Chemotherapy in carcinomas of unknown primary site: a high-dose intensity policy.
BACKGROUND
Unknown primary tumors are highly malignant diseases which portend a dire prognosis. We designed a prospective high dose-intensity policy with the aim of improving the results obtained with conventional chemotherapy.


METHODS
Chemotherapy regimens were determined according to clinical features. In patients younger than 61 years with an ECOG performance status of 0 or 1, poorly differentiated adenocarcinoma or poorly differentiated carcinoma, and no evidence of brain or bone marrow involvement (group A), the treatment plan included four sequential high-dose courses with hematopoietic progenitor cell and growth factor support. Peripheral blood progenitor cells were collected by apheresis as the leukocyte counts recovered from the nadir induced by the first cycle of chemotherapy (doxorubicin 75 mg/m2, cyclophosphamide 6000 mg/m2). Patients then received two cycles of etoposide (800 mg/m2) and carboplatin (900 mg/m2) separated by one cycle of doxorubicin (75 mg/m2) and cyclophosphamide (3000 mg/m2). G-CSF (5 micrograms/kg/d) was given until engraftment. It was planned that cycles would be delivered every three weeks. The remaining patients (group B) received alternative cycles of AC (doxorubicin 50 mg/m2, cyclophosphamide 1000 mg/m2) and EP (etoposide 300 mg/m2, cisplatin 100 mg/m2). Cycles were given at two-week intervals with GM-CSF support (5 micrograms/kg/d) from day 4 to day 10. Patients without measurable lesions were included, since the major endpoint was survival.


RESULTS
Sixty patients entered the study. Twenty patients were assigned to group A and 40 patients to group B. In group A, 5 of 12 patients with measurable lesions (42%; 95% confidence interval (95% CI): 22%-62%) achieved major responses to chemotherapy, including one complete response. The duration of the overall median survival was 11 months. In group B, a major response was observed in 12 (39%; 95% CI: 28%-50%) of 31 patients with measurable lesions, including three complete responses. The overall median survival was 8 months. Hematological toxicities were noteworthy in both groups. Two toxic deaths occurred in group B.


CONCLUSIONS
Using these doses and schedules of chemotherapy, a high-dose intensity policy does not appear to improve the outcome of patients with carcinoma of unknown primary site. Alternative studies dealing with new drugs are required.
Culine
S
S
Centre Régional de Lutte contre le Cancer Val d'Aurelle, Montpellier, France. StCuline@valdorel.fnclcc.fr
Fabbro
M
M
Ychou
M
M
Romieu
G
G
Cupissol
D
D
Pujol
H
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009382:Neoplasms, Unknown Primary / Q000188:drug therapy* / Q000401:mortality; D011446:Prospective Studies; D015996:Survival Rate