rate was similar for the ERCC1-negative patients (61%) and the ERCC1-positive patients (70%).

Conclusion

In the current study, the tumor ERCC1 expression by IHC staining could not predict the clinical response or survival of AGC patients who were treated with cisplatin-based first-line chemotherapy. The ERCC1 protein expression does not appear to be a useful tool for the selection of tailored chemotherapy for these patients.

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Histopathological regression of gastric adenocarcinoma after neoadjuvant therapy: a critical review
Eduardo Henrique Cunha Neves Filho, Rosane Oliveira de Sant'Ana, Luiz Vianney Saldanha Cidrão Nunes, Adriana Pinheiro Bezerra Pires, Maria do Perpétuo Socorro Saldanha da Cunha
APMIS.2017; 125(2): 79. CrossRef
Predictive biomarkers for targeted and cytotoxic agents in gastric cancer for personalized medicine
Shalong Wang, Lianwen Yuan
BioScience Trends.2016; 10(3): 171. CrossRef
Influence of ERCC1 and ERCC4 polymorphisms on response to prognosis in gastric cancer treated with FOLFOX-based chemotherapy
Zheng-mao Lu, Tian-hang Luo, Ming-ming Nie, Guo-en Fang, Li-ye Ma, Xu-chao Xue, Guo Wei, Chong-we Ke, Jian-wei Bi
Tumor Biology.2014; 35(4): 2941. CrossRef
The prognostic value of ERCC1 expression in gastric cancer patients treated with platinum-based chemotherapy: a meta-analysis
Kong-Kong Wei, Lei Jiang, Yao-Yao Wei, Yu-Feng Wang, Xuan-Kun Qian, Qiang Dai, Quan-Lin Guan
Tumor Biology.2014; 35(9): 8721. CrossRef
Predictive value of excision repair cross-complementation group 1 expression for platinum-based chemotherapy and survival in gastric cancer: a meta-analysis
Anqi Yao, You Wang, Xiaohong Peng, Rong Ye, Qiaoli Wang, Yuexiao Qi, Fuxiang Zhou
Journal of Cancer Research and Clinical Oncology.2014; 140(12): 2107. CrossRef
Correlation between expressions of ERCC1/TS mRNA and effects of gastric cancer to chemotherapy in the short term
Liqi Chen, Guoli Li, Jieshou Li, Chaogang Fan, Jian Xu, Bo Wu, Kun Liu, Caihua Zhang
Cancer Chemotherapy and Pharmacology.2013; 71(4): 921. CrossRef
ERCC1 C19007T polymorphism and the risk and invasiveness of cervical cancer in Korean women
Seung‐Su HAN, Jae Weon KIM, Sang Hoon LEE, Dong Ho KIM, Noh‐Hyun PARK, Yong‐Sang SONG, Soon‐Beom KANG
Asia-Pacific Journal of Clinical Oncology.2012;[Epub] CrossRef
Gastric Cancer
Joshua D. Lawson, Jason K. Sicklick, Paul T. Fanta
Current Problems in Cancer.2011; 35(3): 97. CrossRef

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Optimal Timing for the Administration of Capecitabine with Preoperative Chemoradiation for Locally Advanced Rectal Cancer: Young Ju Noh, Won Sik Choi, Jong Hoon Kim, Jin Cheon Kim, Chang Sik Yu, Hee Cheol Kim, Tae Won Kim, Heung Moon Chang, Min Hee Ryu, Seung Do Ahn, Sang-wook Lee, Seong Soo Shin, Jung Eun Lee, Eun Kyung Choi; Cancer Res Treat. 2006;38(1):30-34. Published online February 28, 2006; DOI: https://doi.org/10.4143/crt.2006.38.1.30

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Purpose

Capecitabine is an oral fluoropyrimidine carbamate and it is known as an effective radiosensitizer. Capecitabine and its metabolite reach their peak concentration in the plasma at 1~2 hours after a single oral administration of capecitabine and the levels fall rapidly thereafter. To verify the radiosensitizing effect of capecitabine that is based on such pharmacokinetic characteristics, we performed a retrospective analysis on the optimal timing of capecitabine administration with performing preoperative chemoradiation for locally advanced rectal cancer.

