title: Failure of temozolomide and conventional doses of pegvisomant to attain biochemical control in a severe case of acromegaly.
abstract: It has been suggested that treatment with adequate dose titration of pegvisomant, a GH antagonist, up to a maximum of 40 mg daily, can achieve IGF-1 normalisation in virtually all patients with acromegaly. On the other hand, temozolomide (TMZ), an alkylating cytostatic agent, has been reported to reduce pituitary tumour size and hormone hypersecretion in a small number of aggressive pituitary macroadenomas. In this paper we report the case of a patient resistant to very high doses of pegvisomant used in combination with somatostatin analogs (SSA) and to TMZ therapy. The patient, initially a 22 year-old man with an invasive GH-secreting pituitary macroadenoma (IGF-1, 371% upper limit of normal), had active acromegaly despite a repeat transsphenoidal surgery followed by radiotherapy and SSA (octreotide 800 μg sc daily) (IGF-1, 262% ULN). In combination with SSA, pegvisomant was started at 20 mg daily and doses were titrated up to 60 mg daily. IGF-1 was moderately reduced and stabilized at 200% ULN after 1 year of treatment. Serum pegvisomant level was 30,500 ng/l, the denaturalized GHBP concentration 1,120 pM and the endogenous GH level was 220 μg/l. Pegvisomant was stopped and TMZ therapy was given for 5 cycles. However, the patient reported an increase of acromegaly symptoms and the serum IGF-1 was raised to the same level prior to pegvisomant therapy. Consequently, pegvisomant was tried again with doses up to 100 mg daily finally resulting in normalisation of serum IGF-1 level and improvement of acromegaly symptoms and patient well-being. We conclude that in some patients with severe acromegaly refractory to multimodal therapy, biochemical control may be difficult to attain with conventional doses of pegvisomant or TMZ therapy.
authors.affiliation: Department of Endocrinolgy, CHUM Research Centre, Notre-Dame Hospital, 1560, rue Sherbrooke East, Montreal, QC, H2L 4M1, Canada.
authors.forename: Emilie
authors.initials: E
authors.lastname: Morin
authors.forename: France
authors.initials: F
authors.lastname: Berthelet
authors.forename: John
authors.initials: J
authors.lastname: Weisnagel
authors.forename: Martin
authors.initials: M
authors.lastname: Bidlingmaier
authors.forename: Omar
authors.initials: O
authors.lastname: Serri
mesh_terms: D000172:Acromegaly / Q000188:drug therapy*; D000328:Adult; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019382:Human Growth Hormone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D000077204:Temozolomide; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D019382:Human Growth Hormone; D003606:Dacarbazine; C406545:pegvisomant; D000077204:Temozolomide
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