PALSADIUM-103 - A NEW RADIOACTIVE SOURCE IN THE TREATMENT OF UNRESECTABLE CARCINOMA OF THE PANCREAS - A PHASE I-II STUDY

Palladium-103 (Pd-103) is introduced in brachytherapy procedures becau se of its favorable physical properties, including its low energy, rap id dose fall-off, short half-life, and total cumulative dose delivery at a higher dose rate than iodine-125 (I-125) isotope. Intraoperative brachytherapy using I-125 pellets was reported to provide significant palliation and meaningful prolongation of life in highly selected pati ents with unresectable carcinoma of the pancreas. After considering so me of the advantages of Pd-103 over I-125, we designed a phase I-II cl inical trial to assess the feasibility of intraoperative Pd-103 in unr esectable carcinoma of the pancreas to study the related morbidity whe n combined with chemotherapy and external beam radiation, and to evalu ate the impact on palliation and local control rates. Between December 1989 and December 1993, 15 patients with biopsy-proven unresectable a denocarcinoma of the pancreas were treated with interstitial Pd-103 im plants during laparotomy. In 13 patients the lesion was located in the head of the pancreas, in one patient in the uncinate process, and in one patient in the body of the pancreas. The stage distribution was as follows: T1 = 2; T2 = 6, and T3 = 7. In addition, all patients underw ent biliary and gastric bypass. The mean number of Pd-103 pellets was 45; the mean total activity to obtain a matched peripheral dose (MPD) of 11,000 cGy was 68.9 mCi. The mean tumor volume encompassing the MPD was 16.5 cc. All patients received postoperative external beam radiat ion (4,500 cGy over 41/2 weeks) and chemotherapy (5-fluorouracil and m itomycin C). This combined treatment, consisting of intraoperative bra chytherapy using Pd-103 and postoperative external beam radiation with chemotherapy, was well tolerated in all patients. There were no treat ment-related mortalities, and no serious complications, such as bleedi ng or fistula formation. Pain relief was obtained within 3-6 weeks in 10 out of 12 patients presenting with pain. Survival ranged from 6 to 24 months (median 10 months). The study suggests that Pd-103 can be co nsidered an alternative to I-125 for interstitial brachytherapy for un resectable carcinoma of the pancreas. Symptom relief appeared to occur faster and complications are significantly less. However, this study did not show any improvement in the median survival rate over I-125 du e to the advanced stage cancer in the majority of patients in the stud y. (C) 1996 Wiley-Liss, Inc.