Cancer · 2012
A phase 1 dose escalation study of bortezomib combined with rituximab, cyclophosphamide, doxorubicin, modified vincristine, and prednisone for untreated follicular lymphoma and other low-grade B-cell lymphomas.
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Sinha Rajni, Kaufman Jonathan L, Khoury Hanna Jean, King Nassoma, Shenoy Pareen J, Lewis Carol, Bumpers Kevin, Hutchison-Rzepka Amanda, Tighiouart Mourad, Heffner Leonard T, Lechowicz Mary Jo, Lonial Sagar, Flowers Christopher R
Аннотация
BACKGROUND: Bortezomib has demonstrated efficacy in patients with relapsed B-cell non-Hodgkin lymphoma (NHL) both alone and in combination with other agents; however, limited data exist regarding its toxicity in combination with common frontline therapies for indolent NHL. A phase 1 study of bortezomib combined with rituximab, cyclophosphamide, doxorubicin, modified vincristine, and prednisone (R-CHOP) was conducted in patients with untreated follicular lymphoma (FL) and other indolent NHLs.
METHODS: Nineteen patients, including 10 patients with FL, were enrolled. The median patient age was 59 years (range, 29-71 years). Seven patients had a FL International Prognostic Index score ≥3. R-CHOP with the vincristine dose capped at 1.5 mg was administered on a 21-day cycle for 6 to 8 cycles, and 1 of 3 dose levels of bortezomib (1.0 mg/m(2) [n = 1], 1.3 mg/m(2) [n = 6], or 1.6 mg/m(2) [n = 12]) was administered on days 1 and 8 of each cycle using a Bayesian algorithm for dose escalation.
RESULTS: The maximum tolerated dose (MTD) of bortezomib with modified R-CHOP was reached at 1.6 mg/m(2). Dose-limiting toxicity was observed in 5 patients (1 patient at a bortezomib dose of 1.0 mg/m(2), 1 patient at a bortezomib dose of 1.3 mg/m(2), and 3 patients at a bortezomib dose of 1.6 mg/m(2)). Neuropathy occurred in 16 patients (84%), including 2 patients (11%) who experienced grade 3 sensory neuropathy. Grade 4 hematologic toxicity occurred in 4 patients. Of 19 evaluable patients, 100% responded, and the complete response rate was 68%. At a median follow-up of 32 months, the 3-year progression-free survival rate was 89.5%.
CONCLUSIONS: Bortezomib combined with modified R-CHOP produced high response rates without substantial increases in toxicity. A phase 2 study of R-CHOP and bortezomib given at this established MTD is currently ongoing.
METHODS: Nineteen patients, including 10 patients with FL, were enrolled. The median patient age was 59 years (range, 29-71 years). Seven patients had a FL International Prognostic Index score ≥3. R-CHOP with the vincristine dose capped at 1.5 mg was administered on a 21-day cycle for 6 to 8 cycles, and 1 of 3 dose levels of bortezomib (1.0 mg/m(2) [n = 1], 1.3 mg/m(2) [n = 6], or 1.6 mg/m(2) [n = 12]) was administered on days 1 and 8 of each cycle using a Bayesian algorithm for dose escalation.
RESULTS: The maximum tolerated dose (MTD) of bortezomib with modified R-CHOP was reached at 1.6 mg/m(2). Dose-limiting toxicity was observed in 5 patients (1 patient at a bortezomib dose of 1.0 mg/m(2), 1 patient at a bortezomib dose of 1.3 mg/m(2), and 3 patients at a bortezomib dose of 1.6 mg/m(2)). Neuropathy occurred in 16 patients (84%), including 2 patients (11%) who experienced grade 3 sensory neuropathy. Grade 4 hematologic toxicity occurred in 4 patients. Of 19 evaluable patients, 100% responded, and the complete response rate was 68%. At a median follow-up of 32 months, the 3-year progression-free survival rate was 89.5%.
CONCLUSIONS: Bortezomib combined with modified R-CHOP produced high response rates without substantial increases in toxicity. A phase 2 study of R-CHOP and bortezomib given at this established MTD is currently ongoing.
Предметные рубрики MeSH
AdultAgedAntibodies, Monoclonal, Murine-DerivedAntineoplastic Combined Chemotherapy ProtocolsBoronic AcidsBortezomibCyclophosphamideDisease-Free SurvivalDoxorubicinDrug Administration ScheduleFemaleHumansLymphoma, B-CellLymphoma, FollicularMaleMaximum Tolerated DoseMiddle AgedNeural ConductionPrednisonePyrazinesRituximabVincristine