Materials and Methods

Among 171 patients who were treated with preoperative radiotherapy and concurrent capecitabine administration for rectal cancer, 56 patients were administered capecitabine at 1~2 hours before radiotherapy (group A), and at other time in the other 115 patients (group B). Total mesorectal excision was done at 4 to 6 weeks after the completion of chemoradiation. The radiosensitizing effect of capecitabine was evaluated on the basis of the pathological response.

Results

Complete pathological regression of the primary tumor was observed in 12 patients (21.4%) for group A and in 11 patients (9.6%) for group B (p=0.031). Residual disease less than 0.5 cm (a good response) was observed in 19 patients (33.9%) for group A and in 23 patients (20.0%) for group B (p=0.038). On multivariate analysis, the capecitabine ingestion time showed marginal significance.

Conclusion

When performing preoperative chemoradiation for locally advanced rectal cancer, the radiosensitizing effect of capecitabine was enhanced when it was administered 1 hour before radiotherapy.

Citations

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Systematic review of treatment intensification using novel agents for chemoradiotherapy in rectal cancer
R Clifford, N Govindarajah, J L Parsons, S Gollins, N P West, D Vimalachandran
British Journal of Surgery.2018; 105(12): 1553. CrossRef

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Prospective Phase II Study of Preoperative Chemoradiation with Capecitabine in Locally Advanced Rectal Cancer: Jin-hong Park, Jong Hoon Kim, Seung Do Ahn, Sang-wook Lee, Seong Soo Shin, Jin Cheon Kim, Chang Sik Yu, Hee Cheol Kim, Yoon-Koo Kang, Tae Won Kim, Heung Moon Chang, Min Hee Ryu, Eun Kyung Choi; Cancer Res Treat. 2004;36(6):354-359. Published online December 31, 2004; DOI: https://doi.org/10.4143/crt.2004.36.6.354

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Purpose

Capecitabine is an attractive oral chemotherapeutic agent that has a radiosensitizing effect and tumor-selectivity. This study was performed to evaluate the efficacy and toxicity of preoperative chemoradiation therapy, when used with oral capecitabine, for locally advanced rectal cancer.

Materials and Methods

A prospective phase II trial of preoperative chemoradiation for locally advanced adenocarcinomas of the lower two-thirds of the rectum was conducted. A radiation dose of 50 Gy over five weeks and a daily dose of 1650 mg/m² capecitabine in two potions was administered during the entire course of radiation therapy. Surgery was performed with standardized total mesorectal excision four to six weeks after completion of the chemoradiation.

Results

Between January 2002 and September 2003, 61 patients were enrolled onto this prospective phase II trial. The pretreatment clinical stages were T3 in 64% (n=39), T4 in 36% (n=22) and N1-2 in 82% (n=50) of these patients. Fifty-six (92%) patients completed the chemoradiation as initially planned and a complete resection performed in 58 (95%). Down-staging was observed in 45 patients (74%) and a pathologic complete response in 6 (10%). Among the 37 patients with tumors located within 5 cm from the anal verge on colonoscopy, 27 (73%) underwent a sphincter-preserving procedure. No grade 3 and 4 proctitis or hematological toxicities were observed.

Conclusion

Preoperative chemoradiation therapy with capecitabine achieved encouraging rates of tumor downstaging and sphincter preservation, with a low toxicity profile. This combined modality can be regarded as a safe and effective treatment for locally advanced rectal cancer.

