Temodal in the
treatment of brain metastasis of mammary origin
A 63 years old Caucasian lady was diagnosed with invasive grade 2 ductal adenocarcinoma of the left breast with extensive ductal carcinoma in situ, with positive multiple axillary lymph nodes (T2N3) . Hormonal receptor status were negative for both estrogen and progestrero. Her2/neu score was overexpressed (+3). Surgical treatment in the form of modified radical mastectomy was performed on September 21st 1995. This was followed by adjuvant chemotherapy with adriamycin and cytoxan for 4 cycles. After about 6 months surgical reconstruction of the breast was done. Four and half years later in February 2000, she developed metastases in the mediastinum, bones and liver, for which she started treatment with taxol {60 mg/m2 on weekly bases} and herceptin {2 mg/kg weekly} in addition to aredia {90 mg monthly}. A follow-up CT scan after 2 months (22/4/00) showed disappearance of the mediastinal lymph nodes, hepatic lesions and pleural effusion. Taxol was given in total for 31 weeks and stopped due to peripheral neuropathy, while trastuzamab and pamidronate were continued thereafter. Follow-up scans till March 2001 revealed maintenance of her almost complete remission.In July 2001 she started to complain of gait disturbance, inspite of absence of symptoms of increased intracranial pressure. MRI revealed multiple cerebral and cerebellar tiny lesions. Accordingly, she received whole brain irradiation 40 Gy/ 20 fractions / 4 weeks on 6 MV Linear, concomitantly with temodal 75 mg/ m2/ day.A follow-up CT scan after 2 months (22/9/2001) revealed almost complete disappearance of her brain lesions.The patient was maintained on weekly herceptin and temodal 200 mg/ m2/ day for 5 consecutive days every 3 - 4 weeks.A follow-up CT scan (20/12/2001) revealed marvelous theraputic response with only residual right parietal cortical and few left cerebellar lesions.The patient was maintained on the same treatment till 13/8/2002 when she developed progressive pleural effusion. She was shifted to carboplatin/navelbine with herceptin but unfortunately progressed again and was maintained on best supportive care till she died in July 2003.
Discussion: Experiments in cell culture with human glioblastoma cell lines showed that combined treatment of the cultures with temodal and radiotherapy had an additive effect [1]. An earlier report demonstrated a 30% response rate in patients treated with temodal before radiation [2]. Treatment with temodal (75 mg/ m2 daily x 6 weeks) and radiation after surgery or biopsy as initial therapy for newly diagnosed glioblastoma is currently evaluated by Stupp and coworkers at the University of Lausanne and Geneva [3] and by Newlands et al. in London [4]. Preliminary results suggest that this approach is feasible and promising.Our cases show that combining temodal with radiotherapy in cases of brain metastasis from the breast could have an additive effect and better patient’s outcome.
1. Wedge SR, Porteous JK, Glaser MG, et al: In vitro evaluation of temozolomide combined with X-irradiation. Anticancer Drugs 8:92-7, 1997.
2. Newlands ES, O'Reilly SM, Glaser MG, et al: The Charing Cross Hospital experience with temozolomide in patients with gliomas. Eur J Cancer 32A:2236-41, 1996.
3. Stupp R, Dietrich P, Mirimanoff R, et al: Experience with concomitant and adjuvant temozolomide and radiation in newly diagnosed glioblastoma multiforme. Proc Am Soc Clin Oncol, 1999.
4. Brock CS, Newlands ES, Wedge SR, et al: Phase I trial of temozolomide using an extended continuous oral schedule. Cancer Res 58:4363-7, 1998.
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