CHOP (chemotherapy)

Infusion of R,C,H and O components of R-CHOP. Red flask contains doxorubicin (H), the most toxic component. Prednisolone (P) is administered on the next four or five days intravenously or in tablets.[1]

CHOP is the acronym for a chemotherapy regimen used in the treatment of non-Hodgkin lymphoma. CHOP consists of:

Sometimes the chimeric anti-CD20 monoclonal antibody, rituximab, is added to this treatment regimen to form the R-CHOP regimen.

Dosing regimen

Drug Standard [R]-CHOP-14 or [R]-CHOP-21 [R]-miniCHOP[2] [R]-Maxi-CHOP Mode Days
(R)ituximab 375 mg/m2 375 mg/m2 375 mg/m2 IV infusion Day 1
(C)yclophosphamide 750 mg/m2 400 mg/m2 1200 mg/m2 IV infusion Day 1
(H)ydroxydaunorubicin 50 mg/m2 25 mg/m2 75 mg/m2 IV bolus Day 1
(O)ncovin 1.4 mg/m2 (max. 2 mg) 1 mg 2 mg IV bolus Day 1
(P)rednisone or (P)rednisolone 40 mg/m2 40 mg/m2 100 mg PO qd Days 1-5

R-miniCHOP is indicated in elderly patients (>80 years) with diffuse large B-cell lymphoma due to less toxicity from the reduced dose in comparison to R-CHOP.

R-Maxi-CHOP is used in mantle cell lymphoma and is given in 21-day intervals, alternating with R-HDAC (rituximab + high-dose cytarabine).[3]

In most other non-Hodgkin lymphomas (excluding some aggressive forms), standard-dose [R]-CHOP is generally used as first-line therapy.

Uses and indications

Normal cells are more able than cancer cells to repair damage from chemotherapy drugs.

This regimen can also be combined with the monoclonal antibody rituximab if the lymphoma is of B cell origin; this combination is called R-CHOP. In 2002, a randomized controlled trial showed a higher complete response rate for R-CHOP vs CHOP in elderly patients with Diffuse Large-B-Cell Lymphoma (76% vs 63%).[4] Typically, courses are administered at an interval of two or three weeks (CHOP-14 and CHOP-21 respectively). A staging CT scan is generally performed after three cycles to assess whether the disease is responding to treatment.

In patients with a history of cardiovascular disease, doxorubicin (which is cardiotoxic) is often deemed to be too great a risk and is omitted from the regimen. The combination is then referred to as COP (cyclophosphamide, Oncovin, and prednisone or prednisolone) or CVP (cyclophosphamide, vincristine, and prednisone or prednisolone).

As elderly patients have a greater risk of toxicity from the drugs, an option is to use an attenuated drug regimen, called miniCHOP.

Side-effects and complications

The combination is generally well tolerated.[5] Chemotherapy-induced nausea and vomiting may require antiemetics (such as ondansetron), and hemorrhagic cystitis is prevented with administration of mesna. Alopecia (hair loss) is common.[5]

Neutropenia generally develops in the second week. During this period, many clinicians recommend pegfilgrastim or prophylactic use of ciprofloxacin.[1] If a fever develops in the neutropenic period, urgent medical assessment is required for neutropenic sepsis, as infections in patients with low neutrophil counts may progress rapidly.

Allopurinol is typically co-administered prophylactically to prevent hyperuricemia that results from tumor lysis syndrome, the result of rapid death of tumor cells.[citation needed]

History

A pivotal study published in 1993 compared CHOP to several other chemotherapy regimens (e.g. m-BACOD, ProMACE-CytaBOM, MACOP-B) for advanced non-Hodgkin's lymphoma.[2] CHOP emerged as the regimen with the least toxicity but similar efficacy.

