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Teniposide plus cytarabine as intensification therapy and in continuation therapy for advanced nonlymphoblastic
P T Maluf1, V Odone Filho, L M Cristofani
1Department of Pediatric Hematology-Oncology, Instituto da Criança Professor Pedro de Alcantara, São Paulo University Medical School, Brazil.
Insights
This study shows that an intensive chemotherapy protocol, including teniposide (VM-26), significantly improved remission and survival rates in children with nonlymphoblastic lymphomas. The LNH-II-85 protocol led to high complete remission and event-free survival rates.
Area of Science:
- Pediatric Oncology
- Hematology
- Clinical Chemotherapy
Background:
- Nonlymphoblastic lymphomas (NL) in children require effective treatment protocols.
- Previous regimens at the institution showed less favorable outcomes.
Purpose of the Study:
- To evaluate the efficacy of the LNH-II-85 chemotherapy protocol in pediatric nonlymphoblastic lymphomas.
- To assess remission rates, event-free survival, and the impact of an intensified consolidation phase.
Main Methods:
- A uniform treatment protocol (LNH-II-85) was applied to 39 children (ages 2-11) with NL lymphomas.
- The protocol included remission induction, an intensification phase with teniposide (VM-26) and cytarabine (ARA-C), and a continuation phase.
- Central nervous system (CNS) prophylaxis involved intrathecal methotrexate (MTX), ARA-C, and dexamethasone.
Main Results:
- 38 out of 39 patients achieved complete remission.
- 36 patients were event-free survivors by the end of the analysis.
- Two treatment failures were due to secondary malignancies (leukemias).
Conclusions:
- The LNH-II-85 protocol demonstrated significantly better results compared to previous, less intensive regimens.
- The intensified consolidation phase, particularly with VM-26, showed a favorable impact on patient outcomes.
- The study highlights the effectiveness of this intensive approach in treating pediatric nonlymphoblastic lymphomas.
Purpose And Methods:
Thirty-nine consecutive children (age, 2 to 11 years) with nonlymphoblastic (NL) lymphomas were treated uniformly with chemotherapy based on the LNH-II-85 protocol. The protocol consisted of a remission-induction phase that lasted 30 days and started with cyclophosphamide (CTX) 1.2 g/m2 on day 1, followed by vincristine (VCR) 1.5 mg/m2 on days 3, 10, 17, and 24, daunomycin (DAUNO) 60 mg/m2 on days 12 and 13, and prednisone 40 mg/m2/d for 30 days. If a complete remission was achieved, an intensification regimen was given that consisted of eight courses of teniposide (VM-26) 165 mg/m2 plus cytarabine (ARA-C) 300 mg/m2 every 4 days according to bone marrow tolerance. A continuation phase was subsequently started, with alternating courses of thioguanine (6-TG) 300 mg/m2/d for 4 days plus CTX 1.2 g/m2 on day 5; hydroxyurea 2.5 g/m2/d for 4 days plus DAUNO 45 mg/m2 on day 5; VCR 1.5 mg/m2 plus methotrexate (MTX) 120 mg/m2 (24 hours apart); mercaptopurine (6-MP) 500 mg/m2/d for 4 days plus MTX 40 mg/m2; and VM-26 plus ARA-C for 3 courses (4 days apart), by the end of 48 weeks. CNS prophylaxis consisted of intrathecal administration of MTX, ARA-C, and dexamethasone according to age, administered three times during remission induction and every 6 weeks afterwards.
Results:
By the end of the analysis in July 1991, 38 of 39 patients had attained a complete remission and 36 were event-free survivors. Two failures that occurred after completion of therapy were second malignancies (acute lymphocytic leukemia and acute nonlymphocytic leukemia).
Conclusion:
These results are significantly better than those obtained with less intensive former regimens performed in our institution before the availability of VM-26. The favorable impact of an intense consolidation phase with VM-26 is remarkably exemplified by three additional patients not included in this study whose families withdrew them from therapy after the intensification phase, all three of whom have been in remission.