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

Helene Lasolle (1, 2) , Christine Cortet (3, 4) , Frederic Castinetti (5, 6) , Lucie Cloix (7, 8) , Philippe Caron (9, 9) , Brigitte Delemer (10, 10) , Rachel Desailloud (11) , Christel Jublanc (12) , Christine Lebrun-Frenay (13, 14) , Jean-Louis Sadoul (13, 15) , Luc Taillandier (16) , Marie Batisse-Lignier (17, 18) , Fabrice Bonnet (19) , Nathalie Bourcigaux (20) , Damien Bresson (21) , Olivier Chabre (22) , Philippe Chanson (23, 24) , Cyril Garcia (25) , Magalie Haissaguerre (26, 27) , Yves Reznik (28) , Sophie Borot (29, 30) , Chiara Villa (31, 32) , Alexandre Vasiljevic (33) , Stephan Gaillard (31) , Emmanuel Jouanneau (1, 2) , Guillaume Assie (34, 32) , Gerald Raverot (33, 1)

1 UCBL - Université Claude Bernard Lyon 1
2 HCL - Hospices Civils de Lyon
3 Hôpital Claude Huriez [Lille]
4 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
5 TIMONE - Hôpital de la Timone [CHU - APHM]
6 CHU Marseille
7 CHRU Tours - Centre Hospitalier Régional Universitaire de Tours
8 Hôpital Bretonneau
9 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
10 Hôpital universitaire Robert Debré [Reims]
11 CHU Amiens-Picardie
12 CHU Pitié-Salpêtrière [AP-HP]
13 CHU Nice - Centre Hospitalier Universitaire de Nice
14 CHU - Hôpital Pasteur [Nice]
15 Hôpital l'Archet
16 CHU de Poitiers [La Milétrie] - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
17 CHU Clermont-Ferrand
18 CHU Gabriel Montpied [Clermont-Ferrand]
19 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
20 CHU Saint-Antoine [AP-HP]
21 Hôpital Lariboisière-Fernand-Widal [APHP]
22 CHUGA - Centre Hospitalier Universitaire [CHU Grenoble]
23 Hôpital Bicêtre [AP-HP, Le Kremlin-Bicêtre]
24 Signalisation Hormonale, Physiopathologie Endocrinienne et Métabolique
25 HIA Begin - Hôpital d'Instruction des Armées Begin [Saint-Mandé, France]
26 Hôpital Haut-Lévêque [CHU Bordeaux]
27 CHU Bordeaux
28 Service Endocrinologie - Diabétologie [CHU Caen]
29 Service de Diabétologie - Endocrinologie [CHRU Besançon]
30 Hôpital JeanMinjoz
31 Hôpital Foch [Suresnes]
32 IC UM3 (UMR 8104 / U1016) - Institut Cochin
33 GHE - Groupement Hospitalier Lyon-Est
34 Hôpital Cochin [AP-HP]

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.

Domaines: Sciences du Vivant [q-bio]

Helene Lasolle, Christine Cortet, Frederic Castinetti, Lucie Cloix, Philippe Caron, et al.. Temozolomide treatment can improve overall survival in aggressive pituitary tumors and pituitary carcinomas. European Journal of Endocrinology, 2017, 176 (6), pp.769-777. ⟨10.1530/EJE-16-0979⟩. ⟨hal-03555800⟩