Hyperprolactinemia and hypothyroidism following cytotoxic therapy for central nervous system malignancies.

Endocrinologic dysfunction including hyperprolactinemia and hypothyroidism are recognized complications of irradiation to the hypothalamic-pituitary axis or thyroid gland in the course of treating CNS malignancies. However, the frequency of these adverse effects in both short- and long-term survivors may be underestimated. Sixty-five patients treated in the University of Rochester Cancer Center since 1968 with radiation with or without BCNU chemotherapy for CNS tumors not involving the hypothalamic-pituitary axis were evaluated for thyroid, prolactin, and gonadal disturbances regardless of clinical symptomatology. Prolactin values were elevated in 19 of 47 patients (40%). For males and females treated with greater than 55 Gy, abnormal values were present in nine of 11 (82%) and seven of 14 (50%), respectively. For males and females treated with less than or equal to 55 Gy, two of nine (22%) and one of 13 (8%), respectively, were abnormal (P = .0001). Six of six patients who also received BCNU chemotherapy were hyperprolactinemic, as compared with six of ten (60%) who did not receive BCNU. Seven of eight females with elevated prolactin levels had menstruation abnormalities, and five of seven adult males noted a decrease in libido. Mild abnormalities in testosterone concentration were found in three of nine men evaluated, all of whom had normal gonadotropins. Of 47 patients who did not receive irradiation to the spinal axis (and thus the thyroid gland), ten (21%) had a decreased thyroxin (T4) value. Only one of these patients had an elevated thyroid-stimulating hormone (TSH) value. Of 32 patients who received greater than 55 Gy, ten (31%) had a low T4, compared with zero of 15 who received less than or equal to 55 Gy (P = .0001). Four of eight patients (50%) who also received BCNU had low T4 values, as compared with three of 14 (21%) who did not receive BCNU. Of 15 patients who were treated with 4 to 10 MV photon irradiation to the spinal axis, five patients (33%) had elevated TSH values. The mean spinal axis dose in these patients was 33 Gy. Two euthyroid children in this group manifested the early onset of puberty. The complex of endocrinologic abnormalities observed in several patients receiving only cranial irradiation, that is elevated prolactin, decreased thyroid, and gonadal hormone secretion in the presence of otherwise normal pituitary hormone levels, suggests a radiation-induced insult to the hypothalamic regulation of pituitary function.

Simultaneous radiation therapy and cisplatin chemotherapy in advanced cancer of the head and neck. A pilot study at Tygerberg Hospital, Parowvallei, South Africa.

Fifty patients with advanced carcinoma of the head and neck were treated in a nonrandomized pilot study utilizing simultaneous cisplatin and radiotherapy. Treatment was delivered in two segments. The initial partial course (PC) consisted of 75-100 mg/m2 of cisplatin and concomitant radio-therapy to 20.00 Gy in 1 week, with 4-week split. Patients who tolerated therapy and experienced at least a partial response (PR) went on to complete the full course of therapy (FC), with the second phase consisting of 120 mg/m2 of cisplatin and 38.40 Gy of radiation. Total cisplatin delivered ranged between 195 and 220 mg/m2, and the total radiation dose was 58.40 Gy. Of 38 evaluable patients, 31 (82%) had at least a partial response (PR). However, at time of analysis 20 months after study, 27 (71%) patients were alive with disease or dead. Mean disease-free survival (DFS) for patients receiving FC therapy (10.05 months) was greater than that for patients who received only PC therapy (2.65 months), but the difference in overall survival (OS) was not statistically significant (11.95 FC versus 10.29 PC). Response rates and the minimal toxicity are within the range of other reported studies. Randomized studies should seek optimal time-dose schedule and establish advantages in terms of crude survival and disease-free survival.