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Head and Neck cancer
Metronomic S-1 Adjuvant Chemotherapy Improves Survival in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma
Yi-Feng Yu, Peng Wu, Rui Zhuo, San-Gang Wu
Cancer Res Treat. 2024;56(4):1058-1067.   Published online February 19, 2024
DOI: https://doi.org/10.4143/crt.2023.1343
AbstractAbstract PDFPubReaderePub
Purpose
This study aimed to investigate the efficacy and safety of using metronomic S-1 adjuvant chemotherapy in locoregionally advanced nasopharyngeal carcinoma (LANPC).
Materials and Methods
We retrospectively collected data on patients diagnosed with LANPC between January 2016 and December 2021. All patients were treated with induction chemotherapy and concurrent chemoradiotherapy with or without metronomic chemotherapy (MC). Toxicities during MC were recorded. The chi-square test, Kaplan-Meier methods, propensity score matching (PSM), and Cox proportional hazards model were used for statistical analyses.
Results
A total of 474 patients were identified, including 64 (13.5%) and 410 (83.5%) patients with or without receiving MC, respectively. Patients who received metronomic S-1 had significantly better 3-year locoregional recurrence-free survival (LRFS) (100% vs. 90.9%, p=0.038), distant metastasis-free survival (DMFS) (98.5% vs. 84.1%, p=0.002), disease-free survival (DFS) (98.4% vs. 77.5%, p < 0.001), and overall survival (OS) (98.0% vs. 87.7%, p=0.008) compared to those without metronomic S-1. The multivariate prognostic analysis revealed that metronomic S-1 was identified as an independent prognostic factor associated with better DMFS (hazard ratio [HR], 0.074; p=0.010), DFS (HR, 0.103; p=0.002) and OS (HR, 0.127; p=0.042), but not in LRFS (p=0.071). Similar results were found using PSM. Common adverse events observed in the metronomic S-1 group included leukopenia, neutropenia, increased total bilirubin, anorexia, rash/desquamation, and hyperpigmentation. All patients with adverse events were grade 1-2.
Conclusion
It is worth conducting a randomized controlled trial to assess the effect of metronomic S-1 on survival outcomes and toxicities of LANPC.

Citations

Citations to this article as recorded by  
  • Reply to Commentary on “Metronomic S-1 Adjuvant Chemotherapy Improves Survival in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma”
    San-Gang Wu
    Cancer Research and Treatment.2025; 57(1): 291.     CrossRef
  • Commentary on “Metronomic S-1 Adjuvant Chemotherapy Improves Survival in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma”
    Erkan Topkan, Efsun Somay, Nilufer Kılıc Durankus, Ugur Selek
    Cancer Research and Treatment.2025; 57(1): 289.     CrossRef
  • Short-term versus long-term metronomic adjuvant chemotherapy in locally advanced nasopharyngeal carcinoma: A propensity score-matched real-world study
    Shuhui Dong, Weixin Bei, Lanfeng Lin, Yaofei Jiang, Nian Lu, Guoying Liu, Yanqun Xiang, Weixiong Xia
    Oral Oncology.2024; 156: 106908.     CrossRef
  • 1,976 View
  • 118 Download
  • 1 Web of Science
  • 3 Crossref
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Breast cancer
A Phase II Trial of S-1 and Oxaliplatin in Patients with Metastatic Breast Cancer Previously Treated with Anthracycline and Taxane (KCSG-BR07-03)
Dae-Won Lee, Bhumsuk Keam, Keun Seok Lee, Jin-Hee Ahn, Joohyuk Sohn, Jin Seok Ahn, Moon Hee Lee, Jee Hyun Kim, Kyung Eun Lee, Hyo Jung Kim, Si-Young Kim, Yeon Hee Park, Chan-Young Ock, Kyung-Hun Lee, Sae-Won Han, Sung-Bae Kim, Young Hyuck Im, Hyun Cheol Chung, Do-Youn Oh, Seock-Ah Im
Cancer Res Treat. 2023;55(2):523-530.   Published online November 8, 2022
DOI: https://doi.org/10.4143/crt.2022.1360
AbstractAbstract PDFPubReaderePub
Purpose
This single-arm phase II trial investigate the efficacy and safety of S-1 plus oxaliplatin (SOX) in patients with metastatic breast cancer.
Materials and Methods
Patients with metastatic breast cancer previously treated with anthracyclines and taxanes were enrolled. Patients received S-1 (40-60 mg depending on patient’s body surface area, twice a day, day 1-14) and oxaliplatin (130 mg/m2, day 1) in 3 weeks cycle until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumor 1.1. Secondary endpoints included time-to-progression (TTP), duration-of-response (DoR), overall survival (OS), and adverse events.
Results
A total of 87 patients were enrolled from 11 institutions in Korea. Hormone receptor was positive in 54 (62.1%) patients and six (6.9%) had human epidermal growth factor receptor 2–positive disease. Forty-eight patients (85.1%) had visceral metastasis and 74 (55.2%) had more than three sites of metastases. The ORR of SOX regimen was 38.5% (95% confidence interval [CI], 26.9 to 50.0) with a median TTP of 6.0 months (95% CI, 5.1 to 6.9). Median DoR and OS were 10.3 months (95% CI, 5.5 to 15.1) and 19.4 (95% CI, not estimated) months, respectively. Grade 3 or 4 neutropenia was reported in 28 patients (32.1%) and thrombocytopenia was observed in 23 patients (26.6%).
Conclusion
This phase II study showed that SOX regimen is a reasonable option in metastatic breast cancer previously treated with anthracyclines and taxanes.

