title: Addition of amifostine to the CHOP regimen in elderly patients with aggressive non-Hodgkin lymphoma: a phase II trial showing reduction in toxicity without altering long-term survival.
abstract: OBJECTIVE
  We report the 8-year follow-up of 34 patients aged ≥69 years old with NHL included in a phase IIb open-label randomized parallel groups study to evaluate the effectiveness of amifostine in preventing the toxicity of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP regime) .
  
  
  METHODS
  Patients were randomized to receive classical CHOP (cyclophosphamide 750 mg/m(2), doxorubicin 50 mg/m(2), vincristine 1.4 mg/m(2) [maximum 2 mg] on day 1 and prednisone 100 mg/day for 5 days) or CHOP plus amifostine (6 cycles of amifostine 910 mg/m(2) on day 1). Efficacy (time to progression, TTP; disease-free survival, DFS; overall survival, OS) and toxicity endpoints were evaluated.
  
  
  RESULTS
  Thirty-four patients were randomized to A-CHOP (n=18) or CHOP (n=16). Patients with A-CHOP vs CHOP had significantly lower toxicity; neutropenia grade 4 ocurred in 13/92 (13%) vs 23/85 (27%, P=0.007) cycles, febrile neutropenia in 3/92 A-CHOP (3%) vs 8/85 (10%, P=.056) CHOP cycles, hospitalization for toxicity in 4/92 (4%) A-CHOP vs 11/85 (13%, P=.05) CHOP cycles. Median hospitalization stay for toxicity was 5 days with A-CHOP vs 8 days with CHOP (P=.05). There were no significant differences at 8 years in TTP (A-CHOP, 48.9% vs CHOP, 36.3%; P=.65), DFS (A-CHOP, 72.9% vs CHOP 55.6%; P=.50) and OS (A-CHOP, 44.3% vs CHOP, 54.4%). There was no long-term toxicity of clinical interest. The only prognostic factor identified to 8 years was the International Prognostic Index (IPI low/low intermediate risk vs high intermediate/high risk; HR=2.98; CI 95%:1.01-8.77; P=.048).
  
  
  CONCLUSIONS
  These results show that amifostine can be added to the standard CHOP treatment schedule with less acute toxicity and without influencing the outcome.
authors.affiliation: Department of Medical Oncology, Instituto Nacional de Enfermedades Neoplásicas, Lima, Perú. hgomez@inen.sld.pe
authors.forename: Henry L
authors.initials: HL
authors.lastname: Gómez
authors.forename: César
authors.initials: C
authors.lastname: Samanéz
authors.forename: Frank
authors.initials: F
authors.lastname: Campana
authors.forename: Silvia P
authors.initials: SP
authors.lastname: Neciosup
authors.forename: Luis
authors.initials: L
authors.lastname: Vera
authors.forename: Luis
authors.initials: L
authors.lastname: Casanova
authors.forename: Jorge
authors.initials: J
authors.lastname: Leon
authors.forename: Claudio
authors.initials: C
authors.lastname: Flores
authors.forename: Fernando Hurtado
authors.initials: FH
authors.lastname: de Mendoza
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Casteñeda
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Pinto
authors.forename: Carlos S
authors.initials: CS
authors.lastname: Vallejos
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D004999:Amifostine / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007970:Leukopenia / Q000209:etiology; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D009503:Neutropenia / Q000209:etiology; D011241:Prednisone / Q000009:adverse effects / Q000627:therapeutic use; D011379:Prognosis; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D014750:Vincristine / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D011837:Radiation-Protective Agents; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D004999:Amifostine; D011241:Prednisone