Abstract

Abstract 3695

Poster Board III-631

Introduction

This study was performed to determine the maximum-tolerated dose (MTD) of oral idarubicin in combination with oral cyclophosphamide (CY), etoposide (ET), prednisolone (PRED) and intravenous (IV) rituximab (RI) administrated to previously untreated patients (pts) (60-80 years-old) with high grade stage III or IV non Hodgkin lymphoma. Secondary objectives were evaluation of toxicity and efficacy.

Patients and Methods

Idarubicin was administrated per os on day 1 with doses starting at 20 mg/m2 and escalated by 10 mg/m2 increments. Each idarubicin dose level included 3 to 6 pts. No intrapatient dose escalatation was allowed. Dose-limiting toxicity (DLT) was defined as grade 4 neutropenia lasting at least 4 days or grade 4 thrombopenia or more than grade 2 extra haematological toxicity. The MTD was defined as the dose level at which at least 2 of 3 or 3 of 6 pts experienced a DLT. CY and ET were given per os on day 1 to 3 at the fixed dose of 150 mg/m2 and 100 mg/m2 respectively. PRED was given at the fixed dose of 50 mg/m2 per os on day 1 to 5. RI was administrated IV on day 1 at the fixed dose of 375 mg/m2. G-CSF was systematically used from day 6 to haematological reconstitution. Eight cycles were planned at 3 week-intervals.

Results

Between October 2003 and August 2008, 19 immunocompetent pts [median age 70 (range 62-80)] with a new diagnosis of high grade non Hodgkin lymphoma received 128 cycles at 3 different idarubicin dose levels. No DLT was observed at dose level 1 (20 mg/m2), whereas 2 of 6 patients developed a DLT at dose level 2 (30 mg/m2). All 3 pts developed a DLT at level 3 (40 mg/m2) which was considered as MTD. Seven pts were enrolled at level 2 to confirm the results. Main toxicity results are summarized in the table below. No toxicity related mortality was observed. Two pts stopped treatment because of toxicity and 8 pts received a decreased dose. Overall response rate and complete response rate were 79% and 68% respectively. With a median follow-up of 22 months, the 2-year survival rates were 75% (95% CI: 45-90) for all pts and 58 % (95% CI: 21-83) for dose level 2 pts.

Idarubicin level: Number of cycles at planned dose (89/128) Haemoglobin G1-G2 G3-G4 Platelets <G4 G4<g4 g4<=” td=“”></g4 g4<=“> ANC <G4 G4 Infection G1-G2 G3-G4 
Level 1 (24 cycles) 14 0 12 0 9 4 1 0 
Level 2 (61 cycles) 29 2 9 1 18 11 8 3 
Level 3 (4 cycles) 1 2 2 0 0 4 1 2 
Idarubicin level: Number of cycles at planned dose (89/128) Haemoglobin G1-G2 G3-G4 Platelets <G4 G4<g4 g4<=” td=“”></g4 g4<=“> ANC <G4 G4 Infection G1-G2 G3-G4 
Level 1 (24 cycles) 14 0 12 0 9 4 1 0 
Level 2 (61 cycles) 29 2 9 1 18 11 8 3 
Level 3 (4 cycles) 1 2 2 0 0 4 1 2 
Conclusion

This first analysis clearly shows that the MTD of oral idarubicin administrated with CY, ET, PRED and RI, is 40 mg/ m2 on day 1 every 21-day cycle. The recommended dose study is ongoing. Overall survival data seems to be similar to previous publications. (Coiffier et al, NEJM 2002). Future development of subcutaneous anti-CD20 antibody could represent a special interest for this new oral chemotherapeutic protocol in order to improve the quality of life of elderly pts.

Disclosures:

No relevant conflicts of interest to declare.

Author notes

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Asterisk with author names denotes non-ASH members.