A phase I dose escalation study using simultaneous integrated-boost IMRT with temozolomide in patients with unifocal glioblastoma.
OBJECTIVE
To evaluate the maximum tolerated dose of simultaneous integrated-boost intensity-modulated radiotherapy (SIB-IMRT) associated with temozolomide in patients with glioblastoma.


METHODS
Between November 2009 and January 2012, nine patients with malignant glioma were enrolled in this phase I clinical trial. Radiotherapy was delivered using fractions of 2.5Gy on the planning target volume b and of 1.9Gy on the planning target volume a. Volumes were defined as follow: gross tumour volume b: tumour taking up contrast on T1 weighted MRI images; clinical target volume b: gross tumour volume b+0.5cm (adapted to the anatomical structures) and lastly planning target volume b: clinical target volume b+0.5cm; gross tumour volume a: tumour (gross tumour volume b)+2cm and including oedema outlined on T2Flair MRI sequences; clinical target volume a gross tumour volume a+0.5cm (adapted to the anatomical structures); planning target volume a: clinical target volume a+0.5cm. Three patients were enrolled at each of the three levels of dose (70, 75 and 80Gy prescribed on the planning target volume b and 56, 60 and 60.8Gy on the planning target volume a). Radiotherapy was delivered with temozolomide according to the standard protocol. Dose-limiting toxicities were defined as any haematological toxicities at least grade 4 or as any radiotherapy-related non-haematological acute toxicities at least grade 3, according to the Common Terminology Criteria for Adverse Events, version 3.0.


RESULTS
Until the last dose level of 80Gy, no patient showed dose-limiting toxicity.


CONCLUSIONS
SIB-IMRT, at least until a dose of 80Gy in 32 daily fractions, associated with temozolomide is feasible and well tolerated.
Radiotherapy Department, centre Georges-François-Leclerc, 1, rue du Pr-Marion, 21079 Dijon, France. Electronic address: gtruc@cgfl.fr.
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Truc
Radiotherapy Department, institut de cancérologie de Lorraine, avenue de Bourgogne, 54500 Vandœuvre-lès-Nancy, France.
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Bernier
Radiotherapy Department, centre Georges-François-Leclerc, 1, rue du Pr-Marion, 21079 Dijon, France.
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Mirjolet
Biostatistics and Epidemiological Unit, centre Georges-François-Leclerc, 1, rue du Pr-Marion, 21079 Dijon, France.
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Dalban
Radiation Physics Department, centre Georges-François-Leclerc, 1, rue du Pr-Marion, 21079 Dijon, France.
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Mazoyer
Methodology and Quality of Life in Oncology unit (EA 3181), CHU de Besançon, 25000 Besançon, France.
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Bonnetain
Radiotherapy Department, hôpital privé les Dentellières, 10, avenue Vauban, 59300 Valenciennes, France.
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Blanchard
Radiotherapy Department, hôpital privé Drevon, 7, rue des Princes-de-Condé, 21000 Dijon, France.
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Lagneau
Radiotherapy Department, centre Georges-François-Leclerc, 1, rue du Pr-Marion, 21079 Dijon, France.
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Maingon
Radiotherapy Department, centre Paul-Strauss, 3, rue de la Porte-de-l'Hôpital, 67000 Strasbourg, France.
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Noël
D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000009:adverse effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D011879:Radiotherapy Dosage; D050397:Radiotherapy, Intensity-Modulated; D000077204:Temozolomide
D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide
Dose escalation; Escalade de dose; Essai clinique de phase I; Glioblastoma; Glioblastome; Phase I clinical trial; SIB-IMRT