11 research outputs found
Adjuvant mitotane treatment for adrenocortical carcinoma
Background
Adrenocortical carcinoma is a rare neoplasm characterized by a high risk of recurrence after radical resection. Whether the use of mitotane is beneficial as an adjuvant treatment has been controversial. Our aim was to evaluate the efficacy of adjuvant
mitotane in prolonging recurrence-free survival.
Methods
We performed a retrospective analysis involving 177 patients with adrenocortical cancer who had undergone radical surgery at 8 centers in Italy and 47 centers in Germany between 1985 and 2005. Adjuvant mitotane was administered to 47 Italian
patients after radical surgery (mitotane group), whereas 55 Italian patients and 75 German patients (control groups 1 and 2, respectively) did not receive adjuvant treatment after surgery.
Results
Baseline features in the mitotane group and the control group from Italy were similar; the German patients were significantly older (P = 0.03) and had more stage I or II adrenocortical carcinomas (P = 0.02) than did patients in the mitotane group. Recurrence-free survival was significantly prolonged in the mitotane group, as compared with the two control groups (median recurrence-free survival, 42 months, as compared
with 10 months in control group 1 and 25 months in control group 2; hazard ratios for recurrence, 2.91 (95% confidence interval [CI], 1.77 to 4.78; P<0.001) and 1.97 (95% CI, 1.21 to 3.20; P = 0.005), respectively. Multivariate analysis indicated that mitotane
treatment had a significant advantage for recurrence-free survival. Adverse events associated with mitotane were mainly of grade 1 or 2, but temporary dose reduction was needed in 13% of patients.
Conclusions
Adjuvant mitotane may prolong recurrence-free survival in patients with radically resected adrenocortical carcinoma
Adjuvant mitotane treatment for adrenocortical carcinoma.
Background
Adrenocortical carcinoma is a rare neoplasm characterized by a high risk of recurrence
after radical resection. Whether the use of mitotane is beneficial as an adjuvant
treatment has been controversial. Our aim was to evaluate the efficacy of adjuvant
mitotane in prolonging recurrence-free survival.
Methods
We performed a retrospective analysis involving 177 patients with adrenocortical
cancer who had undergone radical surgery at 8 centers in Italy and 47 centers in
Germany between 1985 and 2005. Adjuvant mitotane was administered to 47 Italian
patients after radical surgery (mitotane group), whereas 55 Italian patients and 75 German
patients (control groups 1 and 2, respectively) did not receive adjuvant treatment
after surgery.
Results
Baseline features in the mitotane group and the control group from Italy were similar;
the German patients were significantly older (P = 0.03) and had more stage I or II
adrenocortical carcinomas (P = 0.02) than did patients in the mitotane group. Recurrence-
free survival was significantly prolonged in the mitotane group, as compared
with the two control groups (median recurrence-free survival, 42 months, as compared
with 10 months in control group 1 and 25 months in control group 2). Hazard
ratios for recurrence were 2.91 (95% confidence interval [CI], 1.77 to 4.78; P<0.001) and
1.97 (95% CI, 1.21 to 3.20; P = 0.005), respectively. Multivariate analysis indicated that
mitotane treatment had a significant advantage for recurrence-free survival. Adverse
events associated with mitotane were mainly of grade 1 or 2, but temporary dose reduction
was needed in 13% of patients.
Conclusions
Adjuvant mitotane may prolong recurrence-free survival in patients with radically resected
adrenocortical carcinoma
Germline NF1 mutational spectra and loss-of-heterozygosity analyses in patients with pheochromocytoma and neurofibromatosis type 1
BACKGROUND: Neurofibromatosis type 1 (NF1) is a pheochromocytoma-associated syndrome. Because of the low prevalence of pheochromocytoma in NF1, we ascertained subjects by pheochromocytoma that also had NF1 in the hope of describing the germline NF1 mutational spectra of NF1-related pheochromocytoma. MATERIALS AND METHODS: An international registry for NF1-pheochromocytomas was established. Mutation scanning was performed using denaturing HPLC for intragenic variation and quantitative PCR for large deletions. Loss-of-heterozygosity analysis using markers in and around NF1 was performed. RESULTS: There were 37 eligible subjects (ages 14-70 yr). Of 21 patients with corresponding tumor available, 67% showed somatic loss of the nonmutated allele at the NF1 locus vs. 0 of 12 sporadic tumors (P = 0.0002). Overall, 86% of the 37 patients had exonic or splice site mutations, 14% large deletions or duplications; 79% of the mutations are novel. The cysteine-serine rich domain (CSR) was affected in 35% but the RAS GTPase activating protein domain (RGD) in only 13%. There did not appear to be an association between any clinical features, particularly pheochromocytoma presentation and severity, and NF1 mutation genotype. CONCLUSIONS: The germline NF1 mutational spectra comprise intragenic mutations and deletions in individuals with pheochromocytoma and NF1. NF1 mutations tended to cluster in the CSR over the RAS-GAP domain, suggesting that CSR plays a more prominent role in individuals with NF1-pheochromocytoma than in NF1 individuals without this tumor. Loss-of-heterozygosity of NF1 markers in NF1-related pheochromocytoma was significantly more frequent than in sporadic pheochromocytoma, providing further molecular evidence that pheochromocytoma is a true component of NF1