Chemoradiotherapy with temozolomide after high-dose methotrexate for primary CNS lymphoma: a multicenter phase I study o
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ORIGINAL ARTICLE
Chemoradiotherapy with temozolomide after high-dose methotrexate for primary CNS lymphoma: a multicenter phase I study of a response-adapted strategy Silvia Chiesa 1 & Stefan Hohaus 2,3 & Lorenzo Falcinelli 4 & Francesco D’Alò 2,3 & Massimo Fabrizio Martelli 5 & Stefania Manfrida 1 & Francesco Beghella Bartoli 1 & Cesare Colosimo 3,6 & Vincenzo Valentini 1,3 & Cynthia Aristei 4,7 & Mario Balducci 1,3 Received: 13 November 2019 / Accepted: 11 August 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract This study aimed to define the maximum tolerated dose (MTD) of temozolomide (TMZ) concurrent with radiotherapy (RT) after high-dose methotrexate (HD-MTX) for newly diagnosed primary central nervous system lymphoma (PCNSL). Adult patients with PCNSL were treated according to a response-adapted strategy. HD-MTX (3.5 g/m2) was followed by concomitant RT and escalating TMZ (50–60–75 mg/m2/day, 5 days/week). The total radiation dose was modulated according to the patient’s response to HD-MTX. All patients received 30 Gy to the whole brain plus leptomeninges to C2, including the third posterior of the orbital cavity (clinical target volume 2; CTV2), plus 6, 10, or 16 Gy to the primary site, including the residual mass (CTV1), if a complete response (CR), partial response (PR)/stable disease (SD), or progressive disease (PD) was observed, respectively. Acute toxicities were graded according to the RTOG-EORTC criteria. Dose-limiting toxicity (DLT) was defined as grade 4 hematological toxicity or grade 3–4 hepatic toxicity, although 75 mg/m2/day was the maximum dose regardless of DLT. Neurocognitive function was evaluated using the Mini-Mental State Examination. Three patients were enrolled at each TMZ dose level (total = 9 patients). Twelve lesions were treated. Six patients received 2 cycles of HD-MTX, while 3 received only 1 cycle because of hepatic or renal toxicity. All patients completed chemoradiotherapy without interruptions. No DLT events were recorded. TMZ appears to be tolerable at a dose of 75 mg/m2/day when administered concomitantly with radiotherapy and after HD-MTX. Keywords CNS lymphoma . Chemoradiotherapy . Temozolomide . Phase I study
Introduction Primary central nervous system lymphoma (PCNSL) is a rare and aggressive form of non-Hodgkin lymphoma (NHL).
Although new treatment strategies have improved the median survival duration, the prognosis of PCNSL remains dismal [1, 2]. Currently, this type of lymphoma is treated mainly with radiation therapy and chemotherapy, whereas surgery is only
* Francesco Beghella Bartoli [email protected]
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Sezione di Radioterapia Oncologica, Dipartimento di Chirurgia e Scienze Biomedicali, Università degli studi di Perugia, Azienda Ospedaliera di Perugia, Perugia, Italy
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UOC di Radioterapia Oncologica, Dipartimento Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, largo A. Gemelli 1, 00168 Rome, Italy
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Divisione di Ematolo
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