Chemotherapy in carcinomas of unknown primary site: A high-dose intensity policy

Background: Unknown primary tumors are highly malignant diseases which port end a dire prognosis. We designed a prospective high dose-intensity policy with the aim of improving the results obtained with conventional chemothera py. Patients and methods: Chemotherapy regimens were determined according to cl inical features. In patients younger than 61 years with an ECOG performance status of 0 or 1, poorly differentied adenocarcinoma or poorly differentia ted carcinoma, and no evidence of brain or bone marrow involvement (group A ), the treatment plan included four sequential high-dose courses with hemat opoietic progenitor cell and growth factor support. Peripheral blood progen itor cells were collected by apheresis as the leukocyte counts recovered fr om the nadir induced by the first cycle of chemotherapy (doxorubicin 75 mg/ m(2), cyclophosphamide 6000 mg/m(2)). Patients then received two cycles of etoposide (800 mg/m(2)) and carboplatin (900 mg/m(2)) separated by one cycl e of doxorubicin (75 mg/m(2)) and cyclophosphamide (3000 mg/m(2)). G-CSF (5 mu g/kg/d) was given until engraftment. It was planned that cycles would b e delivered every three weeks. The remaining patients (group B) received al ternative cycles of AC (doxorubicin 50 mg/m(2), cyclophosphamide 1000 mg/m( 2)) and EP (etoposide 300 mg/m(2), cisplatin 100 mg/m(2)). Cycles were give n at two-week intervals with GM-CSF support (5 mu g/kg/d) from day 4 to day 10. Patients without measurable lesions were included, since the major end point 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 meas urable lesions (42%; 95% confidence interval (95% CI): 22%-62%) achieved ma jor responses to chemotherapy, including one complete response. The duratio n of the overall median survival was 11 months. In group B, a major respons e was observed in 12 (39%; 95% CI: 28%-50%) of 31 patients with measurable lesions, including three complete responses. The overall median survival wa s 8 months. Hematological toxicities were noteworthy in both groups. Two to xic deaths occurred in group B. Conclusion: Using these doses and schedules of chemotherapy, a high-dose in tensity policy does not appear to improve the outcome of patients with carc inoma of unknown primary site. Alternative studies dealing with new drugs a re required.