Alternative bimonthly cycles of doxorubicin, cyclophosphamide, and etoposide, cisplatin with hematopoietic growth factor support in patients with carcinoma of unknown primary site.
BACKGROUND
Because carcinomas of unknown primary origin are highly malignant tumors with a bad prognosis (median survival, 6-12 months) and no current optimal therapy, the authors designed a prospective dose-dense chemotherapy regimen with the objective of improving the results observed in patients who receive conventional treatment.


METHODS
Eighty-two patients received alternative bimonthly cycles of doxorubicin 50 mg/m(2) with cyclophosphamide 1000 mg/m(2) (AC) and etoposide 300 mg/m(2) with cisplatin 100 mg/m(2) (EP). Cycles were given at 2-week intervals with granulocyte-macrophage-stimulating factor support (5 microg/kg per day) from Day 4 to Day 10. Patients without measurable lesions were included, because the major end point was survival.


RESULTS
The median number of alternative cycles of AC and EP was 4 cycles (range, 1-12 cycles). An objective response was observed in 24 of 62 patients (39%; 95% confidence interval, 30-48%) with measurable lesions, including 6 patients who achieved a complete response. Among 20 patients with nonmeasurable disease, 9 patients (45%) had no evidence of progressive disease at the end of chemotherapy. The overall median survival of 82 patients was 10 months, with 5 patients surviving clinically disease free at 17 months, 29 months, 45 months, 64 months, and 70 months after the end of treatment. Myelosuppression was the most common toxicity. Two toxic deaths occurred.


CONCLUSIONS
Using these doses and schedules, a dose-dense chemotherapy regimen did not appear to improve the outcome of patients with carcinoma of unknown primary site. Alternative studies dealing with news drugs will be required.
Culine
Stéphane
S
Centre Régional de Lutte Contre le Cancer Val d'Aurelle, Montpellier, France. stculine@valdorelfnclcc.fr
Fabbro
Michel
M
Ychou
Marc
M
Romieu
Gilles
G
Cupissol
Didier
D
Pinguet
Frédéric
F
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin; D003520:Cyclophosphamide; D018572:Disease-Free Survival; D004317:Doxorubicin; D004334:Drug Administration Schedule; D005047:Etoposide; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009382:Neoplasms, Unknown Primary / Q000188:drug therapy* / Q000473:pathology; D011446:Prospective Studies; D016896:Treatment Outcome
D005047:Etoposide; D004317:Doxorubicin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide; D002945:Cisplatin