Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL, USA
*E-mail: jvillano@medicine.bsd.uchicago.edu
ZD1839 (Iressa) is a synthetic, oral anilinoquinazoline with submicromolar specificity for the epidermal growth factor receptor (EGFR). In non-small-cell lung cancer (NSCLC), ZD1839 has shown significant antitumor activity, even in heavily pretreated patients. We present a patient with NSCLC who has brain metastases and was enrolled in hospice care prior to therapy with ZD1839, which produced a sustained clinical response.
A 60-year-old woman was diagnosed with metastatic adenocarcinoma of the lung in March 1999 when she presented with visual auras. A magnetic resonance imaging (MRI) scan of the brain demonstrated three enhancing brain lesions and a computed tomography scan of the chest revealed a 2.5 x 3.5 cm left lung mass. Pathology samples from bronchoscopy and craniotomy confirmed metastatic adenocarcinoma. She was treated with whole brain radiotherapy followed by stereotactic radiosurgery, which effectively treated any residual brain lesions. Her treatments were well tolerated. She then received a phase I/II study treatment of an alternating schedule of docetaxol, gemcitabine, cisplatin and vinorelbine on a 28-day cycle [1]. She received four full cycles of treatment from May to October 1999. Her left chest lesion reduced in size to 1.5 x 1.5 cm and persisted as the only known site of active disease. She then received regional chest radiotherapy in November 1999 of 55 Gy.
She was then monitored without therapy. She presented 8 months after her last treatment with recurrence of auras in July 2000. New brain lesions were detected by a brain MRI scan. These increased in size over the next 5 months, leading to a second stereotactic radiosurgery. Her left chest lesion had remained stable in size since the chest radiotherapy.
In October 2001, imaging studies demonstrated three new brain lesions (Figure 1A), the largest being in the left parietal lobe. She complained of new neurological symptoms of numbness and tingling on the right arm and face with gait instability. She had received the maximal dose of cranial radiotherapy, preventing further palliative radiation treatments. She was placed on steroids, and in a span of 3 months her disease progressed. When she developed difficulties with gait, speech and self-care, she was placed in hospice support. She qualified for compassionate care, and although bedridden, elected to start on ZD1839 at 250 mg daily after two loading doses.
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This is the first clinical report to demonstrate that ZD1839 has anticancer activity in the brain. ZD1839 has excellent cell penetration and based on its chemical structure and low molecular weight probably crosses the bloodbrain barrier [2]. A single preclinical study in mice has shown that ZD1839 retains therapeutic activity on intracranial tumors that over-express EGFR [3]. Our results, therefore, may not be unexpected, but clinical documentation is needed.
The advantages of an oral, non-toxic therapy are immeasurable. Our patient, being bedridden and completely disabled, would neither have been offered nor probably received benefit from traditional chemotherapy. ZD1839 is non-myelosuppressive, as EGFR is not expressed in cells of hematopoietic origin, making it suitable for chronic therapy [4]. From phase I studies, the common side-effects of grade I/II skin rash, diarrhea, and nausea and vomiting have proved tolerable [5]. As EGFR is over expressed in the majority of NSCLC cases, we recommend consideration of a treatment trial with ZD1839, or a close analog with antiEGFR activity, prior to hospice placement.
J. L. Villano*, A. M. Mauer & E. E. Vokes
Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL, USA (*E-mail: jvillano{at}medicine.bsd.uchicago.edu)
References
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