However, in Germany in 2012, bendamustine has displaced [R-]CHOP to become the first line treatment of choice for indolent lymphoma (a less aggressive subset of non-Hodgkin lymphoma).[6]

[R]-CHOEP modification

In order to develop more effective first-line chemotherapy regimen for aggressive lymphomas, some researchers tried to add (E)toposide to the standard [R]-CHOP regimen.[7]

There were also attempts to further improve the efficacy of the [R]-CHOEP regimen with escalating the chemotherapy doses. This mode was called [R]-High-CHOEP. However, it did not show more effectiveness than standard-dose [R]-CHOEP while adding more toxicity and cost.[8]

In order to try improving efficacy of the [R]-CHOEP, some researchers tried to escalate chemotherapy to very high doses, requiring autologous stem cell support in each cycle. Doses in that regimen were increased from cycle to cycle. This regimen was called [R]-MegaCHOEP. But again, such escalation seemed to not improve effectiveness while adding toxicity.[9]

Drug Standard [R]-CHOEP [R]-High-CHOEP [R]-Mega-CHOEP, cycle 1 [R]-Mega-CHOEP, cycles 2 and 3 [R]-Mega-CHOEP, cycle 4 (last) Mode Days
(R)ituximab 375 mg/m2 375 mg/m2 375 mg/m2 375 mg/m2 375 mg/m2 IV infusion Day 1
(C)yclophosphamide 750 mg/m2 1400 mg/m2 1500 mg/m2 4500 mg/m2 6000 mg/m2 IV infusion Day 1
(H)ydroxydaunorubicin 50 mg/m2 65 mg/m2 70 mg/m2 70 mg/m2 70 mg/m2 IV bolus Day 1
(O)ncovin 1.4 mg/m2 (max 2 mg) 2 mg 2 mg 2 mg 2 mg IV bolus Day 1
(E)toposide 100 mg/m2 175 mg/m2 600 mg/m2 960 mg/m2 1480 mg/m2 IV infusion Days 1-3
(P)rednisone or (P)rednisolone 40 mg/m2 100 mg 500 mg 500 mg 500 mg PO qd Days 1-5

See also

References

  1. ^ Cullen M, Steven N, Billingham L, Gaunt C, Hastings M, Simmonds P, Stuart N, Rea D, Bower M, Fernando I, Huddart R, Gollins S, Stanley A (2005). "Antibacterial prophylaxis after chemotherapy for solid tumors and lymphomas". N Engl J Med. 353 (10): 988–98. doi:10.1056/NEJMoa050078. PMID 16148284.
  2. ^ Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, Glick JH, Coltman CA Jr, Miller TP (1993). "Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin's lymphoma". N Engl J Med. 328 (14): 1002–6. doi:10.1056/NEJM199304083281404. PMID 7680764.
  1. ^ "R-CHOP". Cancer Research UK. Archived from the original on 2024-05-16. Retrieved 2024-05-16.
  2. ^ "Archived copy". Archived from the original on 2024-03-25. Retrieved 2024-03-25.{{cite web}}: CS1 maint: archived copy as title (link)
  3. ^ "Nordic Protocol (Maxi-CHOP and High Dose Cytarabine) for Mantle Cell Lymphoma (MCL)" (PDF). Archived from the original (PDF) on 2014-09-11. Retrieved 2014-09-11.
  4. ^ Coiffier B, Lepage E, Briere J, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002 Jan 24;346(4):235-42. doi: 10.1056/NEJMoa011795. PMID 11807147.
  5. ^ a b "R-CHOP - Macmillan Cancer Support". Archived from the original on 2018-12-15. Retrieved 2017-02-19.
  6. ^ "New Combo Replaces CHOP for Lymphoma. Dec 2012". Archived from the original on 2014-09-11. Retrieved 2012-12-13.
  7. ^ "Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of young patients with good-prognosis (normal LDH) aggressive lymphomas: results of the NHL-B1 trial of the DSHNHL". Archived from the original on 2019-04-02. Retrieved 2014-09-11.
  8. ^ Dose-escalated CHOEP for the treatment of young patients with aggressive non-Hodgkin's lymphoma: II. Results of the randomized high-CHOEP trial of the German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL)[dead link]
  9. ^ "Conventional chemotherapy (CHOEP-14) with rituximab or high-dose chemotherapy (MegaCHOEP) with rituximab for young, high-risk patients with aggressive B-cell lymphoma: an open-label, randomised, phase 3 trial (DSHNHL 2002-1)" (PDF). Archived from the original (PDF) on 2014-09-11. Retrieved 2014-09-11.