RANDOMIZED STUDY OF ZORUBICIN VERSUS ZORUBICIN-CISPLATIN IN UNDIFFERENTIATED CARCINOMA OF THE NASOPHARYNX (UCNT)

Background. The most active chemotherapy regimens in UCNT were those c ombining anthracyclines (doxorubicin or epirubicin) and cisplatin. Our previous pilot study on 35 patients treated with the zorubicin-cispla tin combination with a RR of 67% and literature data about other anthr acyclines such as epirubicin achieving a response rate of over 50% wer e the basis of this randomized study comparing efficacy and toxicity o f the combination vs. zorubicin as monotherapy Patients and methods. A total of 80 patients entered the study. The diagnosis of UCNT was con firmed by two independent pathologists. All patients had their primary tumors in the nasopharynx. The patients were randomized in two groups : group A (zorubicin 325 mg/m(2), day 1), and group B (zorubicin 250 m g/m(2), day 1 and cisplatin 30 mg/m(2), days 2-5). The inter-cycle int erval was four weeks. The two groups were well balanced according to s ex, age, stage Ho and TNM stage. Results. Group A: 40 patients include d, 34/40 evaluable for activity. Activity on evaluable patient basis: CR 4/34 (11.75%), PR 4/34, SD 14/34, PD 12/34, response rate 8/34 (23. 5%); response rate on intent to treat basis 8/40 (20%). Toxicity: gran ulocytopenia grade 3-4 6/40, thrombocytopenia grade 3-4 2/40, no febri le neutropenias? nausea/vomiting any grade 3/40, cardiac toxicity any grade (rhythm) 3/40 other toxicities minor or absent. Group B: 40 pati ents included, 36/40 evaluable for activity. Activity on evaluable pat ient basis: CR 10/36 (27.78%), PR 17/36, SD 3/36, PD 6/36, response ra te 27/36 (75%); response rate on intent to treat basis 27/40 (67.5%). Toxicity: granulocytopenia grade 3-4 10/40, thrombocytopenia grade 3-4 8/40, two febrile neutropenias, nausea/vomiting any grade 13/40, othe r toxicities mild or absent. Of the group of patients achieving a CR, four relapsed following 7, 11, 22 and 23 months, one was lost to follo w-up, one died after six months from fulminant hepatitis B and eight a re in complete remission lasting for 30+ to 66+ months. Following CR a chievement none received any consolidation radiotherapy, and the proje cted five years of freedom from relapse for complete responders is abo ut 60%. Conclusion. Zorubicin is an effective drug in UCNT and its com bination with cisplatin has a significant activity and an acceptable t oxicity.