The Efficacy of PEEL Chemotherapy and Identification of Favoranble Subgroups in Patients with Carcinomas of Unknown Primary Origin

Choi, Byung Kook; Yuh, Young Jin; Yang, Jeong Hoon; Kim, Seong Bae; Park, Yeon Hee; Kim, Bong Seog; Ryoo, Baek Yeo; Kim, Tae You; Im, Young Hyuck; Kang, Yoon Koo

Abstract

PURPOSE: In order to evaluate the efficacy of PEFL (cisplatin, etoposide, 5-fluorouracil and leucovorin) chemotherapy and to identify favorable subsets, we conducted a phase II trial of PEFL regimen for patients with carcinomas of unknown primary origin (CUPO).
MATERIALS AND METHODS
A total of 38 patients was enrolled in this study between May 1995 and September 1997. CUPO was defined as the presence of metastatic cancer documented in the absence of an identifiable primary site. All entered patients were treated with PEFL combination chemotherapy (cisplatin 20 mg/m(2)/day i.v, days 1-5, etoposide 100 mg/m(2)/day i.v. days 1, 3 & 5, 5-fluorouracil 800 mg/m(2)/day continuous infusion days 1-5, and leucovorin 20 mg/m(2)/day i.v, days 1-5; repeated every 4 weeks). The end points of this study were response and survival. To identify favorable subsets, univariate and multivariate analyses were perfonned.
RESULTS
Among 38 patients, 29 had measurable lesions. Three (11%) out of 27 evaluable patients had a complete response and 7 (26%) had a partial response (response rate 37%; 95% confidence interval 19~55%). The median survival of the total 38 enrolled patients was 9.1 (range; 1~21.9+) months. The median progression-free survival of the 27 evaluable patients was 5.3 (range 0~ 16.0) months. Among total 132 cycles of chemotherapy, leukopenia of grade II or more was observed in 15% and thrombocytopenia of grade I in 4%. There was no treatment-related death. Main non-hematologic toxicities were nausea/vomiting (79%), stomatitis (70%), and neurotoxicity (33%). The prognostic factor analyses identified 2 favorable subgroups; One was the patient group whose disease had poorly differentiated histology and presented in cervical lymph node. This group of patients had better response rate than other patients (response rate; 71% vs 25%, p=0.02). The other was the patient group who had normal tumor markers (CEA, CA 125 and CA 19-9). This group of patients had better survival than other patients(median survival; 14.8 vs 8.4 months, p=0.05).
CONCLUSION
PEFL chemotherapy seemed to be moderately active and tolerable in patients with CUPO. Among heterogenous patients with CUPO, the subset with cervical lymph node and poorly differentiated histology responded better to the chemotherapy and those with normal tumor markers tended toward longer survival.