Cancer Research and Treatment

Original Articles

The Effect of ZD 1839 (Iressa(R)) in the Treatment of Refractory Non Small Cell Lung Cancer: Yong Tai Kim, Chul Kim, Joo Hyuk Sohn, So Young Park, Soo Young Park, Nae Choon Yu, Young Sam Kim, Se Kyu Kim, Joon Chang, Kil Dong Kim, Kyung Young Chung, Joo Hang Kim; Cancer Res Treat. 2003;35(6):502-506. Published online December 31, 2003; DOI: https://doi.org/10.4143/crt.2003.35.6.502

PURPOSE
The aim of this study was to evaluate the efficacy and the safety of ZD 1839 (Iressa(R)) as a 3rd or 4th line chemotherapy regimen in NSCLC patients who are refractory to a previous chemotherapy regimen. MATERIALS AND METHODS: Twenty-five patients who were refractory to previous chemotherapy were selected for this study. The eligible patients had an ECOG performance status of 0 to 2, and an appropriate end organ function. ZD 1839 (Iressa(R))250 mg/d was orally administered until the patients experienced disease progression or unacceptable toxicity. RESULTS: Twenty-five patients were analyzed. The median age of the patients was 57 years. The response rate was 12.0% with partial responses in 3 patients. Fourteen patients (56%) remained in the stable disease state and 8 patients progressed. The median overall survival was 9.0 months (95% CI 6.7~11.2). The median progression free survival was 3 months (95% CI 2.2~3.8). Hematological toxicities of grade 3 or 4 neutropenia, anemia and thrombocytopenia were absent. Non-hematological toxicities were grade 2 or 3 skin rashes in 10 (40.0%) patients and 1 (4.0%) patient and grade 3 nausea in 3 (12.0%) patients. No patient failed to continue chemotherapy due to any drug-related adverse events.
CONCLUSION
The results suggest that ZD 1839 (Iressa(R)) monotherapy is effective and tolerable as a 3rd or 4th line salvage treatment for NSCLC patients refractory to previous chemotherapy regimens.

Citations

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Serum Carcinoembryonic Antigen as an Index of the Therapeutic Effect of EGFR-TKIs in Patients with Advanced Non-Small Cell Lung Cancer
Jin Hee Park, Sung Bin Kim, Sung Jin Nam, Su Hyeon Jeong, Chul Ho Oak, Tae Won Jang, Maan Hong Jung
Journal of Lung Cancer.2010; 9(2): 97. CrossRef
A review of the benefit–risk profile of gefitinib in Asian patients with advanced non‐small‐cell lung cancer
Keunchil Park, Koichi Goto
Current Medical Research and Opinion.2006; 22(3): 561. CrossRef

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Antitumor Activity of Oxaliplatin, 5-FU and Paclitaxel Given Alone or in Combination with ZD1839 in Human Gastric Carcinoma Cells in vitro: Ji Hyun Jang, Sang Hak Lee, Jin Hyoung Kang, Hee Sik Sun, Kazuto Nishio, Nagahiro Saijo, Hyo Jeong Kuh; Cancer Res Treat. 2002;34(5):372-381. Published online October 31, 2002; DOI: https://doi.org/10.4143/crt.2002.34.5.372

Abstract PDF

PURPOSE
Oxaliplatin (LOHP), 5-FU, and paclitaxel (PTX) are considered highly active against advanced gastric carcinomas, and the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, ZD1839 is considered as a good candidate for the treatment of gastric cancers when given alone or in combination with cytotoxic agents. The present study evaluated the antitumor effects of these agents in SNU-1 human gastric cancer cells either alone or when given as a doublet (i.e., as a cytotoxic-cytostatic combination).
MATERIALS AND METHODS
We selected SNU-1 cells that showed DNA mismatch repair (MMR) deficiency and EGFR overexpression. Growth inhibition was measured by MTT and by direct cell counting and cell cycle distribution by flow cytometry. The combination index (CI) was used to describe synergistic interaction.
RESULTS
The four drugs showed IC50s ranging from 1.81 nM to 13.2microM. MTT assay appeared to underestimate the cytotoxicity of PTX, which was attributed to a significant resistant fraction (32%). LOHP and PTX induced G2/M arrest, 5-FU increased in S phase, and ZD1839 in-creased in G1 in a concentration dependent manner. PTX ZD1839 showed the greatest synergism and LOHP ZD1839 showed a similar result. The cell cycle effect of PTX was potentiated by the coadministration of ZD1839. A previously developed cytostatic TPi model was used to assess the contribution of cell cycle arrest to overall growth inhibition, and 64% and 80% of the overall growth inhibition was attributed to cell cycle arrest for LOHP and PTX, when exposed to 7.55microM and 10 nM for 72 hr, respectively.
CONCLUSION
This study demonstrates the antitumor activity and significant cell cycle arrest effect of ZD1839 against human gastric carcinoma cells and its synergistic interaction with LOHP and PTX. These results provide a preclinical rationale for the clinical development of ZD1839 and its use in combination with LOHP or PTX against human gastric cancers that express EGFR.

Citations

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An efficient and flexible framework for inferring global sensitivity of agent-based model parameters
Daniel R. Bergman, Trachette Jackson, Harsh Vardhan Jain, Kerri-Ann Norton, Nicholas Geard
PLOS Computational Biology.2025; 21(9): e1013427. CrossRef
Connecting Agent-Based Models with High-Dimensional Parameter Spaces to Multidimensional Data Using SMoRe ParS: A Surrogate Modeling Approach
Daniel R. Bergman, Kerri-Ann Norton, Harsh Vardhan Jain, Trachette Jackson
Bulletin of Mathematical Biology.2024;[Epub] CrossRef
A confidence building exercise in data and identifiability: Modeling cancer chemotherapy as a case study
Marisa C. Eisenberg, Harsh V. Jain
Journal of Theoretical Biology.2017; 431: 63. CrossRef

5,817 View
39 Download
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