Influence of dose reduction of vincristine in R-CHOP on outcomes of diffuse large B cell lymphoma

Abstract

Dose intensity (DI) of chemotherapy affects prognosis of diffuse large B cell lymphoma (DLBCL). Myelotoxicity is the major dose-limiting toxicity (DLT) of most cytotoxic agents for hematological malignancies, whereas DLT of vincristine (VCR) is mainly neurological toxicity. Although VCR is a key drug and its combination with other cytotoxic agents needs consideration, studies focused on relative DI (RDI) of VCR have not been done before. We retrospectively analyzed 86 cases of DLBCL that received six or more cycles of cyclophosphamide (CPM), doxorubicin (DXR), VCR, prednisolone, and rituximab [R-CHOP] and calculated RDI of each cytotoxic agent to analyze its influence on treatment outcome. The median RDI of CPM, doxorubicin, and VCR was 80.0, 81.7, and 78.4 %, respectively (p = 0.002). The average RDI (ARDI) of these three agents was 80.0 %. The overall survival was significantly worse in the low ARDI (<85 %) than in the high ARDI (>85 %) group (2-year survival rate 67.2 vs 93.4 %, p = 0.011). The survival rate with low RDI VCR (<85 %) was lower than that with high RDI VCR (>85 %), even when the remaining two agents had high ARDI (2-year survival rate 74.3 vs 95.8 %, p = 0.047). In conclusion, VCR dose tended to be reduced compared with CPM and DXR in R-CHOP. Lower ARDI of cytotoxic agents and lower RDI of VCR could lead to poor prognosis in the treatment of DLBCL with R-CHOP. We thought these observations should be confirmed in a prospective study.

Treatment approaches for older and oldest patients with diffuse large B-cell lymphoma – Use of non-R-CHOP alternative therapies and impact of comorbidities on treatment choices and outcome: A Humedica database retrospective cohort analysis, 2007–2015

“…Initial R-CHOP therapy for DLBCL patients, regardless of age, has been standard of care for the past decade. Maintenance of dose intensity is important in optimizing outcome with this regimen [13][14][15][16]. A variety of studies have been undertaken to improve upon outcome achieved with R-CHOP.…”

Impact of Pretreatment Neutrophil Count on Chemotherapy Administration and Toxicity in Dogs with Lymphoma Treated with CHOP Chemotherapy

“…Relative dose intensity may also be more heavily dependent on some drugs in the CHOP protocol. Indeed, a relative dose reduction in vincristine has been associated with poorer outcome in human patients diagnosed with diffuse large B‐cell lymphoma treated with R‐CHOP . In a recent study investigating the use of 25‐week CHOP in dogs, the authors suggested a temporal relationship existed between relapse of lymphoma and cyclophosphamide .…”

“…Indeed, a relative dose reduction in vincristine has been associated with poorer outcome in human patients diagnosed with diffuse large B-cell lymphoma treated with R-CHOP. 19 In a recent study investigating the use of 25-week CHOP in dogs, the authors suggested a temporal relationship existed between relapse of lymphoma and cyclophosphamide. 61 Although further investigation is necessary to confirm this observation, efforts could be focused on improving DI of drugs considered most useful for the disease.…”

“…4,5,16 In non-Hodgkin's lymphoma in humans, a decrease in chemotherapy relative dose intensity (RDI) has been associated with poorer outcome. [17][18][19][20][21] In dogs with lymphoma treated with a multidrug chemotherapy protocol, several studies suggested chemotherapy-induced neutropenia prolonged first remission duration. 22,23 It remains unclear, however, if RDI is directly associated with outcome in these dogs.…”

Control of Constipation in Patients Receiving CHOP or CHOP-Like Chemotherapy Regimens for Non-Hodgkin’s Lymphoma

“…This neurotoxicity is a dose-limiting toxicity for vincristine. 7) In their retrospective analysis, Utsu et al 8) demonstrated that a dose reduction in vincristine in patients receiving R-CHOP for diffuse large B cell lymphoma is associated with poor prognosis. 8) Therefore, prevention of vincristineinduced neurotoxicity is important to improve outcomes in patients with non-Hodgkin's lymphoma.…”