R-CHOP

Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone for large B-cell lymphoma

For clinicians and students · Regimen tutorial · Lymphoma · 10 min read · last reviewed September 30, 2026

Key points

R-CHOP-21 is the backbone first-line regimen for DLBCL: all drugs on Day 1 (prednisone Days 1 to 5), repeated every 21 days, usually for 6 cycles in advanced stage.
Protocols differ on prednisone and vincristine: BC Cancer LYCHOPR uses prednisone 45 mg/m2 and uncapped vincristine 1.4 mg/m2; eviQ uses prednisolone 100 mg flat and caps vincristine at 2 mg.
Screen HBsAg and anti-HBc before starting. Rituximab carries a very high risk of HBV reactivation, and positive patients need antiviral prophylaxis (entecavir preferred).
Assess tumour lysis risk, CNS relapse risk (CNS-IPI, testicular or renal involvement) and cardiac function before Cycle 1.
Six cycles give a cumulative doxorubicin dose of 300 mg/m2, the level at which BC Cancer recommends cardiac assessment.
Pola-R-CHP (POLARIX) is an alternative for higher-IPI disease, and BC Cancer now restricts it to the ABC subtype. FLYER supports 4 cycles of R-CHOP plus 2 of rituximab for young, low-risk patients.

Indications

R-CHOP is first-line therapy for diffuse large B-cell lymphoma (DLBCL) of any stage. BC Cancer LYCHOPR also lists mantle cell lymphoma, grade 3B follicular lymphoma and biopsy-confirmed or clinically suspected transformed lymphoma as eligible indications. eviQ ID 70 covers CD20-positive B-cell lymphomas generally.

Limited stage: BC Cancer gives 3 cycles of CHOP-R followed by radiotherapy.
Advanced stage: 6 cycles is the standard. BC Cancer allows extension to 8 cycles if circumstances warrant, and eviQ lists 6 to 8 cycles.
Alternatives to know: Pola-R-CHP is an option for IPI 2 to 5 disease (see Key trials). Under BC Cancer LYPOLARCHP it is restricted to activated B-cell (ABC) subtype confirmed by gene expression profiling. Patients at high risk of CNS relapse may receive CHOP-R with high-dose methotrexate (BC Cancer LYCHOPRMTX).

Regimen table

BC Cancer LYCHOPR (every 21 days):

Drug	Dose	Route	Day(s)	Notes
Doxorubicin	50 mg/m²	IV push	Day 1	Vesicant
Vincristine	1.4 mg/m²	IV in 25–50 mL NS over 15 min	Day 1	BC Cancer: no cap on dose
Cyclophosphamide	750 mg/m²	IV in 100–250 mL NS over 20–60 min	Day 1
Prednisone	45 mg/m²	PO, in the morning with food	Days 1–5	Round to nearest 25 mg. Take that day's dose on the morning of the rituximab infusion
Rituximab (IV)	375 mg/m²	IV in 250–500 mL NS over 90 min to 8 h	Day 1 or 2	Given whenever possible but no later than 72 h after CHOP, before or after chemotherapy. Dose-banded
Rituximab (SC), from Cycle 2 if the IV dose was tolerated	1400 mg fixed (11.7 mL)	SC into abdominal wall over 5 min	Day 1 or 2	The first dose must always be IV. Observe for 15 min after the injection

Cycle length: 21 days. BC Cancer also allows the next cycle sooner if counts have recovered enough for 100% dosing. Number of cycles: 3 cycles plus radiotherapy for limited stage, or 6 cycles for advanced stage (up to 8). Stop if there is no response after 2 cycles, and reassess after Cycles 4 and 6.

Main variant: eviQ ID 70 (R-CHOP21, v9, reviewed 11 Apr 2024):

Prednisolone 100 mg PO once daily, Days 1–5
Rituximab 375 mg/m² IV on Day 1
Doxorubicin 50 mg/m² IV on Day 1
Vincristine 1.4 mg/m² IV on Day 1, capped at 2 mg
Cyclophosphamide 750 mg/m² IV on Day 1
Every 21 days for 6 to 8 cycles

eviQ also notes two options:

Consider 4 cycles of R-CHOP21 followed by 2 cycles of rituximab alone for patients aged 60 or under with aaIPI 0 and no bulky disease (7.5 cm or more), based on FLYER.
Consider a prephase of prednisolone 100 mg PO daily for 5 to 7 days before Cycle 1 (RICOVER-60 precedent) in older or frail patients.

The flat 100 mg prednisone dose with a 2 mg vincristine cap is the most widely used convention internationally. The BC Cancer variant is body-surface-area based and does not cap vincristine. Follow whichever version your centre has approved.

IV rituximab infusion rates (BC Cancer):

First infusion: start at 50 mg/h. After 1 hour, increase by 50 mg/h every 30 min, to a maximum of 400 mg/h.
Later infusions: give 1/5 of the volume over 30 min, then the remaining 4/5 over 60 min (90 minutes in total).

