A PROSPECTIVE PHASE I II STUDY OF INTRAARTERIAL CHEMOTHERAPY AND ESCALATING DOSES OF RADIATION-THERAPY FOR SURGICALLY UNRESECTABLE CARCINOMA CONFINED TO THE LIVER/

Purpose: At Fox Chase Cancer Center intra-arterial 5-fluorouracil (5-F U), adriamycin and cisplatin and concurrent hepatic irradiation were s tudied in a prospective Phase I/II study in patients with biopsy prove n inoperable invasive cancer confined to the liver. The purpose of thi s trial was to employ an escalating dose schedule of radiation to dete rmine the feasibility, toxicity and efficacy of combination intra-arte rial chemotherapy and external beam radiation from 0 to 21 Gy. Methods and Materials: Patients received hepatic intra-arterial chemotherapy consisting of 5-FU 1000 mg/m(2)/day, 96 hour infusion, adriamycin 5 mg /m(2)/day bolus for four days and cisplatin 75 mg/m(2) day 1 concomita nt with involved field radiation at 300 cGy/day, Total radiation dose ranged from 0 - 2100 cGy as determined by a dose escalation schema of 0, 1200, 1500, 2100 cGy with a minimum of three patients per dose grou p. The chemotherapy regime was cycled every 28 days. Patients were req uired to have an ECOG performance status of less than or equal to 2 an d measurable disease. Results: Between 2/91 and 11/94, 17 patients wer e entered. All patients had > 75% of the whole liver irradiated and 6 (35%) had the entire liver treated. Only one patient, treated to 1800 cGy had greater than or equal to Grade 3 hepatic toxicity (Grade 3, el evated SGOT), Hematologic toxicity (greater than or equal to Grade 3) was observed as leukopenia in 12 patients (71%), granulocytopenia in 8 patients (47%), thrombocytopenia in 5 patients (29%), and anemia in 3 patients (18%). There were no treatment-related deaths, No significan t diarrhea or nausea/vomiting was observed. Thirteen patients were eva luable for response. Four of 13 (31%) evaluable patients experienced p artial response as defined by a greater than or equal to 50% reduction in CT scan measured tumor volume. Six patients (46%) achieved disease stabilization while only 3 patients progressed on treatment. Due to t he study design, the trial was terminated prior to determining the max imum tolerated radiation dose, Conclusion: At least 75% of the liver c an be irradiated to 2100 cGy with concomitant hepatic intra-arterial i nfusion of 5-FU, adriamycin and cisplatin without significant hepatic toxicity, and suggests that dose intensification with colony stimulati ng factor support may provide avenues for effective therapies in patie nts with unresectable cancers confined to the liver.