Dose-escalation of CHOP in non-Hodgkin's lymphoma

A. Santoro, M. Balzarotti, C. Tondini, M. Zanini, R. Giardini, F. Latteri, I. Rampinelli, R. Bufalino

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Background: CHOP is considered to be the gold standard for patients with histologically aggressive non-Hodgkin's lymphoma both in limited and advanced stages. In order to determine the maximum tolerable dose of an intensified CHOP regimen, a dose-escalation study of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) in patients with non-Hodgkin's lymphoma (NHL) was started. Patients and methods: With an increased fixed dose of doxorubicin at 75 mg/m2 instead of 50 mg/m2 on day 1 and standard doses of vincristine (1.4 mg/m2 on day 1) and prednisone (100 mg day 1 through 5), cyclophosphamide dose was escalated by increments of 250 mg/m2 in consecutive cohorts of at least three patients starting from 1000 mg/m2. Granulocyte-colony stimulating factor (G-CSF) support was added to the regimen starting from the dose-level inducing grade 4 neutropenia lasting more than five days in two patients. Dose limiting toxicity was defined as either the dose inducing grade 4 neutropenia lasting more than seven days despite the use of G-CSF, or grade 3-4 thrombocytopenia lasting more than seven days, or any grade 4 non-hematological toxicity other than alopecia. The dose-level below the one inducing dose-limiting toxicity was defined as maximum tolerable dose. All patients were treated on an outpatient basis. Dose-intensity parameters for single agent doxorubicin and cyclophosphamide as well as for the whole regimen were evaluated. Results: Eighty-seven patients are evaluable over a four-year study period. At 1750 mg/m2 dose- level, G-CSF was added to the regimen according to described criteria. At the cyclophosphamide dose of 3000 mg/m2 dose-limiting hematological toxicity occurred in two patients, with one grade 4 thrombocytopenia and neutropenia and one grade 4 neutropenia lasting more than seven days. Thus, cyclophosphamide dose of 2750 mg/m2 was defined as maximum tolerable dose. Conclusions: CHOP intensification of approximately 1.8 times that of the standard regimen is feasible and safely administered on an outpatient basis with G-CSF support. Further investigation on the role of dose-intensity in the outcome of NHL should focus on the comparison of intensified CHOP regimen and standard CHOP or high-dose chemotherapy.

Original languageEnglish
Pages (from-to)519-525
Number of pages7
JournalAnnals of Oncology
Issue number5
Publication statusPublished - 1999


  • CHOP chemotherapy
  • Dose-intensity
  • Non-Hodgkin's lymphomas

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Hematology


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