Citations

Citations to this article as recorded by  
  • Unraveling the immune landscape and therapeutic biomarker PMEPA1 for oxaliplatin resistance in colorectal cancer: A comprehensive approach
    Zhengguang Zhang, Tianming Lu, Zhe Zhang, Zixian Liu, Ruoning Qian, Ruogu Qi, Fuqiong Zhou, Min Li
    Biochemical Pharmacology.2024; 222: 116117.     CrossRef
  • Efficacy and safety of utidelone plus capecitabine in advanced first-line therapy for metastatic breast cancer: A multicenter real-world study
    Pingping Bi, Xi Wang, Rui Liu, Xiuqin Li, Shanrong Wei, Jiawen Zhao, Xin Tan, Fan Zhang, Qing Mao, Ying Zhang, Baoyan Tang, Xueqiong Xun, Rong Guo, Kai Zheng, Shaoqiang Zhou, Shicong Tang
    Surgery Open Science.2023; 16: 171.     CrossRef
  • 4,866 View
  • 170 Download
  • 2 Web of Science
  • 2 Crossref
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S-1 Based Doublet as an Adjuvant Chemotherapy for Curatively Resected Stage III Gastric Cancer: Results from the Randomized Phase III POST Trial
Choong-kun Lee, Minkyu Jung, Hyo Song Kim, Inkyung Jung, Dong Bok Shin, Seok Yun Kang, Dae Young Zang, Ki Hyang Kim, Moon Hee Lee, Bong-Seog Kim, Kyung Hee Lee, Jae-Ho Cheong, Woo Jin Hyung, Sung Hoon Noh, Hyun Cheol Chung, Sun Young Rha
Cancer Res Treat. 2019;51(1):1-11.   Published online February 5, 2018
DOI: https://doi.org/10.4143/crt.2018.028
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
We conducted a randomized, multicenter, phase III trial to compare S-1 plus docetaxel (DS) with S-1 plus cisplatin (SP) as adjuvant chemotherapy for stage III gastric cancer patients.
Materials and Methods
Stage III gastric cancer patients who had received curative gastrectomy with D2 lymphadenectomy were randomized into equal groups to receive adjuvant chemotherapy of eight cycles of DS (S-1 70 mg/m2 /day on days 1-14 plus docetaxel 35 mg/m2 on days 1 and 8) every 3 weeks or SP (S-1 70 mg/m2 /day on days 1-14 plus cisplatin 60 mg/m2 on day 1) every 3 weeks. The primary endpoint was 3-year disease-free survival (DFS) rate.
Results
Between November 2010 and July 2013, 153 patients (75 patients to DS and 78 patients to SP) were enrolled from 8 institutions in Korea. After the capecitabine plus oxaliplatin was approved based on the CLASSIC study, itwas decided to close the study early. With a median follow-up duration of 56.9 months, the 3-year DFS rate between two groups was not significantly different (49.14% in DS group vs. 52.5% in SP group). The most common grade 3-4 adverse event was neutropenia (42.7% in DS and 38.5% in SP, p=0.351). SP group had more grade 3-4 anemia (1.3% vs. 11.5%, p=0.037), whereas grade 3-4 hand-foot syndrome (4.1% vs. 0%, p=0.025) and mucositis (10.7% vs. 2.6%, p=0.001) were more common in DS group. Fifty-one patients (68%) in DS group and 52 (66.7%) in SP group finished planned treatment.
Conclusion
Our findings suggest that SP or DS is an effective and tolerable option for patients with curatively resected stage III gastric cancer.

