Response and resistance in a non-small-cell lung cancer patient with an epidermal growth factor receptor mutation and leptomeningeal metastases treated with high-dose gefitinib
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HIV and human papillomavirus (HPV) coinfected patients are at high risk of developing precancerous anal lesions (anal intraepithelial neoplasia) and anal malignancies.1 The natural history (that is, progression and persistence) of HPV-associated lesions is accelerated by HIV-related immunosuppression, which may result in the reactivation of previously acquired HPV infection and loss of control of HPV viral replication.2 The longer life expectancy of these coinfected patients in the era of HAART provides an opportunity for invasive anal carcinoma to develop from its dysplastic precursor.The prognosis of anal squamous cell carcinoma is poor in HIV-positive patients, who often present with advanced tumors.3 The appropriate treatment of patients with advanced anal cancer and HIV infection is uncertain.4 Concomitant radiation therapy and chemotherapy (fluorouracil and mitomycin-C) is the current standard of care for HIV-negative patients with invasive anal carcinoma, and that approach has been investigated and applied successfully in HIV-positive patients with similar anal cancers, particularly those with CD4ϩ T-lymphocyte counts greater than 200 cells/L.5,6 HIV-positive patients with anal cancer treated with HAART tend to fare better than those patients who are not receiving HAART.7 It is prudent to point out that our patient never had an anal Papanicolaou (Pap) test (Fig 3, high-grade dysplastic squamous cells; ThinPrep, Cytyc Corporation, Marlborough, MA).HIV-associated anal carcinoma appears to mirror cervical carcinoma in unscreened women, presenting late in the course of the disease and having a protracted, ultimately fatal, course.8 Screening of HIV-positive patients for anorectal dysplasia and/or malignancy by means of an anal Pap test could save lives.9
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EGFR TKIs have shown promising efficacy in the treatment of leptomeningeal disease.
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- Authors
- Jackman, D. M., Holmes, A. J., Lindeman, N., Wen, P. Y., Kesari, S., Borras, A. M., Bailey, C., de Jong, F., Jänne, P. A., & Johnson, B. E.
- Affiliations
- Brigham and Women's Hospital (US)
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
- Dana-Farber Cancer Institute (US)
- AstraZeneca (United Kingdom) (GB)
- Analytico Medinet BV, Breda, the Netherlands
- Department of Medical Oncology, Dana-Farber Cancer Institute; Department of Medicine, Brigham and Women’s Hospital; Harvard Medical School, Boston, MA
- Venue
- Journal of Clinical Oncology
- Published
- 2006-09-20
- Volume
- 24
- Issue
- 27
- Pages
- 4517-4520
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2126767708
- Cited by
- 260
- References
- 10
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 7 · 2023: 11 · 2022: 7 · 2021: 4 · 2020: 10 · 2019: 4 · 2018: 15 · 2017: 18 · 2016: 31 · 2015: 22 · 2014: 18 · 2013: 26 · 2012: 24
- FWCI
- 7.98
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (R01CA114465, P20CA090578, P20 CA 90578-02, 1K12CA87723-01, K12CA087723)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Surgery › Colorectal and Anal Carcinomas
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Keywords
- non-small cell lung cancer, EGFR mutation, leptomeningeal metastasis, gefitinib, drug resistance, EGFR tyrosine kinase inhibitors
- MeSH terms
- Gefitinib, Antineoplastic Agents, Carcinoma, Non-Small-Cell Lung, Humans, Lung Neoplasms, Male, Meningeal Neoplasms, Middle Aged, Mutation, Quinazolines, Treatment Outcome, Drug Resistance, Neoplasm, Protein Kinase Inhibitors, ErbB Receptors
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