IEVM chemotherapy with rhGM-CSF support for aggressive non-Hodgkin's lymphomas: a pilot study.
Modern combination chemotherapy cures about one third of patients with non-Hodgkin's lymphomas (NHL) [3]. Attempts to increase this proportion by more intensive chemotherapeutic regimens have failed so far in randomized trials [4, 5]. Dose intensity has been reported to be important for cure [8]--a factor which can be enhanced by hematopoietic growth factors--but addition of recombinant human granulocyte colony-stimulating factor (rhG-CSF) to intensive chemotherapy did not improve response on survival in a controlled study published recently [10]. Therefore, we tried to design a regimen which might be more appropriate for combination with growth factors, using pulse chemotherapy rather than continuous treatment and employing drugs of low stem-cell toxicity. Ifosfamide (Ifo) appeared to be ideal because it is effective even in some resistant cases [1] and might act synergistically with anthracyclines by reducing intracellular glutathione levels [9]. Epirubicin (Epi) was favored because of its low hemato- and cardiotoxicity [2]. These drugs, together with etoposide (VP-16) had been found to be very effective in relapsed cases [7]. Methotrexate (Mtx) was added because it penetrates the spinal fluid. Moreover, we chose granulocyte/macrophage colony-stimulating factor (rhGM-CSF) as an adjunct cytokine because this not only enhances neutrophil regeneration [6] but might also have antitumor effects, as suggested by an uncontrolled study in sarcomas [11]. This report summarizes our experiences regarding feasibility, toxicity, and responses with this new regimen obtained in a pilot study.
Walther
J
J
Medical Department III, Klinikum Grosshadern, Munich University, Germany.
Wilmanns
W
W
Gerhartz
H H
HH
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D010865:Pilot Projects; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use
D011994:Recombinant Proteins; D015251:Epirubicin; D005047:Etoposide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007069:Ifosfamide; D008727:Methotrexate