Citations

Citations to this article as recorded by  
  • Efficacy and safety of docetaxel plus S-1-based therapy in gastric cancer: a quantitative evidence synthesis of randomized controlled trials
    Hui-Fen Lv, Li-Feng Qin, Rui-Zhi Ran, Xue-Ping Jiang, Fang-Yu Zhao, Bo Li
    Frontiers in Pharmacology.2024;[Epub]     CrossRef
  • A novel method of bedside hyperthermic intraperitoneal chemotherapy as adjuvant therapy for stage-III gastric cancer
    Lili Liu, Li Sun, Ning Zhang, Cheng-gong Liao, Haichuan Su, Jie Min, Yang Song, Xue Yang, Xiaofeng Huang, Dongxu Chen, Yu Chen, Hong-wei Zhang, Helong Zhang
    International Journal of Hyperthermia.2022; 39(1): 239.     CrossRef
  • Comment on “post-discharge oral nutritional supplements with dietary advice in patients at nutritional risk after surgery for gastric cancer: A randomized clinical trial”
    Qiang Hu, Yuanshui Sun
    Clinical Nutrition.2021; 40(3): 1438.     CrossRef
  • THE ROLE OF ADJUVANT CHEMOTHERAPY IN THE TREATMENT OF LOCALLY ADVANCED GASTRIC CANCER
    A. A. Bobryshev, M. M. Davudov, M. N. Narimanov, S. B. Polycarpova, V. Y. Kirsanov, V. N. Blindar
    Siberian journal of oncology.2021; 20(1): 133.     CrossRef
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    Kotaro Sugawara, Yoshikuni Kawaguchi, Yasuyuki Seto, Jean-Nicolas Vauthey
    Surgical Oncology.2021; 38: 101599.     CrossRef
  • Surgery alone, adjuvant tegafur/gimeracil/octeracil (S-1), or platinum-based chemotherapies for resectable gastric cancer: real-world experience and a propensity score matching analysis
    Chih-Chieh Yen, Yan-Shen Shan, Ying-Jui Chao, Ting-Kai Liao, I-Shu Chen, Hsuan-Yi Huang, I-Ting Liu, Chia-Jui Yen
    BMC Cancer.2021;[Epub]     CrossRef
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    Ina Valeria Zurlo, Michele Basso, Antonia Strippoli, Maria Alessandra Calegari, Armando Orlandi, Alessandra Cassano, Mariantonietta Di Salvatore, Giovanna Garufi, Emilio Bria, Giampaolo Tortora, Carlo Barone, Carmelo Pozzo
    Cancers.2020; 12(7): 1749.     CrossRef
  • A systematic review and network meta-analysis protocol of adjuvant chemotherapy regimens for resected gastric cancer
    Long Ge, Liangying Hou, Qingxia Yang, Yiting Wu, Xiue Shi, Jiang Li, Kehu Yang
    Medicine.2019; 98(7): e14478.     CrossRef
  • Prognostic and Predictive Factors for the Curative Treatment of Esophageal and Gastric Cancer in Randomized Controlled Trials: A Systematic Review and Meta-Analysis
    Tom van den Ende, Emil ter Veer, Rosa M. A. Mali, Mark I. van Berge Henegouwen, Maarten C. C. M. Hulshof, Martijn G. H. van Oijen, Hanneke W. M. van Laarhoven
    Cancers.2019; 11(4): 530.     CrossRef
  • COMplot, A Graphical Presentation of Complication Profiles and Adverse Effects for the Curative Treatment of Gastric Cancer: A Systematic Review and Meta-Analysis
