Cancer Research and Treatment

Original Articles

Head and Neck cancer

Analysis of Response and Progression Patterns of Tyrosine Kinase Inhibitors in Recurrent or Metastatic Adenoid Cystic Carcinoma: A Post Hoc Analysis of Two KCSG Phase II Trials: Youjin Kim, Bhumsuk Keam, Eun Joo Kang, Jin-Soo Kim, Hye Ryun Kim, Keun-Wook Lee, Jung Hye Kwon, Kyoung Eun Lee, Yaewon Yang, Yoon Hee Choi, Min Kyoung Kim, Jun Ho Ji, Tak Yun, Moon Young Choi, Ki Hyeong Lee, Sung-Bae Kim, Myung-Ju Ahn; Cancer Res Treat. 2024;56(4):1068-1076. Published online April 15, 2024; DOI: https://doi.org/10.4143/crt.2024.008

Abstract PDF Supplementary Material PubReader ePub: Purpose
In this study, we evaluated 66 patients diagnosed with adenoid cystic carcinoma (ACC) enrolled in two Korean Cancer Study Group trials to investigate the response and progression patterns in recurrent and/or metastatic ACC treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs).
Materials and Methods
We evaluated 66 patients diagnosed with ACC who were enrolled in the Korean Cancer Study Group trials. The tumor measurements, clinical data, treatment outcomes, and progression patterns of therapy were analyzed.
Results
In the 66 patients (53 receiving axitinib and 13 receiving nintedanib), the disease control rate was 61%, and three patients achieved partial response. The median follow-up, median progression-free survival (PFS), overall survival, and 6-month PFS rate were 27.6%, 12.4%, and 18.1% months and 62.1%, respectively. Among 42 patients who experienced progression, 27 (64.3%) showed target lesion progression. Bone metastasis was an independent poor prognostic factor.
Conclusion
Overall, most patients demonstrated stable disease with prolonged PFS; however, prominent target lesion progression occurred in some patients. Thus, PFS may capture VEGFR-TKI efficacy better than the objective response rate.

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Genitourinary cancer

Real-World Study Evaluating Safety and Effectiveness of Axitinib in Korean Patients with Renal Cell Carcinoma after Failure of One Prior Systemic Therapy: Sang Joon Shin, Jae Lyun Lee, Tae Gyun Kwon, Byoung Young Shim, Ho Seok Chung, Sang-Hee Kim, Se Hoon Park; Cancer Res Treat. 2023;55(2):643-651. Published online November 28, 2022; DOI: https://doi.org/10.4143/crt.2022.883

Abstract PDF Supplementary Material PubReader ePub

Purpose
This post-marketing surveillance (PMS) study was conducted to monitor the usage of axitinib (Inlyta) in clinical practice of Korean patients with advanced renal cell carcinoma (RCC) with disease progression during or after a prior systemic therapy in real world.
Materials and Methods
In this multicenter, observational study, patients indicated for oral axitinib 5 mg twice daily as second-line therapy for advanced RCC were followed up under routine clinical practices, and their safety and effectiveness outcomes were collected.
Results
Between 2012 and 2021, 125 patients were enrolled, and data from 111 patients were analyzed. Median age was 65 years (range, 30 to 84 years), 81% was male, and 110 (99%) had clear cell RCC. The median daily dose of axitinib was 10 mg (range, 4.36 to 15.95 mg) with a median administration period of 5.6 months (range, 15 to 750 days). Eighty-three percentage of patients experienced any grade of adverse events, 71% of which were related to study treatment, including diarrhea (36%), hypertension (21%), stomatitis (17%), decreased appetite (14%), palmar-plantar erythrodysesthesia syndrome (12%), and asthenia (11%). Most adverse events were generally well tolerated and manageable, with 13% of grade ≥ 3. Axitinib dose reduction was required in 20% of the adverse events and discontinuation in 8%. Median progression-free survival was 12.4 months (95% confidence interval [CI], 9.6 to 18.9). Objective responses were observed in 30% of patients (95% CI, 21 to 39) with 4% of complete response and 26% of partial response.
Conclusion
No new safety signal was found in the present PMS study of Korean RCC patients. Axitinib showed consistent outcomes in terms of effectiveness and safety confirming that the drug is a valid option for second-line therapy in patients with advanced RCC in a real-world setting.

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Axitinib

Reactions Weekly.2024; 1991(1): 45. CrossRef

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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.

Citations

Citations to this article as recorded by

Construction of a hypoxia-immune-related prognostic panel based on integrated single-cell and bulk RNA sequencing analyses in gastric cancer
Cuncan Deng, Guofei Deng, Hongwu Chu, Songyao Chen, Xiancong Chen, Xing Li, Yulong He, Chunhui Sun, Changhua Zhang
Frontiers in Immunology.2023;[Epub] CrossRef
Early TP53 Alterations Shape Gastric and Esophageal Cancer Development
Pranshu Sahgal, Brandon M. Huffman, Deepa T. Patil, Walid K. Chatila, Rona Yaeger, James M. Cleary, Nilay S. Sethi
Cancers.2021; 13(23): 5915. CrossRef
High ELK3 Expression is Associated with the VEGF-C/VEGFR-3 Axis and Gastric Tumorigenesis and Enhances Infiltration of M2 Macrophages
Wang Dazhi, Jiao Zheng, Ren Chunling
Future Medicinal Chemistry.2020; 12(24): 2209. CrossRef
RETRACTED: Long non-coding RNA LINC00978 promotes cell proliferation and tumorigenesis via regulating microRNA-497/NTRK3 axis in gastric cancer
Ju-Yuan Bu, Wei-Ze Lv, Yi-Feng Liao, Xiao-Yu Xiao, Bao-Jun Lv
International Journal of Biological Macromolecules.2019; 123: 1106. CrossRef
RETRACTED ARTICLE: Anti-gastric cancer effect of Salidroside through elevating miR-99a expression
Lin Yang, Yanan Yu, Qi Zhang, Xiaoyu Li, Cuiping Zhang, Tao Mao, Siliang Liu, Zibin Tian
Artificial Cells, Nanomedicine, and Biotechnology.2019; 47(1): 3500. CrossRef
Stomatitis and VEGFR-Tyrosine Kinase Inhibitors (VR-TKIs): A Review of Current Literature in 4369 Patients
Claudia Arena, Giuseppe Troiano, Alfredo De Lillo, Nunzio F. Testa, Lorenzo Lo Muzio
BioMed Research International.2018; 2018: 1. CrossRef
Anti-angiogenic Therapy in Patients with Advanced Gastric and Gastroesophageal Junction Cancer: A Systematic Review
Li-Tzong Chen, Do-Youn Oh, Min-Hee Ryu, Kun-Huei Yeh, Winnie Yeo, Roberto Carlesi, Rebecca Cheng, Jongseok Kim, Mauro Orlando, Yoon-Koo Kang
Cancer Research and Treatment.2017; 49(4): 851. CrossRef
Angiogenesis inhibitors in early development for gastric cancer
Mauricio P. Pinto, Gareth I. Owen, Ignacio Retamal, Marcelo Garrido
Expert Opinion on Investigational Drugs.2017; 26(9): 1007. CrossRef
HER2-induced metastasis is mediated by AKT/JNK/EMT signaling pathway in gastric cancer
Yiseul Choi, Young San Ko, Jin Ju Park, Youngsun Choi, Younghoon Kim, Jung-Soo Pyo, Bo Gun Jang, Douk Ho Hwang, Woo Ho Kim, Byung Lan Lee
World Journal of Gastroenterology.2016; 22(41): 9141. CrossRef

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