Temozolomide for aggressive ACTH pituitary tumors: failure of a second course of treatment

Campderá, M.; Palacios, Nuria; Aller, Javier; Magallón, Rosa; Martín, Paloma; Saucedo, Gertrudis; Lilienfeld, Howard; Estrada, Javier

doi:10.1007/s11102-015-0694-x

Cited by 32 publications

(13 citation statements)

References 31 publications

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“…The treatment duration was significantly shorter in nonresponders, showing a likely influence of early evaluation and clinician's choice in the decision to stop treatment, more than side effects (only one treatment cessation was due to side effects). As already suggested in the literature (15,30), all anew treatment attempts with TMZ in cases of relapse failed, as did all salvage therapies. Therapeutic resources in such cases are therefore limited.…”

Section: Discussionmentioning

confidence: 66%

Temozolomide treatment can improve overall survival in aggressive pituitary tumors and pituitary carcinomas

Lasolle

Cortet

Castinetti

et al. 2017

European Journal of Endocrinology

118

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Objectives Only few retrospective studies have reported an efficacy rate of temozolomide (TMZ) in pituitary tumors (PT), all around 50%. However, the long-term survival of treated patients is rarely evaluated. We therefore aimed to describe the use of TMZ on PT in clinical practice and evaluate the long-term survival. Design Multicenter retrospective study by members of the French Society of Endocrinology. Methods Forty-three patients (14 women) treated with TMZ between 2006 and 2016 were included. Most tumors were corticotroph (n = 23) or lactotroph (n = 13), and 14 were carcinomas. Clinical/pathological characteristics of PT, as well as data from treatment evaluation and from the last follow-up were recorded. A partial response was considered as a decrease in the maximal tumor diameter by more than 30% and/or in the hormonal rate by more than 50% at the end of treatment. Results The median treatment duration was 6.5 cycles (range 2–24), using a standard regimen for most and combined radiotherapy for six. Twenty-two patients (51.2%) were considered as responders. Silent tumor at diagnosis was associated with a poor response. The median follow-up after the end of treatment was 16 months (0–72). Overall survival was significantly higher among responders (P = 0.002); however, ten patients relapsed 5 months (0–57) after the end of TMZ treatment, five in whom TMZ was reinitiated without success. Discussion Patients in our series showed a 51.2% response rate to TMZ, with an improved survival among responders despite frequent relapses. Our study highlights the high variability and lack of standardization of treatment protocols.

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Section: Discussionmentioning

confidence: 66%

Temozolomide treatment can improve overall survival in aggressive pituitary tumors and pituitary carcinomas

Lasolle

Cortet

Castinetti

et al. 2017

European Journal of Endocrinology

118

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“…In other published pituitary tumour cases, haemorrhage into cerebral metastases has been reported as a complication of severe thrombocytopaenia (114). A case of liver toxicity complicating ketoconazole therapy when TMZ was introduced was reported (115). In the wider literature, rare cases of hypersensitivity pneumonitis (116), Stevens-Johnson syndrome (117) and cholestatic hepatitis (118) have been described.…”

Section: Reasoningmentioning

confidence: 99%

“…In total, 16 patients in 6 studies have been reported (11,12,25,115,134) (unpublished ESE survey). In 15 patients, TMZ was given as monotherapy, in one patient (134) in combination with other drugs.…”

Section: Second Attempt With Tmz ± Combinationsmentioning

confidence: 99%

European Society of Endocrinology Clinical Practice Guidelines for the management of aggressive pituitary tumours and carcinomas

Raverot

Burman

McCormack

et al. 2018

European Journal of Endocrinology

482

583

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Background: Pituitary tumours are common and easily treated by surgery or medical treatment in most cases. However, a small subset of pituitary tumours does not respond to standard medical treatment and presents with multiple local recurrences (aggressive pituitary tumours) and in rare occasion with metastases (pituitary carcinoma). The present European Society of Endocrinology (ESE) guideline aims to provide clinical guidance on diagnosis, treatment and follow-up in aggressive pituitary tumours and carcinomas. Methods: We decided upfront, while acknowledging that literature on aggressive pituitary tumours and carcinomas is scarce, to systematically review the literature according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. The review focused primarily on first-and second-line treatment in aggressive pituitary tumours and carcinomas. We included 14 single-arm cohort studies (total number of patients = 116) most on temozolomide treatment (n = 11 studies, total number of patients = 106). A positive treatment effect was seen in 47% (95% CI: 36-58%) of temozolomide treated. Data from the recently performed ESE survey on aggressive pituitary tumours and carcinomas (165 patients) were also used as backbone for the guideline. In patients responding to first-line temozolomide, we suggest continuing treatment for at least 6 months in total. Furthermore, the guideline offers recommendations for patients who recurred after temozolomide treatment, for those who did not respond to temozolomide and for patients with systemic metastasis.

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“…We also noticed that there are 3 cases that received reduction in tumor size after first course of temozolomide therapy but failed in second course of treatment when disease progressed. [ 16 ]…”

Section: Discussionmentioning

confidence: 99%

Treatment of aggressive prolactinoma with temozolomide

et al. 2017

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Rationale:Aggressive pituitary adenomas and pituitary carcinomas are rare and demand multiple treatment strategies. Temozolomide, an orally active alkylating chemotherapeutic agent, has recently been recommended as a salvage medication for refractory pituitary adenomas or carcinomas.Patient concerns:A 17-year-old male presenting with aggressive prolactinoma that continued to progress despite surgery, gamma knife, and dopamine agonists.Diagnoses:The diagnosis of refractory aggressive prolactinoma was made on the basis of clinical findings and the lack of efficacy of conventional treatment.Interventions:The patient received the most frequently recommended regimen of temozolomide treatment for 22 cycles.Outcomes:Temozolomide resulted in a remarkable shrinkage of tumor mass and inhibition of prolactin secretion and this patient's clinical condition improved progressively.Lessons:Temozolomide can be used as a salvage treatment to refractory pituitary tumors and o(6)-methylguanine-DNA methyltransferase (MGMT) status is a significant predictor to the effectiveness of temozolomide based on the existing literature.

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Temozolomide for aggressive ACTH pituitary tumors: failure of a second course of treatment

Abstract: The treatment with TMZ is effective and safe in patients with aggressive corticotrophin tumors resistant to conventional therapy. Nevertheless once the disease progresses, a second course of treatment does not seem to be effective.

Cited by 32 publications

References 31 publications

Temozolomide treatment can improve overall survival in aggressive pituitary tumors and pituitary carcinomas

Temozolomide treatment can improve overall survival in aggressive pituitary tumors and pituitary carcinomas

European Society of Endocrinology Clinical Practice Guidelines for the management of aggressive pituitary tumours and carcinomas

Treatment of aggressive prolactinoma with temozolomide

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