1. Chemoradiotherapy with temozolomide after high-dose methotrexate for primary CNS lymphoma: a multicenter phase I study of a response-adapted strategy.
- Author
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Chiesa S, Hohaus S, Falcinelli L, D'Alò F, Martelli MF, Manfrida S, Beghella Bartoli F, Colosimo C, Valentini V, Aristei C, and Balducci M
- Subjects
- Adolescent, Adult, Aged, Antimetabolites, Antineoplastic therapeutic use, Antineoplastic Agents, Alkylating adverse effects, Brain Neoplasms drug therapy, Brain Neoplasms pathology, Chemical and Drug Induced Liver Injury etiology, Chemotherapy, Adjuvant, Cognition Disorders chemically induced, Consolidation Chemotherapy, Female, Hematologic Diseases chemically induced, Humans, Kaplan-Meier Estimate, Lymphoma, Non-Hodgkin drug therapy, Lymphoma, Non-Hodgkin pathology, Male, Maximum Tolerated Dose, Methotrexate administration & dosage, Methotrexate therapeutic use, Middle Aged, Neoplasm, Residual, Progression-Free Survival, Prospective Studies, Temozolomide adverse effects, Young Adult, Antineoplastic Agents, Alkylating therapeutic use, Brain Neoplasms therapy, Chemoradiotherapy, Cranial Irradiation, Lymphoma, Non-Hodgkin therapy, Temozolomide therapeutic use
- 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/m
2 ) 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.- Published
- 2020
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