CHOP chemotherapy for the treatment of canine multicentric T‐cell lymphoma
Robert B. RebhunMichael S. KentS. A. E. B. BorrofkaSara D. AllstadtKatherine A. SkorupskiCarlos O. Rodriguez
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Abstract:
Dogs with multicentric T‐cell lymphoma are commonly treated with CHOP chemotherapy protocols that include cyclophosphamide, doxorubicin, vincristine and prednisone. The purpose of this study was to evaluate the use of CHOP chemotherapy for dogs with multicentric T‐cell lymphoma. Identification of prognostic factors in this specific subset of dogs was of secondary interest. Twenty‐three out of 24 dogs responded to CHOP chemotherapy and these dogs remained on the protocol for a median of 146 days. No variable was associated with progression free survival (PFS) including stage, substage, hypercalcemia or radiographic evidence of a cranial mediastinal mass. The median overall survival time (OST) for all dogs was 235 days. Dogs that were thrombocytopenic at presentation experienced a significantly longer OST (323 versus 212 days, P = 0.01).Keywords:
Canine Lymphoma
Dose intense CHOP protocols have been shown to improve outcome for people with non-Hodgkin's lymphoma, but evaluation of dose intense CHOP protocols for canine lymphoma is currently limited. The hypothesis of this retrospective study was that a 15-week dose intense CHOP protocol would have shorter treatment duration with similar efficacy to other doxorubicin-based multidrug protocols. Thirty-one client owned dogs with multicentric lymphoma were treated with a 15-week CHOP chemotherapy protocol with an overall response rate of 100% and a median progression-free interval (PFI) of 140 days [95% confidence interval (CI) 91-335 days]. Dogs that had two or more treatment delays had significantly prolonged PFI and overall survival in multivariate analysis. Dose intensity did not correlate with patient outcome. Dogs experiencing multiple treatment delays secondary to adverse events may receive their individual maximally tolerated dose while dogs with no adverse events may be underdosed. Future studies should focus on individual patient dose optimization.
Canine Lymphoma
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Despite high initial response rates, a subset of dogs with B-cell lymphoma responds less robustly to CHOP-based chemotherapy and experiences shorter survival. One hundred and four dogs with nodal B-cell lymphoma were treated with a response-based CHOP (RBCHOP) protocol modified based on response to individual drugs during the first chemotherapy cycle. Dogs achieving complete (CR) or partial response (PR) at week 3, following treatment with vincristine and cyclophosphamide, received RBCHOP 1 (n = 72), a protocol sequentially rotating vincristine, cyclophosphamide, and doxorubicin. Dogs without a detectable response at week 3 that subsequently achieved CR or PR following treatment with doxorubicin received RBCHOP 2 (n = 14), in which four doses of doxorubicin were given consecutively followed by vincristine and cyclophosphamide. Dogs that failed to respond at week 3 and then to doxorubicin at week 5 assessment were offered rescue chemotherapy (RBCHOP 3, n = 18). Median progression free survival (PFS) and overall survival time (OST) were similar between RBCHOP 1 (PFS 210 days, OST 354 days) and RBCHOP 2 (PFS 220 days, OST 456 days), but significantly shorter for RBCHOP 3 (PFS 34 days, OST 80.5 days, P < 0.001). No presenting signalment nor hematologic variable differentiated patient cohort, however, dogs in RBCHOP 2 and RBCHOP 3 were more likely to have a lymphocytosis at diagnosis (P = 0.02 and 0.04, respectively). Protocol modification based on response during the first cycle resulted in similar toxicity profiles and outcomes to previously published variants of CHOP, and prognosis remained poor for dogs failing to respond during the first treatment cycle.
Canine Lymphoma
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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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Dogs with multicentric T‐cell lymphoma are commonly treated with CHOP chemotherapy protocols that include cyclophosphamide, doxorubicin, vincristine and prednisone. The purpose of this study was to evaluate the use of CHOP chemotherapy for dogs with multicentric T‐cell lymphoma. Identification of prognostic factors in this specific subset of dogs was of secondary interest. Twenty‐three out of 24 dogs responded to CHOP chemotherapy and these dogs remained on the protocol for a median of 146 days. No variable was associated with progression free survival (PFS) including stage, substage, hypercalcemia or radiographic evidence of a cranial mediastinal mass. The median overall survival time (OST) for all dogs was 235 days. Dogs that were thrombocytopenic at presentation experienced a significantly longer OST (323 versus 212 days, P = 0.01).
Canine Lymphoma
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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
Regimen
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Cyclophosphamide exhibits the weakest therapeutic effect compared with vincristine and doxorubicin in the CHOP (C, cyclophosphamide; H, doxorubicin; O, vincristine; and P, prednisolone) chemotherapeutic protocol for the treatment of canine lymphoma. Twenty dogs with multicentric lymphoma were treated using the LHOP protocol, which used l-asparaginase in place of cyclophosphamide, and the outcomes were historically compared with those of dogs that received CHOP chemotherapy in the same institution. No significant differences were found in age (p = 0.107), body weight (p = 0.051), sex (p = 0.453), clinical stage V (p = 1), substage b (p = 0.573), T-cell phenotype (p = 0.340), overall response (p = 1), and hypercalcaemia status (p = 1) between the LHOP and CHOP groups. The adverse effects of l-asparaginase were well tolerated and self-limiting. The median PFS (progression-free survival) and median ST (survival time) in the LHOP group were 344 days (range: 28–940 days) and 344 days (range: 70–940 days), respectively. The median PFS and median ST in the CHOP group were 234 days (range: 49–1822 days) and 314 days (range: 50–1822 days), respectively. The dogs that received LHOP chemotherapy had a significantly longer PFS than the dogs that received CHOP chemotherapy (p = 0.001). No significant difference was observed in ST between the LHOP and CHOP groups (p = 0.131). Our study findings thus indicate that the LHOP protocol can be used as a first-line chemotherapeutic protocol in canine multicentric lymphoma.
Canine Lymphoma
Prednisolone
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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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