    Tom van den Ende, Frank A. Abe Nijenhuis, Héctor G. van den Boorn, Emil ter Veer, Maarten C. C. M. Hulshof, Suzanne S. Gisbertz, Martijn G. H. van Oijen, Hanneke W. M. van Laarhoven
    Frontiers in Oncology.2019;[Epub]     CrossRef
  • Cutting-edge evidence of adjuvant treatments for gastric cancer
    Dai Shimizu, Mitsuro Kanda, Yasuhiro Kodera, Junichi Sakamoto
    Expert Review of Gastroenterology & Hepatology.2018; 12(11): 1109.     CrossRef
  • 13,267 View
  • 591 Download
  • 22 Web of Science
  • 11 Crossref
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Multicenter Phase II Study of Oxaliplatin, Irinotecan, and S-1 as First-line Treatment for Patients with Recurrent or Metastatic Biliary Tract Cancer
Changhoon Yoo, Boram Han, Hyeong Su Kim, Kyu-pyo Kim, Deokhoon Kim, Jae Ho Jeong, Jae-Lyun Lee, Tae Won Kim, Jung Han Kim, Dae Ro Choi, Hong Il Ha, Jinwon Seo, Heung-Moon Chang, Baek-Yeol Ryoo, Dae Young Zang
Cancer Res Treat. 2018;50(4):1324-1330.   Published online January 8, 2018
DOI: https://doi.org/10.4143/crt.2017.526
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Although gemcitabine plus cisplatin has been established as the standard first-line chemotherapy for patients with advanced biliary tract cancer (BTC), overall prognosis remains poor. We investigated the efficacy of a novel triplet combination of oxaliplatin, irinotecan, and S-1 (OIS) for advanced BTC.
Materials and Methods
Chemotherapy-naive patientswith histologically documented unresectable or metastatic BTC were eligible for this multicenter, single-arm phase II study. Patients received 65 mg/m2 oxaliplatin (day 1), 135 mg/m2 irinotecan (day 1), and 40 mg/m2 S-1 (twice a day, days 1-7) every 2 weeks. Primary endpoint was objective response rate. Targeted exome sequencing for biomarker analysis was performed using archival tissue.
Results
In total, 32 patients were enrolled between October 2015 and June 2016. Median age was 64 years (range, 40 to 76 years), with 24 (75%) male patients; 97% patients had metastatic or recurrent disease. Response rate was 50%, and median progression-free survival and overall survival (OS) were 6.8 months (95% confidence interval [CI], 4.8 to 8.8) and 12.5 months (95% CI, 7.0 to 18.0), respectively. The most common grade 3-4 adverse events were neutropenia (32%), diarrhea (6%), and peripheral neuropathy (6%). TP53 and KRAS mutations were the most frequent genomic alterations (42% and 32%, respectively), and KRAS mutations showed a marginal relationship with worse OS (p=0.07).
Conclusion
OIS combination chemotherapy was feasible and associated with favorable efficacy outcomes as a first-line treatment in patients with advanced BTC. Randomized studies are needed to compare OIS with gemcitabine plus cisplatin.