Premedication & supportive care

Antiemetics: Protocols classify this regimen differently.
BC Cancer: highly emetogenic protocol (SCNAUSEA).
eviQ: moderate emetogenicity. The protocol prednisolone serves as the steroid, so no extra antiemetic steroid is added.
Rituximab premedication (BC Cancer):
Diphenhydramine 50 mg PO and acetaminophen 650–975 mg PO before rituximab, repeated every 4 hours if the infusion runs longer than 4 hours.
The protocol prednisone covers the steroid component.
Because transient hypotension can occur, consider holding antihypertensives for 12 hours before the infusion.
Hepatitis B screening and prophylaxis:
Check HBsAg, anti-HBs and anti-HBc at baseline. BC Cancer lets the first cycle proceed, but the results must be reviewed before Cycle 2.
Rituximab and other B-cell-depleting therapies are classed as very high risk for HBV reactivation.
If HBsAg or anti-HBc is positive, BC Cancer SCHBV recommends entecavir 0.5 mg PO daily (preferred) or tenofovir 300 mg PO daily. Start before chemoimmunotherapy and continue for 18 months after cancer treatment ends.
Monitor HBV DNA and ALT every 3 months, including for at least 12 months after the antiviral is stopped.
Consider involving hepatology (ASCO PCO 2020).
Tumour lysis syndrome: eviQ rates R-CHOP as high TLS risk and recommends prophylaxis.
Hydrate and give a uric acid-lowering agent per local TLS guidelines. Rasburicase is used for high-risk patients.
When disease is very bulky, eviQ suggests giving the first rituximab dose on the day before CHOP.
Some clinicians omit rituximab from Cycle 1 when the circulating lymphocyte count exceeds 30–50 × 10⁹/L, because the risk of cytokine release is higher.
Growth factors: BC Cancer LYCHOPR does not use primary G-CSF.
It recommends G-CSF after a nadir ANC below 0.8 × 10⁹/L in curative-intent treatment, while keeping 100% doses: filgrastim 5 mcg/kg daily for 5 days from Day 7, or pegfilgrastim 6 mg on Day 7.
Many international guidelines recommend primary prophylaxis for older patients, whose febrile neutropenia risk is high.
Pneumocystis (PJP) and antiviral/antifungal prophylaxis: follow institutional policy, which eviQ also defers to. PJP prophylaxis is commonly given with dose-dense R-CHOP-14 or prolonged corticosteroids.
Steroid effects: monitor glucose in patients with diabetes, and consider a PPI or H2 blocker.
Bowel care: start a prophylactic bowel regimen because vincristine causes constipation.
Vaccines: avoid live vaccines.

Key toxicities

Myelosuppression and febrile neutropenia: the nadir usually falls around Days 7–14.
Rituximab infusion reactions and cytokine release syndrome: risk is highest with the first infusion. Severe CRS usually begins within 1–2 hours and presents with dyspnoea, bronchospasm, hypoxia and rigors. BC Cancer warns it can be fatal and may be accompanied by features of tumour lysis syndrome.
Anthracycline cardiomyopathy: risk depends on cumulative dose (see Monitoring).
Vincristine neurotoxicity: sensory neuropathy, constipation or ileus, jaw pain, and rarely autonomic or cranial neuropathy. Vincristine must never be given intrathecally. Dispense it in a minibag per safety alerts.
Extravasation: doxorubicin and vincristine are vesicants.
HBV reactivation: can cause fulminant hepatitis.
Rituximab-specific risks: late neutropenia, hypogammaglobulinaemia, progressive multifocal leukoencephalopathy (rare), and rare severe mucocutaneous reactions resembling SJS. Stop rituximab if a mucocutaneous reaction occurs.
GI obstruction or perforation: rare and sometimes fatal, typically 1–12 weeks after treatment, particularly with bowel involvement.
Corticosteroid effects: hyperglycaemia, insomnia, mood change and infection risk.
Cyclophosphamide effects: haemorrhagic cystitis is uncommon at this dose. Fertility effects are possible.
Alopecia and mucositis.

Monitoring

Baseline (BC Cancer): CBC and differential, creatinine, ALT and bilirubin, plus HBV serology (see above).
Baseline cardiac function: eviQ recommends a baseline echocardiogram or gated heart pool scan and an ECG, especially in older patients and those with cardiac risk factors.
Before each cycle: CBC and differential, creatinine, ALT and bilirubin.
As indicated: LDH, electrolytes, calcium, uric acid and phosphate. Monitor TLS laboratory values after Cycle 1 in high-risk patients.
Cardiac: BC Cancer recommends cardiac assessment once the cumulative doxorubicin dose reaches 300 mg/m² or more (six cycles of 50 mg/m²). Count all prior anthracyclines.
Neuropathy: check fine motor tasks such as buttoning and writing before each vincristine dose.
Response: interim imaging per protocol and end-of-treatment PET-CT.

Dose-modification principles

Summarized from BC Cancer LYCHOPR. Local protocols vary, so defer to yours.

