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Non-Hodgkin's Lymphoma

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Adult Non-Hodgkin Lymphoma Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Treatment for Aggressive, Noncontiguous Stage II / III / IV Adult NHL

The treatment of choice for patients with advanced stages of aggressive non-Hodgkin lymphoma (NHL) is combination chemotherapy, either alone or supplemented by local-field radiation therapy.[1]

The following drug combinations are referred to in this section:

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Understanding Non-Hodgkin Lymphoma -- Symptoms

Symptoms of non-Hodgkin lymphoma may include: Painless swelling of one or more lymph nodes, with no recent infection. Swelling may be intermittent. Swelling, fluid accumulation, or pain in the abdomen. Shortness of breath, wheezing, or coughing. Bloody stool or vomit. Swelling of the face, neck, and arms. Blockage of urine flow. Bone pain. Unexplained weight loss amounting to 10% of body weight over six months. Fever lasting for at least 14 consecutive days, usually in...

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  • ACVBP: doxorubicin + cyclophosphamide + vindesine + bleomycin + prednisone.
  • CHOP: cyclophosphamide + doxorubicin + vincristine + prednisone.
  • CNOP: cyclophosphamide + mitoxantrone + vincristine + prednisone.
  • m-BACOD: methotrexate + bleomycin + doxorubicin + cyclophosphamide + vincristine + dexamethasone + leucovorin.
  • MACOP-B: methotrexate + doxorubicin + cyclophosphamide + vincristine + prednisone fixed dose + bleomycin + leucovorin.
  • ProMACE CytaBOM: prednisone + doxorubicin + cyclophosphamide + etoposide + cytarabine + bleomycin + vincristine + methotrexate + leucovorin.
  • R-CHOP: rituximab, an anti-CD20 monoclonal antibody, + cyclophosphamide + doxorubicin + vincristine + prednisone.

Standard Treatment Options for Aggressive, Noncontiguous Stage II/III/IV Adult NHL

Standard treatment options for Aggressive, Noncontiguous Stage II/III/IV Adult NHL include the following:

  1. R-CHOP.
  2. Other combination chemotherapy.

R-CHOP

The following studies established R-CHOP as the standard regimen for newly diagnosed patients with diffuse large B-cell lymphoma.[2]

Evidence (R-CHOP):

  1. The combination of rituximab and CHOP (R-CHOP) showed improvement in event-free survival (EFS) and overall survival (OS) compared with CHOP alone in 399 advanced-stage patients with diffuse large B-cell lymphoma older than 60 years (EFS = 57% vs. 38%, P = .002, and OS = 70% vs. 57%, P = .007 at 2 years).[3][Level of evidence: 1iiA] At 10-years' median follow-up, the OS of patients who received R-CHOP compared with patients who received CHOP was 44% versus 28%, P < .0001.[4]
  2. Similarly, for 326 evaluable patients younger than 61 years, R-CHOP showed improvement in EFS and OS compared with CHOP alone (EFS = 79% vs. 59%, P = .001, and OS = 93% vs. 84%, P = .001 at 3 years).[5][Level of evidence: 1iiA]
  3. A randomized study (DSHNHL-1999-1A) of 1,222 patients older than 60 years compared R-CHOP given every 2 weeks for six or eight cycles to CHOP given every 2 weeks for six or eight cycles.[6] With a median follow-up of 35 months, the EFS favored R-CHOP given every 2 weeks for six or eight cycles (EFS, relative risk [RR] = 0.5 [0.40–0.65], P < .001). The OS favored R-CHOP for only six cycles because of increased toxicity in the eight-cycle arm (RR of death = 0.63 [0.46–0.85], P = .003).[6][Level of evidence: 1iiA] There was no comparison to standard R-CHOP or CHOP given every 3 weeks.

Evidence (CHOP with or without other therapies):

  1. A trial of 380 patients younger than 60 years with diffuse large B-cell lymphoma and an age-adjusted International Prognostic Index (IPI) rating of 1 randomized treatment to ACVBP + rituximab (R-ACVBP) versus CHOP + rituximab.[7] With a median follow-up of 44 months, 3-year OS favored R-ACVBP (92% vs. 84%; HR, 0.44; 95% CI, 0.28–0.81, P = .007).[7][Level of evidence: 1iiA] The significantly worse toxicities with R-ACVBP, the narrow target population (<60 y with either elevated LDH or stage III/IV disease, but not both), and the lack of a confirmatory trial may inhibit adoption of R-ACVBP as a new standard of care.
  2. Two prospective randomized trials that compared CHOP with CNOP for patients aged 60 years and older with diffuse large cell lymphoma showed a significant advantage for CHOP in terms of disease-free survival and OS.[8]; [9][Level of evidence: 1iiA]
  3. Two other randomized trials of patients aged 70 years and older confirm the superiority of CHOP over other less toxic regimens in progression-free survival and OS.[8]; [9][Level of evidence: 1iiA]
  4. Although infusion regimens have been proposed, a randomized trial of infusional CHOP versus standard CHOP therapy showed no improvement in relapse-free survival or OS.[10][Level of evidence: 1iiA]
  5. A preliminary study using CHOP with or without etoposide for patients older than 60 years suggested improvement in EFS and OS for treatment delivered every 2 weeks versus the standard 3-week regimen.[11]
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