Citations

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    Hui-Jen Tsai, Shih-Hung Yang, Chin-Fu Hsiao, Hsiang-Fong Kao, Yung-Yeh Su, Yan-Shen Shan, Chia-Jui Yen, Jeng-Shiun Du, Chiun Hsu, I-Chen Wu, Li-Tzong Chen
    The Oncologist.2024; 29(10): e1396.     CrossRef
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    Hyehyun Jeong, Bum Jun Kim, Choong-kun Lee, Inkeun Park, Dae Young Zang, Hye Jin Choi, Sang Soo Lee, Do Hyun Park, Tae Jun Song, Dongwook Oh, Sung-Hoon Moon, Kyu-pyo Kim, Zev Wainberg, Baek-Yeol Ryoo, Changhoon Yoo
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S-1–Induced Lacrimal Drainage Obstruction and Its Association with Ingredients/Metabolites of S-1 in Tears and Plasma: A Prospective Multi-institutional Study
Namju Kim, Jin Won Kim, Je-Hyun Baek, Jin-Soo Kim, Ho-Kyung Choung, Tae-Yong Kim, Kyung-Hun Lee, Yung-Jue Bang, Sang In Khwarg, Sang-Hoon Ahn, Do Joong Park, Hyung-Ho Kim, Jae-Yong Chung, Soyeon Ahn, Keun-Wook Lee
Cancer Res Treat. 2018;50(1):30-39.   Published online February 27, 2017
DOI: https://doi.org/10.4143/crt.2016.569
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This prospective study was conducted to determine the incidence of lacrimal drainage obstruction (LDO) during S-1 chemotherapy and evaluate the association between the development of LDO and the concentrations of ingredients/metabolites of S-1 in tears and plasma.
Materials and Methods
A total of 145 patients with gastric cancer who received adjuvant S-1 therapy were enrolled. Ophthalmologic examinations were performed regularly during S-1 chemotherapy. Concentrations of tegafur, 5-chloro-2,4-dihydroxypyridine (CDHP), and 5-fluorouracil at steady-state trough level were measured in both tears and plasma.
Results
Fifty-three patients (37%) developed LDO. The median time to the onset of LDO was 10.9 weeks, and LDO developed most frequently in the nasolacrimal duct. Univariable analyses revealed that an older age (≥ 70 years), creatinine clearance rate (Ccr) < 80 mL/min, 5-fluorouracil concentration in plasma ≥ 22.3 ng/mL (median), CDHP concentration in plasma ≥ 42.0 ng/mL (median), and tegafur concentration in tears ≥ 479.2 ng/mL (median) were related to increased development of LDO. Multivariable analysis indicated that a high plasma 5-fluorouracil concentration was predictive of increased development of LDO (hazard ratio, 2.02; p=0.040), along with older age and decreased Ccr. Patients with LDO also developed S-1–related non-hematologic toxicity more frequently than those without LDO (p=0.016).
Conclusion
LDO is a frequent adverse event during S-1 chemotherapy. An older age, decreased Ccr, and high plasma 5-fluorouracil concentration were found to be independent risk factors for LDO. The high incidence of LDO warrants regular ophthalmologic examination and early intervention in patients receiving S-1 therapy.

Citations

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    Jeremy Chung Bo Chiang, Ilyanoon Zahari, Maria Markoulli, Arun V. Krishnan, Susanna B. Park, Annalese Semmler, David Goldstein, Katie Edwards
    The Ocular Surface.2020; 18(3): 403.     CrossRef
  • Pharmacokinetics of S-1 monotherapy in plasma and in tears for gastric cancer patients
    Hirofumi Yasui, Takeshi Kawakami, Hiroya Kashiwagi, Keita Mori, Katsuhiro Omae, Jun Kasai, Kunihiro Yoshisue, Masahiro Kawahira, Takahiro Tsushima, Nozomu Machida, Akira Fukutomi, Ken Yamaguchi
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Phase II Study of S-1 Plus Either Irinotecan or Docetaxel for Non-small Cell Lung Cancer Patients Treated with More Than Three Lines of Treatment
Dal Yong Kim, Dae Ho Lee, Sun-Joo Jang, Sang-We Kim, Cheolwon Suh, Jung Shin Lee
Cancer Res Treat. 2011;43(4):212-216.   Published online December 27, 2011
DOI: https://doi.org/10.4143/crt.2011.43.4.212
AbstractAbstract PDFPubReaderePub
PURPOSE
This study was designed to evaluate the efficacy of a combination treatment of S-1 plus either irinotecan or docetaxel for advanced/metastatic non-small cell lung cancer (NSCLC) patients who have already failed 3 or more lines of treatment.
MATERIALS AND METHODS
This was a prospective single center phase II study. The eligible patients received S-1 40 mg/m2 twice a day orally on days 1 though 14 combined with irinotecan 150 mg/m2on D1 only or docetaxel 35 mg/m2 on D1 and D8. The treatment was repeated every 3 weeks until disease progression, unacceptable toxicity, or patient refusal. The choice between the two regimens was made at the discretion of the treating physician.
RESULTS
A total of 14 patients participated in the study. There were 3 patients with squamous cell carcinoma, 9 with adenocarcinoma, and 2 with NSCLC, NOS. Eight of the patients were male. There were 8 patients with an Eastern Cooperative Oncology Group (ECOG) of 1, and 6 patients with an ECOG of 2. All the patients had already been treated with platinum-based chemotherapy and epidermal growth factor receptor tyrosine kinase inhibitor therapy. Out of the 14 patients, 10 received irinotecan and S-1 and the other 4 received docetaxel and S-1. Twelve patients had also received pemetrexed. Disappointingly, there were no response from 2 patients with a stable disease, and therefore, as per the protocol, we stopped the study early. With a median follow-up time of 49 months, the median survival time was 5.6 months (95% confidence interval, 4.3 to 6.9 months).
CONCLUSION
S-1 containing doublets did not show activity in this population as a salvage treatment and further investigation cannot be recommended.

