The role of cytotoxic chemotherapy in the management of aggressive and malignant pituitary tumors

Pituitary tumors are mostly benign lesions, although 5-35% are locally inva sive. A small number exhibit a more aggressive course, infiltrating dura, b one and sinuses, and are designated highly aggressive. However, the presenc e of metastases separate from the pituitary in the central nervous system o r at a distance is necessary to designate pituitary tumors as carcinomas, i .e. truly malignant. When conventional therapeutic modalities fail, systemi c chemotherapy remains the last option. We report seven such patients, thre e with highly aggressive and four with malignant pituitary tumors (n = 4) f our women; median age, 32 yr; range, 23-48 yr), who received one or more co urses of chemotherapy with lomustine and 5-fluorouracil (median, two course s; range, one to six courses). Three patients with systemic metastatic dise ase 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 c hemotherapy died from another nondisease-associated cause. Two patients, on e with an aggressive and one with a metastatic tumor, achieved symptomatic improvement with a median duration of 6 months. A hormonal reduction greate r than 50% was observed in two of seven patients; only one patient who had an aggressive tumor obtained an objective tumor response. The median surviv al from the time of initiation of chemotherapy in patients with malignant t umors ranged from 3-65 months. Two patients with malignant tumors developed disease progression while receiving chemotherapy; no patient with extracra nial metastases showed a response. Treatment was well tolerated, with minim al individual side-effects. Three patients with no response to initial trea tment received different chemotherapeutic regimens with no additional respo nse. All patients with metastatic malignant tumors eventually died. Treatment with cytotoxic chemotherapy is noncurative, and current experienc e is limited. Until another more specific form of treatment is available, c hemotherapy may still be of some value in patients with highly aggressive a nd 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 o nly 14%. Until a more specific treatment is found, an optimal chemotherapeu tic regimen needs to be established.