R-CHOP 14 - Rituximab 375 / Cyclophosphamide 750 / Doxorubicin 50 / Vincristine 2 / Prednisolone 100, diffuse large B-non-Hodgkin Lymphoma, cycle 1-6

Indication(s)

• NHL, B-Cell Type, Diffuse Large Cell; ICD-10 C83.3
• NHL, B-Cell Type, Follicular grade IIIb; ICD-10 C82.-, C82.7, C82.9

Protocol classification

• Classification: current standard
• Intensity: Standard dose
• Therapy mode: First line
• Therapy intention: curative

Cycles

Cycle length 14 days, recommended cycles: 6

Protocol sequences

• R-CHOP 14 (RITU375/CYCL750/DOXO50/VNCR2/PRED100), DLBCL, C1-6 (PID112) -|- RITU375, C7-8 (PID1448)

Risks

• Emetogenicity (MASCC/ESMO): moderate (30-90%)
• Neutropenia: very high (>41%)
• Febrile Neutropenia: high (>20%)
• Anemia Hb below 8g/dl: high (16-30%)
• Neuropathy: CTC AE °3-4: 7%

Therapy

Concomitant therapy supplements

In contrast to the primary literature, prednisolone is used instead of prednisone because of more favorable pharmacokinetics at the same potency. Dexamethasone for antiemesis on days 1-4 and prednisolone of allergy prophylaxis is covered by prednisolone of antitumor therapy. The combination of an anthracycline and cyclophosphamide may be highly emetogenic in individual patients and require the addition of a neurokinin receptor antagonist. In this case, attention must be paid to the increase in plasma concentration of prednisolone and this may need to be adjusted. Observe tumor lysis syndrome risk classification according to Cairo 2010; for LDH elevation without tumor bulk, use protocol "Tumor lysis syndrome prophylaxis, intermediate risk". In case of LDH elevation above twice the upper limit and tumor-bulk protocol use "tumor lysis syndrome prophylaxis, high risk".

Warnings

Doxorubicin: increased risk of cardiomyopathy, maximum cumulative dose 450-550 mg/m² KOF. In mediastinal irradiation, arterial hypertension for more than 5 years, age over 70 years or previous cardiac damage, maximum 400 mg/m². For DOXO extravasation: dry cold (not just before or after Dexrazoxane infusion) on day of extravasation. Dexrazoxane i.v. for 3 days: 2 days 1000 mg/m², 3rd day 500 mg/m², do not use in parallel with DMSO. First infusion as soon as possible and within the first 6 hours.

Notes

Following combined chemo-immunotherapy, 2 additional cycles of rituximab mono are administered 14 days apart (RITU single dose).

Cycles

Cycle length 14 days, recommended cycles: 6

Controls:

• Blood count: on day 1 and subsequently weekly
• Day -1: Echocardiography, ECG, chest X-ray Cardiotoxicity of doxorubicin, review of cardiac function before/under therapy recommended.
• Day -1: Hepatitis B (HBV) Test: HBsAg and anti-HBc Rituximab: Hep-B reactivation possible. If Hep-B serology is positive, initiate measures to prevent hepatitis B reactivation.
• Day -1: IgG Rituximab: Risk of Infection: It is recommended that immunoglobulin levels be determined prior to initiating treatment with rituximab.
• Day 1: GOT, GPT, GGT, Bilirubin, AP, Cholinesterase Doxorubicin: continuous liver monitoring is necessary during therapy. In case of elevated bilirubin, dose adjustment may be necessary. Cyclophosphamide: dose reduction may be necessary if liver function is impaired. Vincristine: dose reduction recommended in patients with impaired liver function.
• Day 1: Creatinine, glomerular filtration rate (GFR) Doxorubicin: Dose reduction necessary in patients with renal impairment. Cyclophosphamide: Dose reduction is usually recommended in the presence of impaired renal function.
• Day 1: Urine status Urinary sediment must be checked regularly for erythrocytes and other signs of uro/nephrotoxicity.
• Day 1: Na⁺, K⁺, Ca²⁺, Mg²⁺ Cyclophosphamide: exclusion of electrolyte disturbances before use.

Pharmacokinetics

Doxorubicin: hauptsächlich hepatobiliäre Elimination

Original indication

Aggressive B-NHL, 61-80 years, first-line, ECOG 0-2.

Original author

Pfreundschuh M (2006)

Origin

German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL), RICOVER-60

References

• Pfreundschuh M, Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60). Lancet Oncol 2008 Feb;9(2):105-16. doi: 10.1016/S1470-2045(08)70002-0. PMID: 18226581. [PMID]
• Brusamolino E, Dose-dense R-CHOP-14 supported by pegfilgrastim in patients with diffuse large B-cell lymphoma: a phase II study of feasibility and toxicity. Haematologica 2006 Apr;91(4):496-502. PMID: 16537117. [PMID]
• Cunningham D, Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: a phase 3 comparison of dose intensification with 14-day versus 21-day cycles. Lancet 2013 May 25;381(9880):1817-26. doi: 10.1016/S0140-6736(13)60313-X. PMID: 23615461. [PMID]

Recommendations

• 10/2015: European Society for Medical Oncology
• 05/2021: National Comprehensive Cancer Network

Status

Valid since 2015-01-19, Version 1.1, last updated 2021-06-04

Last modification: V1.1: Cato check successful. Vincristine is applied as a short infusion over 3 minutes according to the recommended course of action. V1.0: Run times according to the respective summary of product characteristics. In the study, a Pre-phase therapy was initially performed in each patient, this is shown in the protocol Pre-phase, aggr. B-NHL. After the 6 cycles, 2 additional administrations of rituximab were to be given, each 2 weeks apart; the RITU1400 single administration s.c. or RITU375 single administration protocol can be used for this purpose. Only patients older than 60 years were recruited.

Important notice

The copyrighted protocols are treatment recommendations. The information contained in this compilation on cytostatic drugs, concomitant medication and other therapeutic procedures, as well as dosage and application information, is continuously reviewed with all due care by the authors and editors involved. Nevertheless, the publishers and authors do not assume any liability for the correctness - also with regard to possible printing errors.

The protocols may not be changed in terms of content.

Diagnosis, indication for therapy and treatment of malignant diseases must be carried out in each individual case by the hematologist and oncologist on his or her own responsibility. The treating physician is obligated to this personal responsibility to weigh in each case before a diagnostic or therapeutic measure, indication, contraindications, dosage and application under consideration of the specialized information or other documents of the manufacturers. This applies in particular to rarely used preparations or preparations that are new to the market.

The publishers and authors assume no liability for the accuracy of the contents. The application is at the own responsibility of the treating physician. ©Onkopti.