Activity and safety of dose‐adjusted infusional cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy with rituximab in very elderly patients with poor‐prognostic untreated diffuse large B‐cell non‐Hodgkin lymphoma
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Musolino et al reported their experience with a reduced dose regimen designed for “very elderly” patients with high-risk diffuse large B-cell non-Hodgkin lymphomas.1 They treated 23 patients (median age, 77 years), most of whom were diagnosed with an advanced stage of disease and poor prognostic score, with 6 to 8 courses of dose-adjusted infusional cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy with rituximab (DA-POCH-R). This regimen is an anthracycline-based scheme whose dose intensity, compared with the CHOP regimen, is 88% for doxorubicin, 53% for cyclophosphamide, and nearly 90% for vincristine; however, 12 cycles in 9 patients were administered at reduced doses. The overall response rate was 90%, with a complete response rate of 57%; the 3-year overall survival and event-free survival rates were 56% and 54%, respectively. Hematological toxicity was manageable and nonhematological toxicity was negligible. The authors concluded that this regimen was a reasonable alternative for elderly patients who were not considered to be able to tolerate standard treatment with R-CHOP. Although we believe the study is interesting, the authors did not make specific mention of the criteria used for the recruitment of patients and, in particular, they did not mention the comprehensive geriatric assessment (CGA), based on cumulative comorbidities and the ability to perform basic and instrumental daily life activities.2, 5 In our clinical practice, we treat elderly “fit” patients with R-CHOP, and the majority of “unfit” or “frail” patients are treated with the R-VV regimen, which is comprised of rituximab plus oral vinorelbine and etoposide, and which permits appreciable results with acceptable toxicity and the avoidance of hospital admission. In conclusion, we believe that a broader application of CGA could lead to a better selection of patients and, consequently, studies with more comparable results. Alberto Fabbri MD*, Alessandro Gozzetti MD*, Luigi Rigacci MD , * Department of Hematology, University Hospital of Siena, Siena, Italy, Department of Hematology, University Hospital of Florence, Florence, Italy.Keywords:
Regimen
Chemotherapy regimen
A total of 180 children with acute leukemia was randomized to one of two induction regimens: vincristine plus prednisone, or 6-mercaptopurine plus prednisone. Of 170 patients evaluable for induction therapy, a hematologic remission was achieved in 83% (72/87) on vincristine plus prednisone, and in 93% (77/83) on 6-mercaptopurine plus prednisone. When hematologic remission was achieved, patients were randomized to one of three maintenance schedules: 6-mercaptopurine alone, 6-mercaptopurine plus prednisone for 4 weeks every 3 months, or 6-mercaptopurine plus prednisone plus vincristine for 4 weeks every 3 months. The durations of hematologic remission were compared from the achievement of hematologic remission to bone marrow relapse. The survival data were presented as an overview of the effect of this initial therapy on duration of survival. There was no statistical difference between the two induction regimens. The most important finding in the comparison of the three maintenance schedules was that reinforcement of 6-mercaptopurine maintenance therapy with either prednisone or prednisone plus vincristine resulted in significantly longer durations of remission. Vincristine added to prednisone for reinforcement after induction of remission by vincristine plus prednisone did not increase the duration of hematologic remission or survival over prednisone reinforcement alone.
Mercaptopurine
Maintenance therapy
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Fifty-six untreated patients with childhood with acute lymphoblastic leukemia (ALL) were randomized to receive one of three remission induction regimens: vincristine and prednisone (VP), vincristine, prednisone and daunorubicin (VPD), or vincristine, prednisone and adriamycin (VPA). The complete remission rate was similar for all three groups. Although the anthracycline regimens caused somewhat more rapid leukemic cell reduction than the VP only group, this difference was not significant. Labeling index reduction between study days 1 and 5 was significantly greater (p less than 0.001) with an anthracycline than for the VP group, but there was no difference between the two anthracyclines. Granulocytopenia during induction was significantly increased (p less than 0.05) in both the VPD and VPA groups as compared with VP alone. A significantly higher rate of infectious morbidity (p less than 0.01) was associated with the addition of either anthracycline, but to date no significant differences in remission duration or survival have been observed. The addition of anthracyclines to VP for remission induction in childhood ALL has theoretical advantages, but may be undesirable because of increased morbidity.
