Pituitary tumors are mostly benign lesions, although 5-35% are locally invasive. A small number exhibit a more aggressive course, infiltrating dura, bone and sinuses, and are designated highly aggressive. However, the presence of
metastases separate from the pituitary in the central nervous system or at a distance is necessary to designate
pituitary tumors as
carcinomas, i.e. truly malignant. When conventional therapeutic modalities fail, systemic
chemotherapy remains the last option. We report seven such patients, three with highly aggressive and four with malignant
pituitary tumors (n=4) four women; median age, 32 yr; range, 23-48 yr), who received one or more courses of
chemotherapy with
lomustine and
5-fluorouracil (median, two courses; range, one to six courses). Three patients with systemic metastatic disease had a shorter survival (median, 5 months; range, 1-14 months) than the one patient with central nervous system
metastases alone (10 yr). A patient with an aggressive nonmetastatic
prolactinoma who initially responded to
chemotherapy died from another nondisease-associated cause. Two patients, one with an aggressive and one with a metastatic
tumor, achieved symptomatic improvement with a median duration of 6 months. A hormonal reduction greater than 50% was observed in two of seven patients; only one patient who had an aggressive
tumor obtained an objective
tumor response. The median survival from the time of initiation of
chemotherapy in patients with malignant
tumors ranged from 3-65 months. Two patients with malignant
tumors developed
disease progression while receiving
chemotherapy; no patient with extracranial
metastases showed a response. Treatment was well tolerated, with minimal individual side-effects. Three patients with no response to initial treatment received different chemotherapeutic regimens with no additional response. All patients with metastatic malignant
tumors eventually died. Treatment with cytotoxic
chemotherapy is noncurative, and current experience is limited. Until another more specific form of treatment is available,
chemotherapy may still be of some value in patients with highly aggressive and malignant
pituitary tumors, at least in achieving a temporary remission or delay in progression. The combination of
lomustine/
5-fluorouracil proved easy to administer with minimal toxicity, although the response rate was only 14%. Until a more specific treatment is found, an optimal chemotherapeutic regimen needs to be established.