title: Chemoradiotherapy in the treatment of regional pancreatic carcinoma: a phase II study.
abstract: In locally advanced pancreatic cancer, the utilization of chemotherapy and radiotherapy is increasing, although in view of the reported long-term results of several contemporary trials, further improvements are certainly needed. Encouraging results using the combination of cisplatin, cytarabine, caffeine, and continuous infusion (CI) 5-fluorouracil (5-FU) (PACE) for the treatment of advanced pancreatic carcinoma prompted a phase II study using PACE followed by external beam radiotherapy with CI of 5-FU (PACE-RT) for localized disease. Forty-one patients were treated with PACE-RT as adjuvant therapy after surgical resection (21 patients), or as primary therapy for locally advanced, unresectable disease (20 patients), with reevaluation for resection after completion of treatment. PACE consisted of cisplatin 100 mg/m2 IV on day 1, cytarabine 2 g/m2 IV every 12 hours x 2 doses, and caffeine 400 mg/m2 subcutaneously after each cytarabine dose; and days 3 to 21, 5-FU 250 mg/m2/d given by CI. Cycles were repeated every 28 days. After 2 cycles of PACE, radiation therapy was given concurrently with 5-FU at 200 mg/m2/d. In the adjuvant setting, the tumor bed and the draining lymph node basin received 50.4 Gy and 45 Gy, respectively. In the neoadjuvant setting, the primary and regional lymph nodes were to receive 39.6 Gy followed by a neutron boost of 8 NGy to the gross tumor volume. Photon therapy was delivered at 1.8 Gy per fraction and neutron therapy at 0.8 NGy per fraction, 5 days a week. All patients were evaluable for toxicity and survival. The most common toxicity was myelosuppression, with grade III to IV neutropenia occurring in 59% of the patients. The median survival times in the locally advanced and adjuvant patients were 13.4 and 18.1 months, with 1-year survival rates of 52% and 65%, respectively. Nine of 20 patients receiving PACE-RT for unresectable carcinoma had sufficient tumor regression to meet clinical criteria for exploration; three were resected with curative intent. The survival of these three patients undergoing resection after neo-adjuvant therapy was 22.4, 24.3 and 40 months. The treatment program was active, but only moderately well tolerated. Modification of this regimen with newer, less toxic drugs may provide better results and reduced toxicity.
authors.affiliation: Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: Sana
authors.initials: S
authors.lastname: Al-Sukhun
authors.forename: Mark M
authors.initials: MM
authors.lastname: Zalupski
authors.forename: Edgar
authors.initials: E
authors.lastname: Ben-Josef
authors.forename: Vainutis K
authors.initials: VK
authors.lastname: Vaitkevicius
authors.forename: Philip A
authors.initials: PA
authors.lastname: Philip
authors.forename: Renate
authors.initials: R
authors.lastname: Soulen
authors.forename: Donald
authors.initials: D
authors.lastname: Weaver
authors.forename: Volkan
authors.initials: V
authors.lastname: Adsay
authors.forename: Lance K
authors.initials: LK
authors.lastname: Heilbrun
authors.forename: Kenneth
authors.initials: K
authors.lastname: Levin
authors.forename: Jeffery D
authors.initials: JD
authors.lastname: Forman
authors.forename: Anthony F
authors.initials: AF
authors.lastname: Shields
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000532:radiotherapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002110:Caffeine / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D016019:Survival Analysis
chemical_list: D003561:Cytarabine; D002110:Caffeine; D002945:Cisplatin; D005472:Fluorouracil