CNS metastases from colorectal cancer are an uncommon occurrence, with an estimated incidence of 1% to 3%. - Similarly, the presence of leptomeningeal disease (LMD) is also distinctly uncommon, although there are no precise estimates of its incidence. The development of CNS metastases from colorectal cancer usually occurs late in the clinical course and carries a very poor prognosis., In our experience, LMD from colorectal cancer in particular is associated with a sharp decline in clinical status and a dismal short-term prognosis. The treatment of LMD in solid tumors comprises a combination of focal irradiation of symptomatic areas or areas of bulky disease with intrathecal chemotherapy and/or systemic chemotherapy to control active systemic disease.

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To date, the optimal regimen has not been defined and therapeutic outcomes remain poor.,, Here, we present a case report of a patient treated for LMD with bevacizumab, temozolomide, and irinotecan. He was a 49-year-old man who underwent initial treatment for rectal cancer between 1997 and mid-1999. He underwent surgical resection for a T2N0 lesion, with rapid recurrence of the primary tumor. He was treated with subsequent preoperative fluorouracil (FU), radiotherapy, and re-resection, and intraoperative brachytherapy and adjuvant bolus FU and leucovorin. He then remained free of disease until October 2005, when he underwent resection of a right cerebellar mass, which revealed metastatic rectal cancer. At that time, he was also found to have biopsy proven metastatic rectal cancer to mediastinal lymph nodes. In December 2005, he was treated with the FOLFIRI regimen (irinotecan 180 mg/m 2, FU 400 mg/m 2, and leucovorin 400 mg/m 2 on day 1, continuous infusion of FU 1,200 mg/m 2 day 1 through 2) administered every 14 days.

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After two cycles of FOLFIRI therapy, repeat imaging demonstrated slight improvement in mediastinal lymphadenopathy. However, further imaging revealed recurrent disease at the surgical site as well as new LMD, without focal bulky areas, throughout the brain and spinal cord. He was treated with whole-brain radiation therapy down to the C2 vertebrae for a total of 30 Gy over 10 fractions. Preliminary data provided by Friedman (H.S. Friedman, personal communication, January 2006) and subsequently presented in abstract form suggested that bevacizumab could be safely administered in the setting of primary brain tumors. Furthermore, temozolomide was known to have modest activity in brain metastases from solid malignancies. - The patient's systemic disease had also responded to initial irinotecan-based therapy and there were additional data that the combination of temozolomide and irinotecan was both safe and effective.