Citations

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  • Docetaxel Nanotechnology in Anticancer Therapy
    Pengxiang Zhao, Didier Astruc
    ChemMedChem.2012; 7(6): 952.     CrossRef
  • 9,397 View
  • 47 Download
  • 1 Crossref
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An Immunohistochemical Study on Differential Diagnosis of Small Round Cell Tumor
Joon Mee Kim, Mi Kyung Shin, Seung Yong Paik, In Sun Kim
J Korean Cancer Assoc. 1990;22(1):48-61.
AbstractAbstract PDF
Small round cell tumors in surgical pathology are difficult to be differentiated each other only by routine H & E stain. In this study we applied six antibodies (keratin, vimentin, neuron-specific enolase, S-100 protein, myoglobin and leukocyte common antigen) as a panel marker to 18 cases of primitive neuroectodermal tumor including neuroblastoma, Ewirig's sarcoma, rhabdomyosarcoma, lymphoma, and small cell carcinoma. The results were summerized as follows: I) Primitive neuroectodermal tumor (PNET) and neuroblastoma showed positive reaction for S -100 protein and neuron-specific enolase (NSE). 2) Ewing's sarcomas showed vimentin positivity with occasional positive reaction for NSE and S -100 protein, but it was always negative for myoglobin. 3) Myoglobin was a specific marker for rhabdomyosarcoma, and vimentin might be positive. In myoglobin negative case, immunostaining for desmin was recommended. 4l Leukocyte common antigen positivity always indicated lymphoma. Occasionally vimentin and NSE were positive. 5) In the cases of carcinoma, keratin was positive and occasionally NSE and/or vimentin were positive.
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In Vitro Chemosencitivity of Doxorubicin on Human Cancer Cell Lines
Chung Gyu Park, Dong Kyun Lim, Yoon Hoh Kook, Chang Yong Cha, Chul Gi Paik
J Korean Cancer Assoc. 1990;22(1):61-66.
AbstractAbstract PDF
The anticancer effect of doxorubicin was evaluated on human cancer cell lines (K562, KATOIII, PC-14, HeLa, SNU-C5, NCI-H417 and Nalm-6) after exposure to doxorubicin at 5, 50, 500 ng/ml for 1 hour at 37`C using in vitro agar-methylcellulose clonogenic assay. The drug concentration which produced 50g inhibition of colony formation (ID) of each cell line were as follows: K562, 258.2 (ng/ml); KATO IIL, 473 (ng/ml); PC-14, 268.5 (ng/ml); HeLa, 355.7 (ng/ ml), SNU-C5, 241.5 (ng/ml); NCI-H417, 13 (ng/ml); Nalm-6, 20 (ng/ml). From this assay NCI-H417 and Nalm-6 were considered to be sensitive to doxorubicin on the basis of the fact that the ID,. for these cell lines was within a clinically achievable range.
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