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MRI for Rectal Cancer: Staging, mrCRM, EMVI, Lymph Node Staging and Post-Treatment Response
David D.B. Bates, Maria El Homsi, Kevin J. Chang, Neeraj Lalwani, Natally Horvat, Shannon P. Sheedy
Clinical Colorectal Cancer.2022; 21(1): 10. CrossRef
MRI of Rectal Cancer: An Overview and Update on Recent Advances
Kartik S. Jhaveri, Hooman Hosseini-Nik
American Journal of Roentgenology.2015; 205(1): W42. CrossRef
Current Controversies in Neoadjuvant Chemoradiation of Rectal Cancer
P. Terry Phang, Xiaodong Wang
Surgical Oncology Clinics of North America.2014; 23(1): 79. CrossRef
Tailored rectal cancer treatment – a time for implementing contemporary prognostic factors?
A. Wibe, W. L. Law, V. Fazio, C. P. Delaney
Colorectal Disease.2013; 15(11): 1333. CrossRef
Oncologic Outcome After Preoperative Chemoradiotherapy in Patients With Pathologic T0 (ypT0) Rectal Cancer
Tae Young Jang, Chang Sik Yu, Yong Sik Yoon, Seok-Byung Lim, Seung-Mo Hong, Tae Won Kim, Jong Hoon Kim, Jin Cheon Kim
Diseases of the Colon & Rectum.2012; 55(10): 1024. CrossRef
Phase II study of concurrent chemoradiotherapy with capecitabine and cisplatin in patients with locally advanced squamous cell carcinoma of the head and neck
J G Kim, S K Sohn, D H Kim, J H Baek, S B Jeon, Y S Chae, K B Lee, J S Park, J H Sohn, J C Kim, I K Park
British Journal of Cancer.2005; 93(10): 1117. CrossRef
Preoperative Concurrent Chemoradiotherapy with Oral Fluoropyrimidine in Locally Advanced Rectal Cancer: How Good Is Good Enough?
Hyun Cheol Chung
Cancer Research and Treatment.2004; 36(6): 341. CrossRef

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Combination Chemotherapy of Oxaliplatin and Capecitabine in Patients with Metastatic Colorectal 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, Heung Woo Lee; Cancer Res Treat. 2003;35(5):407-410. Published online October 31, 2003; DOI: https://doi.org/10.4143/crt.2003.35.5.407

Abstract PDF

PURPOSE
To evaluate the efficacy and toxicity of oxaliplatin and capecitabine in patients with metastatic colorectal cancer. MATERIALS AND METHODS: Between December 2001 and April 2003, fourteen patients were enrolled in this study. Oxaliplatin, 80 mg/m(2), was administered intravenously on day 1, and capecitabine, 1, 250 mg/m(2) bid po (total daily dose 2, 500 mg/m(2)), was given on days 1~14 of 3 week cycles. RESULTS: The median age of the patients was 57 years (range: 41~74), and the most common sites of metastasis were liver, lung or lymph node. Of the 12 evaluable patients, the overall response rate was 41.7%, but with no complete response. The median response duration and median progression free survival of 12 patients were 42 and 24.4 weeks, respectively. The median overall survival was not reached. A median 6 (range: 1~9), and a total 80, cycles were administered to 14 patients. 80 cycles were evaluable for toxicity. The most common hematological toxicities were NCI grades I/II anemia (45%), leucopenia (33.75%) and thrombocytopenia (17.5%). The most common non-hematological toxicities were nausea/ vomiting (28.75/5%) and neurotoxicity (8.75%). Hand and foot syndrome was noted in only 3.75%. There was no life-threatening toxicity.
CONCLUSION
Oxaliplatin and oral capecitabine combination chemotherapy showed significant activity and favorable toxicity in patients with metastatic colorectal cancer. Further studies, with larger numbers of patients and long-tern follow-up will be needed.

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Case Report: Vision Loss Induced by Capecitabine in Patient with Preexisting Left Eyes Blind
Paul Matte, Michel Ducreux
Case Reports in Oncology.2023; : 480. CrossRef
Phase II study of capecitabine and irinotecan combination chemotherapy in patients with advanced gastric cancer
J H Baek, J G Kim, S B Jeon, Y S Chae, D H Kim, S K Sohn, K B Lee, Y J Choi, H J Shin, J S Chung, G J Cho, H Y Jung, W Yu
British Journal of Cancer.2006; 94(10): 1407. CrossRef

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