A phase I trial to assess the value of recombinant human granulocyte colony stimulating factor (r-MetHuG-CSF, filgrastim) in accelerating the dose rate of chemotherapy for intermediate and high-grade non-Hodgkin's lymphoma (NHL)
✍ Scribed by G. M. Smith; J. A. Child; M. H. Cullen; N. P. Bailey; C. M. Woodruffe; J. Fletcher; H. Earl; D. Barnard
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- English
- Weight
- 571 KB
- Volume
- 14
- Category
- Article
- ISSN
- 0278-0232
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✦ Synopsis
In a multi-centre phase I study we investigated the possibility of reducing the interval between courses of standard CHOP (cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m', vincristine 2 mgs day 1, and prednisolone 40mglm' days 1-8) from 21 days to 15 days and then 10 days using granulocyte colony stimulating factor (r-MetHuG-CSF (Amgen)-filgrastim) to accelerate neutrophil recovery. Patients received CHOP followed by G-CSF 5pg/kg S.C. from day 2 to the day before the next course (e.g. days 2-1 4 for the 15-day interval). A total of 28 patients with newly diagnosed intermediate grade or high grade NHL were studied. Four patients were studied at a 21-day interval, six patients were treated at a 15-day interval and subsequently six patients at a 10-day interval. Following analysis of this initial cohort, a further 12 patients were evaluated; four at the 15-day interval, and eight at the 10-day interval. No dose-limiting toxicity was seen in the four patients receiving 21-day CHOP. Dose-limiting toxicity was seen in 4/10 patients treated at the 15-day interval (M:F 7:3, median age 55.5, range 39-67 years). This consisted of infection in two patients, recurrent infection and debility in a third, and mucositis in a fourth. Seven patients experienced one or more infectious episodes requiring antibiotics (median number of episodes: 2, range 1 4 ) . Fourteen patients (M:F 4:3, median age 47.5, range 25-63 years) were treated at the 10-day interval. Dose-limiting toxicity was seen in six patients. This consisted of severe mucositis in three patients, neutropenia and thrombocytopenia on two separate occasions in one patient, and steroid-induced gastritis in two patients. Nine patients had one or more documented infections (median: 2, range 1-3) requiring antibiotics, of which six were severe (WHO grade 3 or 4). One patient died of Pneumocystis carinii (PCP) pneumonia. In summary, G-CSF (filgrastim) will facilitate the shortening of the dosage interval between cycles of CHOP chemotherapy due to accelerated hematological recovery. However, non-hematological toxicity due to the shorter dosage interval is increased and infective episodes are frequent. (13 1996 by John Wiley & Sons, Ltd. No. of Figures 3.