, comparisons between treatment groups were performed for the elderly subset. In the one study (etoposide in combination with cyclophosphamide and vincristine compared with cyclophosphamide and vincristine or cyclophosphamide, vincristine, and doxorubicin) where age was a significant prognostic factor for survival, a survival benefit for elderly patients was observed for the etoposide regimen compared with the control regimens. No differences in myelosuppression were seen between elderly and younger patients in these studies except for an increased frequency of WHO Grade III or IV leukopenia among elderly patients in a study of etoposide phosphate or etoposide in combination with cisplatin. Elderly patients in this study also had more anorexia, mucositis, dehydration, somnolence, and elevated BUN levels than younger patients.
In five single-agent studies of etoposide phosphate in patients with a variety of tumor types, 34% of patients were aged 65 years or more. WHO Grade III or IV leukopenia, granulocytopenia, and asthenia were more frequent among elderly patients.
Postmarketing experience also suggests that elderly patients may be more sensitive to some of the known adverse effects of etoposide, including myelosuppression, gastrointestinal effects, infectious complications, and alopecia.
Although some minor differences in pharmacokinetic parameters between elderly and non-elderly patients have been observed, these differences were not considered clinically significant.
Etoposide and its metabolites are known to be substantially excreted by the kidney, and the risk of adverse reactions to Etopophos may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function (see PRECAUTIONS: Renal Impairment, for recommended dosing adjustments in patients with renal impairment).
Adverse Reactions
Etopophos has been found to be well tolerated as a single agent in clinical studies involving 206 patients with a wide variety of malignancies, and in combination with cisplatin in 60 patients with small cell lung cancer. The most frequent clinically significant adverse experiences were leukopenia and neutropenia.
The incidences of adverse experiences in the table that follows are derived from studies in which Etopophos was administered as a single agent. A total of 98 patients received total doses at or above 450 mg/m2 on a 5 consecutive day or day 1, 3, and 5 schedule during the first course of therapy.
Summary of Adverse Events Reported With Single-Agent Etopophos Following Course 1 at Total Five Day Doses of ≥450 mg/m2 Percent of Patients
Hematologic toxicity
Leukopenia <4000/mm3 91
<1000/mm3 17
Neutropenia <2000/mm3 88
<500/mm3 37
Thrombocytopenia <100,000/mm3 23
<50,000/mm3 9
Anemia <11 g/dL 72
<8 g/dL 19
Gastrointestinal toxicity
Nausea and/or vomiting 37
Anorexia 16
Mucositis 11
Constipation 8
Abdominal Pain 7
Diarrhea 6
Taste Alteration 6
Asthenia/Malaise 39
Alopecia 33
Chills and/or Fever 24
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