Combined therapy with somatostatin analogues and weekly pegvisomant in active acromegaly

Feenstra, J.; Herder, WW de; Have, Smth ten; Beld, AW van den; Feelders, RA; Janssen, Joseph A M J L; Lely, AJ van der

doi:10.1016/s0140-6736(05)63011-5

Cited by 216 publications

(153 citation statements)

References 6 publications

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“…However, since a remarkable 83% of those acromegalic patients treated with pegvisomant in this country are monitored and documented in this German Database, one strength of the study is the nationwide reflection of clinical practice under field conditions, which frequently differ from clinical studies. Over the years between 2004 and 2008, an increasing use of combination therapies was recognized (14,15). Another strength of this observational study was the careful observation of side effects.…”

Section: Discussionmentioning

confidence: 99%

The German ACROSTUDY: past and present

Buchfelder

Schlaffer²,

Droste³

et al. 2009

European Journal of Endocrinology

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Pivotal studies have demonstrated that pharmacotherapy with pegvisomant (Somavert) is a highly effective treatment for acromegaly. Since clinical experience with the drug was very limited, the Pegvisomant Observational Study was launched in Germany immediately with the drug becoming commercially available to patients early in 2004. Its purpose was to record safety and efficacy data on as many patients as possible.As of 12th August 2008 a total of 371 patients (185 males, 186 females) had been included in the study. They were on pegvisomant therapy for an average of 118 weeks. Median and mean doses of pegvisomant were 15 and 16.4 mg/day respectively. Treatment efficacy was monitored by IGF1 levels and the patients symptoms were evaluated by completion of a questionnaire (patient-assessed acromegaly symptom questionnaire). Safety data included liver function tests, fasting glucose, HbA1c measurements, and tumor size monitoring by repeated magnetic resonance imaging.Normalization of IGF1 ranged from 55.7% of the 273 patients assessed after 6 months to 71.3% of 202 patients assessed after 24 months of treatment. It was 70.7% after 36 months (133 patients), 64.8% at 48 months (71 patients), and 58.4% after 60 months (24 patients). In 39 patients (10.9%) treatment was discontinued due to serious adverse events or adverse events with 25 (6.7%) of these patients having a potential causal relationship with the pegvisomant treatment. Liver function tests became abnormal in 20 patients and another three patients were recorded to have hepatobiliary disorders. Tumor size increase was reported in 20 patients, but only confirmed in nine patients by careful revision of all available images. Local injection site reactions were observed in 12 patients.In conclusion, in this large group of pegvisomant-treated patients, long-term data for up to 5 years of treatment are now available. In 71.3% of patients with previously not sufficiently treatable acromegaly, IGF1 levels were normalized by pegvisomant therapy. Elevated transaminases usually normalized after discontinuation but in half of the affected patients also despite continuation of treatment without dose alteration. Tumor progression was a rare event. It did not exceed the expected rate in patients with acromegaly not treated with pegvisomant. As from this presently largest database of acromegalic patients treated with pegvisomant, long-term results are encouraging. The German data are now merged into the global ACROSTUDY and will constitute a major portion of the international ACROSTUDY project as a continuing global web-based observational study.

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Section: Discussionmentioning

confidence: 99%

The German ACROSTUDY: past and present

Buchfelder

Schlaffer²,

Droste³

et al. 2009

European Journal of Endocrinology

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“…Furthermore, the addition of weekly pegV at doses of up to 160 mg/week in patients with acromegaly uncontrolled on maximum dose of somatostatin analogues alone was effective at normalizing IGF1 in all 32 patients (6,7).…”

Section: Introductionmentioning

confidence: 93%

Successful use of weekly pegvisomant administration in patients with acromegaly

Higham

Thomas²,

Bidlingmaier³

et al. 2009

European Journal of Endocrinology

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Context: Clinical trials using 80 mg once weekly pegvisomant (pegV) in active acromegaly led to a 30% fall in serum IGF1. Subsequent studies demonstrated that daily administration of up to 40 mg/day achieved an IGF1 within reference range in 97% of patients. PegV has a half-life of O70 h suggesting weekly dosing may be possible but using higher doses than in the initial trials. Objective: To determine the efficacy of weekly dosing of pegV. Design: A two center, open-label prospective study in patients with acromegaly converted from a stable daily dose of pegV (median dose 15 mg daily (range 10-20 mg od), IGF1 normal for 3 months prior to inclusion) to twice-weekly (week 0-16) followed by once-weekly (week 16-32) administration. Results: Seven patients (4M, age 57G7 years, 6/7 prior transsphenoidal surgery, 7/7 prior radiotherapy) were recruited. Six patients completed the twice-weekly and five patients both the twice-weekly and once-weekly administration. Headaches led to two patient withdrawals at 0C24 weeks. Mean pre-dose serum IGF1 levels remained stable with the different administration regimens (IGF1 baseline 145G39 ng/ml, twice-weekly 124G39 ng/ml and once-weekly 127G22 ng/ml) and all values were within age adjusted IGF1 reference range. PegV dose was reduced in two patients and five opted to continue weekly administration at trial termination. Safety and quality of life parameters remained stable. Conclusions: Twice and once-weekly administration of pegV is effective in controlling serum IGF1 levels in acromegaly and although not formally assessed, continuation of weekly dosing in five patients at study conclusion suggests patient preference for this regimen.

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“…with GH receptor blockade: a study of the long-term efficacy and safety of combination therapy (long-acting somatostatin analog plus twice weekly pegvisomant) reported that IGF-1 levels normalized for all 32 patients; however, transient elevation in liver enzymes was observed in eleven patients, with a higher risk for patients diagnosed with diabetes mellitus [79]. There is limited data on pegvisomant treatment in children, mostly case studies, which report successful outcomes [80,81].…”

Section: Pituitary Adenomasmentioning

confidence: 99%

Pituitary tumors in childhood: update of diagnosis, treatment and molecular genetics

Keil

Stratakis

2008

Expert Review of Neurotherapeutics

122

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Pituitary tumors are rare in childhood and adolescence, with a reported prevalence of up to 1 per million children. Only 2 -6% of surgically treated pituitary tumors occur in children. Although pituitary tumors in children are almost never malignant and hormonal secretion is rare, these tumors may result in significant morbidity. Tumors within the pituitary fossa are of two types mainly, craniopharyngiomas and adenomas; craniopharyngiomas cause symptoms by compressing normal pituitary, causing hormonal deficiencies and producing mass effects on surrounding tissues and the brain; adenomas produce a variety of hormonal conditions such as hyperprolactinemia, Cushing disease and acromegaly or gigantism. Little is known about the genetic causes of sporadic lesions, which comprise the majority of pituitary tumors, but in children, more frequently than in adults, pituitary tumors may be a manifestation of genetic conditions such as multiple endocrine neoplasia type 1 (MEN 1), Carney complex, familial isolated pituitary adenoma (FIPA), and McCune-Albright syndrome. The study of pituitary tumorigenesis in the context of these genetic syndromes has advanced our knowledge of the molecular basis of pituitary tumors and may lead to new therapeutic developments.

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Combined therapy with somatostatin analogues and weekly pegvisomant in active acromegaly

Cited by 216 publications

References 6 publications

The German ACROSTUDY: past and present

The German ACROSTUDY: past and present

Successful use of weekly pegvisomant administration in patients with acromegaly

Pituitary tumors in childhood: update of diagnosis, treatment and molecular genetics

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