A phase II trial of intra-cerebrospinal fluid alpha interferon in the treatment of neoplastic meningitis.
BACKGROUND
Neoplastic meningitis (NM), a metastatic complication of both primary central nervous system and systemic cancer, occurs in 1-5% of patients with known cancer. Currently available treatment options are limited and provide only modest benefit. The current study was performed to determine the toxicity and response rate of intra-cerebrospinal fluid (CSF) alpha interferon (alpha-IFN) in the treatment of patients with NM.


METHODS
Twenty two patients (median age, 56 years) with clinical and cytologically documented NM received intra-CSF alpha-IFN. Tumor histologies included: lung (five patients); brain (five patients); non-Hodgkin lymphoma (three patients); breast (three patients); melanoma (two patients); chronic myelogenous leukemia (two patients); colon (one patient); and prostate (one patient). Concurrent involved-field radiotherapy (12 out of 22 patients) or systemic chemotherapy (11 out of 22) was administered based on clinical indications. -alpha-IFN was administered at a fixed dose (1 x 10(6) IU every other day given three times per week for four weeks by induction). Patients were evaluated by CSF cytology and neurologic examination at the conclusion of induction therapy. Responding patients continued to receive alpha-IFN with monthly evaluations.


RESULTS
Ten out of 22 patients (45%) treated with alpha-IFN had a cytologic response and either stable or improved neurologic status at the conclusion of induction. Duration of response ranged from 8 to 40 weeks (median, 16 weeks). Toxicity was manifested as transient chemical arachnoiditis (16 out of 22 patients; 60% of all treatment cycles) and chronic fatigue (20 out of 22 patients). No treatment-related hospitalizations or deaths were seen.


CONCLUSIONS
alpha-IFN has modest activity against NM. However, it is associated with considerable toxicity at the dose and schedule used in the current study and, as a result, may prove difficult to administer.
Chamberlain
Marc C
MC
Department of Neurology, University of Southern California/Norris Cancer Center, 1441 Eastlake Ave., Suite 3459, Los Angeles, CA 90033-0804, USA. chamberl@usc.edu
D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000150:complications / Q000556:secondary; D003110:Colonic Neoplasms / Q000150:complications; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000150:complications; D008175:Lung Neoplasms / Q000150:complications; D008228:Lymphoma, Non-Hodgkin / Q000150:complications; D008297:Male; D008545:Melanoma / Q000150:complications; D008581:Meningitis / Q000134:cerebrospinal fluid / Q000209:etiology / Q000628:therapy*; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications*; D011471:Prostatic Neoplasms / Q000150:complications; D011994:Recombinant Proteins; D016896:Treatment Outcome
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins