Phase I study of weekly high-dose cisplatin combined with long-term oral etoposide in advanced solid tumors.
BACKGROUND
In a previous phase I study we showed that single-agent cisplatin can be given weekly for six weeks at a dose of 80 mg/m2/wk. It has been suggested that etoposide has synergistic activity with cisplatin and the drug can be given orally continuously. We therefore performed a phase I study with weekly cisplatin combined with oral etoposide.


METHODS
Nineteen patients with metastases of a solid tumor were entered in the study. Cisplatin was administered in hypertonic saline (NaCl 3%). Etoposide was administered as 50-mg capsules.


RESULTS
The starting dose was cisplatin weekly at a dose of 70 mg/m2 for six weeks combined with daily oral etoposide at a dose of 50 mg. At the maximum tolerable dose of cisplatin 75 mg/m2/wk and etoposide 50 mg/m2 daily, leukocytopenia and thrombocytopenia were dose-limiting toxic effects which resulted in frequent treatment delays. Other toxicities were mild. Finally, a dose of cisplatin 70 mg/m2/wk weeks 1-2-3 and weeks 5-6-7 in combination with etoposide 50 mg orally days 1-15 and days 29-43 combined a high median cisplatin dose intensity of 52.5 mg/m2/wk with a good patient tolerance.


CONCLUSIONS
It is feasible to administer frequently dosed cisplatin in combination with oral etoposide. Leukocytopenia and thrombocytopenia are dose-limiting toxicities. The schedule will be explored further in phase II studies.
Planting
A S
AS
Department of Medical Oncology, Rotterdam Cancer Institute/Daniel den Hoed Kliniek, The Netherlands.
van der Burg
M E
ME
de Boer-Dennert
M
M
Stoter
G
G
Verweij
J
J
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001855:Bone Marrow Diseases / Q000139:chemically induced; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy; D012074:Remission Induction; D016879:Salvage Therapy; D016896:Treatment Outcome
D005047:Etoposide; D002945:Cisplatin