Treatment regimen and supportive care
| Drug . | Dose and route . | Duration . | Schedule . | Dose modifications for toxicity . |
|---|---|---|---|---|
| Rituximab | 375 mg/m2 IV infusion | Over 2-6 h | Before each EPOCH cycle (arm A) or weekly times 6 weeks after EPOCH completed (arm B) | Skin/mucositis: discontinue if attributed to rituximab |
| EPOCH | ||||
| Etoposide | 50 mg/m2/day by continuous IV infusion | 4 days (96 h) | Every 3 weeks | Hematolotogic*: reduce by 25%Renal: reduce to 25% if creatinine clearance < 40 mL/min |
| Doxorubicin | 10 mg/m2/day by continuous IV infusion | 4 days (96 h) | Every 3 weeks | Hematologic*: reduce by 25%Hepatic: reduce to 25% if direct bilirubin > 2.5 mg/dL |
| Vincristine | 0.4 mg/m2/day by continuous IV infusion | 4 days (96 h) | Every 3 weeks | Neurotoxicity: obstipation or unable to walk on heels, reduce to 0.3 mg/m2/day; difficulty ambulating, discontinueHepatic: reduce to 25% if direct bilirubin > 2.5 mg/dLRenal: reduce to 25% if creatinine clearance < 40 mL/min |
| Prednisone | 60 mg/m2 per day orally | 5 days | Every 3 weeks | |
| Cyclophosphamide | Cycle 1 187 mg/m2 IV if CD4 < 100/μL375 mg/m2 IV if CD4 > 100/μL | 60-minute infusion | Every 3 weeks after completion of etoposide, doxorubicin, vincristine infusion | Cycle 2-6: escalate dose in increments of 187 mg/m2 per cycle if neutrophil nadir > 500/μL and platelet nadir > 25 000/μL in preceding cycleReduce dose in increments of 187 mg/m2 if the nadir neutrophil count was < 500/μL or platelet nadir < 25 000/μL in preceding cycle |
| Supportive care | ||||
| Filgrastim (or pegfilgrastim) | 5 μg/kg subcutaneous injection (or pegfilgrastim 6 mg) ∼ 24 h after EPOCH completed | Daily until neutrophil recovery (or once for pegfilgrastim) | Begin on day 6 after EPOCH completed | |
| Trimethorprim-sulfamethoxazole | 160-800 mg PO | Continuous | 3× weekly (eg, Monday, Wednesday, Friday) | |
| Fluconazole | 100 mg PO | Continuous | Daily | |
| Ciprofloxacin | 500 mg PO BID (or alternative quinolone and dose at discretion of physician) | At least 8 days each cycle | Begin on day 8 of each cycle, continue until day 15 or postnadir neutrophil count ≥ 1000/μL |
| Drug . | Dose and route . | Duration . | Schedule . | Dose modifications for toxicity . |
|---|---|---|---|---|
| Rituximab | 375 mg/m2 IV infusion | Over 2-6 h | Before each EPOCH cycle (arm A) or weekly times 6 weeks after EPOCH completed (arm B) | Skin/mucositis: discontinue if attributed to rituximab |
| EPOCH | ||||
| Etoposide | 50 mg/m2/day by continuous IV infusion | 4 days (96 h) | Every 3 weeks | Hematolotogic*: reduce by 25%Renal: reduce to 25% if creatinine clearance < 40 mL/min |
| Doxorubicin | 10 mg/m2/day by continuous IV infusion | 4 days (96 h) | Every 3 weeks | Hematologic*: reduce by 25%Hepatic: reduce to 25% if direct bilirubin > 2.5 mg/dL |
| Vincristine | 0.4 mg/m2/day by continuous IV infusion | 4 days (96 h) | Every 3 weeks | Neurotoxicity: obstipation or unable to walk on heels, reduce to 0.3 mg/m2/day; difficulty ambulating, discontinueHepatic: reduce to 25% if direct bilirubin > 2.5 mg/dLRenal: reduce to 25% if creatinine clearance < 40 mL/min |
| Prednisone | 60 mg/m2 per day orally | 5 days | Every 3 weeks | |
| Cyclophosphamide | Cycle 1 187 mg/m2 IV if CD4 < 100/μL375 mg/m2 IV if CD4 > 100/μL | 60-minute infusion | Every 3 weeks after completion of etoposide, doxorubicin, vincristine infusion | Cycle 2-6: escalate dose in increments of 187 mg/m2 per cycle if neutrophil nadir > 500/μL and platelet nadir > 25 000/μL in preceding cycleReduce dose in increments of 187 mg/m2 if the nadir neutrophil count was < 500/μL or platelet nadir < 25 000/μL in preceding cycle |
| Supportive care | ||||
| Filgrastim (or pegfilgrastim) | 5 μg/kg subcutaneous injection (or pegfilgrastim 6 mg) ∼ 24 h after EPOCH completed | Daily until neutrophil recovery (or once for pegfilgrastim) | Begin on day 6 after EPOCH completed | |
| Trimethorprim-sulfamethoxazole | 160-800 mg PO | Continuous | 3× weekly (eg, Monday, Wednesday, Friday) | |
| Fluconazole | 100 mg PO | Continuous | Daily | |
| Ciprofloxacin | 500 mg PO BID (or alternative quinolone and dose at discretion of physician) | At least 8 days each cycle | Begin on day 8 of each cycle, continue until day 15 or postnadir neutrophil count ≥ 1000/μL |
IV indicates intravenous; PO, by mouth; and BID, twice a day.
Toxicity calling for dose reduction of doxorubicin and etoposide included a neutrophil nadir less than 500/μL for at least 3 days or platelets less than 25 000/μL for at least 3 days if this occurs during a cycle in which no cyclophosphamide was given; otherwise, doxorubicin/etoposide was not reduced.