Daunorubicin
Acute lymphocytic leukemia
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Fifty-six children with refractory acute lymphocytic leukemia (ALL) were assessed for remission-induction responses to VM-26 (250 mg/m2 per week) in combination with prednisone (40 mg/m2 per day) and vincristine (1.5 mg/m2 per week). Each child had been treated intensively with steroids, vincristine, daunorubicin and L-asparaginase. In fact, all patients had failed to respond to previous reinduction therapy with prednisone-vincristine or had relapsed while receiving vincristine. Our intent in this study was to test whether or not addition of VM-26 to prednisone-vincristine would overcome clinical resistance to these established agents. Complete remissions were induced in 17 patients (0.30) over 4 to 6 weeks. Five of these children, all clinically unresponsive to prednisone-vincristine alone, had complete remissions that lasted longer than 1 year; two remain in remission for 2 1/2 years and both are now off therapy. Myelosuppression, the most serious treatment complication, was documented in 20 of 26 evaluable patients. The median time to recovery of normal marrow function was 15 days. These results demonstrate further the potential of VM-26 in combined-drug treatment of refractory ALL. Whether the effectiveness of this combination represents potentiation of prednisone and vincristine activity by VM-26 or some other, as yet unidentified interaction, remains to be determined.
Refractory (planetary science)
Acute lymphocytic leukemia
Daunorubicin
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Abstract Objective —To evaluate the effect of prednisone alone, compared with a combination of prednisone and vincristine, on platelet counts in bleeding dogs with severe primary immune-mediated thrombocytopenia (IMT). Design —Prospective case study. Animals —24 dogs with severe primary IMT. Procedure —All dogs received immunosuppressive doses of prednisone (1.5 to 2 mg/kg [0.7 to 0.9 mg/lb] of body weight, PO, q 12 h). In addition, 12 dogs received a single dose of vincristine (0.02 mg/kg [0.01 mg/lb], IV). Platelet count, transfusion requirement, and outcome were monitored. A response was defined as an increase in platelet count to ≥ 40,000/µl. Dogs in the prednisone group that failed to respond received 1 dose of vincristine on day 7. Results —Dogs that received prednisone and vincristine had a significantly faster increase in platelet count to ≥ 40,000/µl than dogs that received prednisone alone (mean ± SD, 4.9 ± 1.1 vs 6.8 ± 4.5 days, respectively). A similarly rapid response was observed in dogs that received vincristine on day 7 after treatment with prednisone alone failed. Furthermore, duration of hospitalization was reduced in the vincristine group, compared with the prednisone group (5.4 ± 0.3 vs 7.3 ± 0.5 days, respectively). No adverse effects attributable to vincristine were observed in any dog. Conclusions and Clinical Relevance —Administration of combined vincristine and prednisone is associated with more rapid increase in platelet numbers and shortened duration of hospitalization in dogs with IMT, compared with use of prednisone alone. Early use of vincristine seems warranted in dogs with severe primary IMT. ( J Am Vet Med Assoc 2002; 220:477–481)
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Abstract Second remission induction rates for vincristine and prednisone alone (VP) and vincristine, L‐asparaginase, and prednisone (VLP) are compared for children with acute lymphocytic leukemia. No evidence of a significant difference between the second induction complete remission rate for VP (78.6%) and VLP (73.7%) was found. Duration of first remission and prognostic group at initial diagnosis (defined on the basis of age and white blood count at initial diagnosis) are shown to be significant prognostic factors for second remission induction; and three second remission induction risk groups are defined on the basis of these two factors. Periodic reinforcement with prednisone in first remission does not appear to lower second induction complete response (CR) rates for VP. There was no evidence of a significant difference in the frequency of occurrence of severe toxicity between the VP and VLP regimens.
