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  • 1
    ISSN: 1569-8041
    Keywords: cyclophosphamide ; dose-escalation ; epirubicin ; filgrastim ; G-CSF ; non-Hodgkin's lymphoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: To define a maximum tolerated dose (MTD) for the combination of epirubicin and cyclophosphamide with filgrastim (r-met-HuG-CSF) in patients with advanced solid tumors and non-Hodgkin's lymphoma (NHL). Patients and methods: Thirty-five patients with advanced solid tumors were enrolled in stages I and II. Twenty-one patients were treated in stage I in sequential cohorts of at least three patients at increasing dosage levels of cyclophosphamide and epirubicin, for up to six cycles every 21 days. At the completion of stage I, a MTD for epirubicin was established. Fourteen patients were treated in stage II, in cohorts of three or more. The epirubicin dose remained constant at the MTD dosage from stage I. Cyclophosphamide was further dose-escalated to establish its MTD. Twenty-one patients with previously untreated non-Hodgkin's lymphoma were treated in stage III with the MTD established in the prior stages. Results: The MTD in stage I was epirubicin 150 mg/m2 and cyclophosphamide 1500 mg/m2 with cumulative neutropenia as the dose-limiting toxicity (DLT). Cumulative thrombocytopenia prevented further dose-escalation of cyclophosphamide in stage II. The stage III regimen consisted of six, 21-day cycles of epirubicin 150 mg/m2, cyclophosphamide 1500 mg/m2, vincristine 2 mg, and prednisolone 100 mg for five days with filgrastim support. Nineteen of twenty-one patients (90%) completed six cycles of treatment, eight (38%) without dose reduction. Common toxicity criteria (CTC) grade 4 neutropenia (neutrophil nadir 〈0.5 × 109/l) was documented in 85 of 118 cycles (72%). Neutropenic fever was documented in 17 of 21 patients (81%) on at least one occasion. Severe thrombocytopenia (〈25 × 109/l) was seen in fourteen of 118 cycles (12%) and increased with cycle number. There was no significant non-hematological toxicity. Conclusion: Significant dose-escalation of epirubicin and cyclophosphamide was possible with filgrastim support. The MTD achieved was approximately double that of standard-dose therapy. This study forms the basis of an ongoing randomized study evaluating dose-intensification in intermediate grade NHL.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1569-8041
    Keywords: chemotherapy ; dose intensification ; long-term survival ; MACOP-B ; non-Hodgkin's lymphoma ; randomized trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: The initial publication of the results of the Australianand New Zealand Lymphoma Group (ANZLG) randomized controlled trial comparingMACOP-B and CHOP in patients with intermediate-grade non-Hodgkin's lymphoma(NHL) showed equivalent complete response rates, time to treatment failure,and survival. Here we report the long-term follow-up of the 236 patientsentered on that study to determine if there were any long-term advantages ordisadvantages associated with MACOP-B. Patients and methods: Two hundred thirty-six eligible patients wererandomized between October 1986 and June 1991. The median duration offollow-up has been extended from 3.2 years in our previous publication to 6.5years. Results: As previously reported, the complete response (CR) rate forMACOP-B and CHOP chemotherapy was 51% and 59%, respectively. Theestimated failure-free survival rate for MACOP-B and CHOP patients was42% and 30%, respectively, at 5 years (P = 0.045) and37% and 25%, respectively, at 8 years (P = 0.057). Theestimated overall survival rate at 5 years was 54% for MACOP-B and41% for CHOP patients (P = 0.035) and at 8 years was 45%and 36%, respectively (P = 0.16). Conclusion: With this extended follow-up, we have shown a long-termsurvival advantage for MACOP-B chemotherapy over standard CHOP inpatients with intermediate-grade non-Hodgkin's lymphoma.
    Type of Medium: Electronic Resource
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