Phase I/II Study of Escalating Doses of Idarubicin in Combination with Methotrexate, Vindesine and Prednisolone in Patients with Primary Central Nervous System Lymphoma: Results of the GOELAMS LCP99 Multicenter Trial.

Abstract

2694 Poster Board II-670 Introduction: This study was performed to determine the maximum-tolerated dose (MTD) and the recommended dose (RD) of idarubicin in combination with methotrexate (MTX), vindesine (VDS) and prednisolone (PRED) given to previously untreated patients (pts) (60–70 years-old) with primary central nervous system lymphoma (PCNSL). Patients and Methods: MTX and VDS were respectively given at the fixed dose of 3 g/m2 (6-hour intravenous [IV]) and 3 mg/m2 IV both on day 1. PRED was given at the fixed dose of 60 mg/m2 (IV or per os) on day 1 to 5. Idarubicin was administrated IV on day 1 with doses starting at 12 mg/m2 and escalated by 2 mg/m2 increments until MTD. Treatment was repeated every 3 weeks, three times. G-CSF was used. Intrathecal chemotherapy (MTX 15 mg, cytarabine 40 mg ) was performed on day 1. Subsequent whole brain irradiation (30 Gy + 10 Gy on residual mass) was performed. Limiting toxicity was defined as grade 4 neutropenia for more than 7 days or thrombopenia grade 4 or extra haematological toxicity more than grade 2. Results: Between 2000 and 2005, 35 immunocompetent pts (19 men, 16 women) with a new diagnosis of PCNSL received 87 cycles at four different idarubicin dose levels. At dose level 1 (12 mg/m2) and level 2 (14 mg/m2), only one of six developed a limiting toxicity. About 3 cases, no limiting toxicity was observed at level 3 (16 mg/m2). Three of six developed a limiting toxicity at level 4 (18 mg/m2) which was considered as MTD. Fourteen patients were enrolled at level 3 to confirm the data. At level 3, main haematological toxicities were neutropenia grade 3 (9%) or grade 4 (40%) and main extra haematological toxicities were infectious disease (5 % grade 3 or 4) and renal failure (grade 2: 9%). Median survival time was 385 days (IC95% 136–679).Overall response rate after radiotherapy was 65.7 % (15 CR, 7 PR). Conclusion: Our study suggests that the RD of idarubicin administrated with MTX, VDS and PRED, should be 16 mg/m2 on day 1 every 21-day cycle. Disclosures: Delwail: Innate Pharma: Honoraria.

Methotrexate plus idarubicin improves outcome of patients with primary central nervous system lymphoma

“…Previous studies have exhibited the efficacy of IDA-containing regimens on PCNSL, although one study failed to reveal its significant effect on patients without MTX [ 30 ] and other studies demonstrated promising results using IDA-containing polychemotherapies based on a high-dose of MTX. [ 31 – 34 ] However, it was also recognized that high responses were associated with acute toxicity; thus, improvement of the efficacy-toxicity balance is crucial in the treatment of these patients. The MTX and IDA regimen has been rarely employed to treat PCNSL in literatures and in our current study; thus, we assessed their therapeutic efficacy with acceptable hematological toxicity.…”

“…recommended a 16 mg/m 2 dose of IDA administrated together with MTX. [ 31 ] Unfortunately, this recommendation was not supported by other clinical trials. [ 30 , 35 , 36 ] Thus, in the current study, we used a median IDA dose of 8.5mg/m 2 .…”

HDMTX-based polychemotherapy including intraventricular therapy in elderly patients with primary CNS lymphoma: a single center series

“…Chemotherapy only trials in elderly patients report median OS of 14.3-49.2 months and median PFS of 5.9-19.5 months (for details see Table 4). 4,7,8,11,14,[17][18][19][20][21][22][23][24] Results with the regimen applied in this retrospective study compare favorably with results of other chemotherapy only regimens, regarding the poor clinical condition of this unselected group of consecutive elderly patients referred to this center with a median KPS of 50, and with 13/43 patients with a KPS <50 at first diagnosis. The vast majority of patients referred to our center was able to receive the planned chemotherapy protocol: Of 46 patients, 43 patients received HDMTX-based chemotherapy, and 32 patients completed treatment including ICV therapy.…”

“…Most recent trials draw the line between younger and elderly PCNSL patients at 65 years, 7 , 17 – 19 as was the case in our study, whereas other trials defined “elderly” as patients >60 years of age. 4 , 8 , 11 , 20 – 24 The trial results on patients with a lower age limit of 60 years were nevertheless considered for interpretation of our results.…”