Acute lymphocytic leukemia
Induction chemotherapy
Spontaneous remission
White blood cell
Asparaginase
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T w o different regimens utilizing daunomycin, vincristine sulfate, and prednisone were administered in combination to treat 64 children with acute leukemia in relapse.All patients had received previous therapy with vincristine, prednisone, and/or daunomycin but none had received the 3 drugs in combination.Seven were known to be resistant to both vincristine and prednisone.The triple combination was effective in inducing remission in 44 of the children, but myelosuppression was severe and t h e results obtained were not significantly better than the much less toxic combination of vincristine and prednisone. HE ANTILEUKEhllC ACTIVITY OF DAUNOMY-T cin when used in combination with vincristine sulfate and prednisone has been studied by the Southwest Cancer Chemotherapy Study Group (SWCCSG).Daunomycin, an antibiotic isolated from cultures of Streptomyces peucetius, is capable of inhibiting growth of mammalian cells throughout the proliferative cycle.3Daunomycin complexes
Childhood leukemia
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Summary After complete remission had been induced by prednisone and vincristine in children with acute leukemia, hydroxyurea was used in an effort to maintain remission. No significant prolongation of remission occurred despite the appearance of toxicity in over 50% of the high dosage group. An equally significant observation was that the duration of remission produced by prednisone and vincristine was longer in those who had not received vincristine during a prior induced remission.
Spontaneous remission
Acute lymphocytic leukemia
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L-Asparaginase was added to vincristine and prednisone for induction of first remission in 815 children with acute lymphocytic or acute undifferentiated leukemia. This combination resulted in an overall remission rate of 93%. The addition of L-asparaginse to the standard induction regimen using prednisone and vincristine did not significantly increase the morbidity or mortality rate during the induction period. The most common side effect was transient L-asparaginase-induced hyperglycemia. The safe administration of L-asparaginase i.m. and the dose efficacy of 6000 I.U./sq m were confirmed. For these reasons, L-asparaginase should be combined with vincristine and prednisone for the initial induction of children with acute lymphocytic or acute undifferentiated leukemia.
Acute lymphocytic leukemia
Asparaginase
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Abstract Forty‐five children with acute nonlymphoblastic leukemia in relapse received a total of 56 courses of L‐asparaginase combined with vincristine and prednisone. The complete remission rate of 40% (12 of 30 trials) in patients resistant to vincristine and prednisone was almost identical to that in children still sensitive to vincristine and prednisone (42%, 11 of 26 trials). The complete remission rate of 38% (14 of 37 exposures) in those children who had not received L‐asparaginase previously compared favorably with the complete remission rate in those children who had received prior L‐asparaginase (47%, 9 of 19 exposures). Forty‐seven of the 56 induction trials were in children with 1 or more remissions and 14 of these were in children with 3 or more prior remissions. Toxicity was minimal.
Asparaginase
Induction chemotherapy
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Abstract Since 1970, 82 previously untreated adult patients with acute lymphocytic leukemia (ALL) were treated for induction of remission with combination chemotherapy either including vincristine and prednisone (18 patients), vincristine, prednisone and daunomycin (27 patients), or vincristine, prednisone, and asparaginase (37 patients). Upon achievement of complete remission patients were started on continuous maintenance with daily mercaptopurine, weekly methotrexate, and periodic vincristine and prednisone reinforcement pulses. Central nervous system prophylaxis consisted of six weekly intrathecal injections of methotrexate and prednisone given during induction, followed by monthly doses during maintenance. Overall, 55 of the 82 patients (67%) achieved complete remission; the addition of daunomycin or asparaginase to vincristine and prednisone did not significantly improve the response rate. Severe myelosuppression was common, being responsible for the death of 23 patients during induction. The predicted median duration of remission was 25 months, with 24 patients continuing in remission after 3.5–60 months. Duration of remission was significantly shorter in those patients who initially had a peripheral blood count greater than 50 × 10 9 /liter. The predicted median survival was 39.5 months in those who achieved remission, less than one month in those who did not, and 12 months overall.
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Acute lymphocytic leukemia
Induction chemotherapy
Asparaginase
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