Older patients (over 75):
Give cyclophosphamide and doxorubicin at 75% for Cycle 1, then escalate toward full dose as tolerated.
In very elderly or frail patients, reduced-intensity R-mini-CHOP is a separate option not covered here.
Haematological (doxorubicin and cyclophosphamide):
Nadir ANC of 0.8 × 10⁹/L or more: give 100%.
Nadir ANC below 0.8: continue at 100% and add G-CSF. The protocol's aim is to keep dose intensity in curative treatment rather than reduce doses.
Vincristine neuropathy:
Dysaesthesias or areflexia only: 100%.
Difficulty buttoning or writing: 67%.
Moderate motor neuropathy: 50%.
Severe motor neuropathy: omit.
Hepatic, by total bilirubin:
Doxorubicin: 2–35 µmol/L, 100%. 36–85, 50%. Above 85, omit doxorubicin and add cyclophosphamide 350 mg/m².
Vincristine: 25 µmol/L or less, 100%. 26–50, 50%. Above 50, 25%.
These adjustments usually apply only to initial treatment while jaundice resolves.
Proven cardiac dysfunction: BC Cancer allows replacing doxorubicin with etoposide 50 mg/m² IV on Day 1 plus 100 mg/m² PO on Days 2–3.
Renal (eviQ): reduce cyclophosphamide by 25% if CrCl is below 10 mL/min. eviQ notes that renal recommendations are being realigned with the ADDIKD guideline.

Key trials & evidence

GELA LNH98-5 (Coiffier, NEJM 2002): in patients aged 60–80 with DLBCL, 8 cycles of R-CHOP improved complete response, event-free survival and overall survival compared with CHOP. The benefit persisted on long-term follow-up.
MInT (Pfreundschuh, Lancet Oncol 2006): in younger good-prognosis patients, adding rituximab to CHOP-like chemotherapy improved event-free and overall survival.
R-CHOP-14 versus R-CHOP-21 (Cunningham, Lancet 2013; Delarue, Lancet Oncol 2013): the 14-day schedule gave no survival advantage. R-CHOP-21 remains standard.
FLYER (Poeschel, Lancet 2019): in patients aged 18–60 with aaIPI 0 and non-bulky disease, 4 cycles of R-CHOP plus 2 of rituximab were non-inferior to 6 cycles of R-CHOP, with less toxicity.
S1001 (Persky, JCO 2020): in limited-stage non-bulky disease, PET-negative patients after 3 cycles of R-CHOP did well with one more cycle and no radiotherapy. This supports PET-adapted de-escalation, and practice varies by centre.
POLARIX (Tilly, NEJM 2022): in IPI 2–5 DLBCL, pola-R-CHP (polatuzumab vedotin replacing vincristine) improved progression-free survival over R-CHOP (HR about 0.73), with similar safety. An overall survival difference was not shown at the primary analysis. Subgroup analyses suggested the benefit is concentrated in ABC/non-GCB disease, which is why BC Cancer restricts LYPOLARCHP to the ABC subtype.
CNS-IPI (Schmitz, JCO 2016): stratifies CNS relapse risk using the IPI factors plus kidney or adrenal involvement. The high-risk group has about a 10% 2-year risk of CNS relapse.

CNS prophylaxis considerations

Who is at risk: estimate CNS relapse risk at diagnosis using the CNS-IPI and specific sites. Testicular, renal or adrenal, breast and uterine involvement carry higher risk, as do high-grade B-cell lymphoma with MYC/BCL2 rearrangement and intravascular lymphoma.
Staging: consider CSF cytology and flow cytometry, with or without MRI, in high-risk patients.
Evidence for prophylaxis is weak:
Large retrospective series have not shown that high-dose methotrexate prophylaxis reliably prevents CNS relapse.
The benefit of intrathecal prophylaxis is also uncertain.
Practice is moving toward selective use, mainly in testicular lymphoma and very high-risk cases, and patient-level decisions after discussion at a lymphoma conference.
BC Cancer LYCHOPRMTX: reserves CHOP-R with high-dose methotrexate for testicular DLBCL of any stage, advanced DLBCL with renal involvement, or advanced disease with other high-risk features. It requires CrCl of 60 mL/min or more and no third-space fluid.

Clinical pearls

Prescribe HBV serology at the same time you order the staging PET, so results are available before Cycle 2 at the latest.
In R-CHOP, rituximab is given once per cycle with CHOP, not weekly as in single-agent schedules.
The first rituximab dose is always IV. Patients who have been off rituximab for more than 6 months restart with an IV dose.
IV and SC rituximab are different products. SC rituximab contains hyaluronidase, so give other SC drugs at a different site.
Six cycles deliver 300 mg/m² of doxorubicin, the cardiac-assessment threshold. Account for any earlier anthracycline exposure.
A prednisone prephase can improve performance status and reduce first-cycle toxicity in older, frail or bulky-disease patients.
Vincristine: one wrong route is fatal. Minibag dispensing and labelling "For intravenous use only – fatal if given by other routes" are safety standards.
Warn patients about constipation. Early laxatives prevent vincristine-related ileus.
Keep dose intensity in curative treatment by using G-CSF rather than reducing doses, per BC Cancer.

Sources

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