my personal edition > lymphomas > news


  E-Mail this DGDispatch to a colleague

DGDispatch

High-Dose Methotrexate for Elderly Patients With Newly Diagnosed Primary Central Nervous System Lymphoma: Presented at ICML

By Chris Berrie

LUGANO, SWITZERLAND -- June 17, 2005 -- High-dose methotrexate treatment appears to result in high rates of progression-free survival and overall survival with modest toxicity in elderly patients with newly diagnosed primary central nervous system (CNS) lymphoma, according to a study presented here on June 10^th at the 9^th International Conference on Malignant Lymphoma (ICML).

Jay-Jiguang Zhu, MD, PhD, neuro-oncology fellow at the Pappas Centre for Neuro-Oncology, Massachusetts General Hospital Cancer Center, Boston, Massachusetts, United States, presented the findings.

Although whole-brain radiotherapy can provide response rates above 90% in patients with CNS lymphoma, this treatment is associated with high rates of relapse and delayed neurotoxicity that is particularly pronounced in elderly patients.

"The objective of this study is to identify elderly patients aged 70 or above who are diagnosed with primary CNS lymphoma to see their response to the treatment, as well as the toxicities to the treatment, which is high-dose methotrexate IV."

For this study, Dr. Zhu and colleagues identified 27patients (median age, 73; range, 70-82; male, 33%) from 1992 to 2004 who had CNS lymphoma that involved the brain, the eyes, or both, who were treated with high-dose methotrexate as initial therapy (3.5-8.0 g/m²).

Medical records for these patients indicated that they displayed a median Karnofsky performance status of 80. Elevated levels of lactate dehydrogenase and cerebrospinal fluid protein were found in 45% and 60%, respectively. The locations of the CNS lymphoma were mainly in deep structures (63%), and 15% showed ocular involvement.

Treatment was administered as a 4-hour IV infusion that was followed 24 hours later by oral leucovorin rescue until the plasma methotrexate levels reached a minimum of 0.2 mmol/L. A total of 236 cycles of high-dose methotrexate were administered, with a median of 8 cycles/patient.

During the first cycles, 78% of patients required dose reductions due to reduced creatinine clearance, with dose reductions ultimately required in 85% of cycles. Responses to treatment were assessed by contrast-enhanced magnetic resonance imaging.

Radiographic responses were observed in 93% of 26 evaluable patients. This included 62% with complete response and 8% showed progressive disease. The median rates of progression-free survival and overall survival were 7.1 months and 37 months, respectively.

Toxicity that was associated with the high-dose treatment was observed in 78% of patients, according to the National Cancer Institute Common Terminology Criteria for Adverse Events; 11% were grade 3/4 toxicity events. The researchers observed mucositis in 56% of patients (grade 3, 4%; no grade 4), haematological complications in 30% (grade 3/4, 4%), and increased creatinine in 22% (no grade 3/4).

One patient (4%) had a myocardial infarction, and 11% of patients required treatment discontinuation due to these toxicities.

Dr. Zhu stressed that this elderly population of patients with CNS lymphoma showed similar radiographic responses and comparable rates of progression-free survival and overall survival to what has been reported in younger patients with CNS lymphoma.

As this treatment is only associated with toxicities that mainly comprise mild and reversible azotemia and gastrointestinal effects, this suggests that high-dose methotrexate should indeed be considered for all newly diagnosed patients with CNS lymphoma, including the elderly, he concluded.


[Study title: High-Dose Methotrexate for Elderly Patients With Newly Diagnosed Primary Central Nervous System Lymphoma. Abstract 296]

E-Mail this DGDispatch to a colleague

To print, use this version