title: Hyperfractionated radiotherapy and paclitaxel for locally advanced/unresectable pancreatic cancer.
abstract: OBJECTIVE
  To determine prospectively the maximal tolerated dose and potential antitumor activity of weekly paclitaxel with concurrent hyperfractionated radiotherapy in patients with locally advanced and/or unresectable pancreatic cancer.
  
  
  METHODS
  We embarked on Phase I-II study of hyperfractionated radiotherapy using a concomitant in-field boost to a total dose of 63.80 Gy in 6 weeks at 1.1 Gy/fraction. Paclitaxel was administered weekly on Days 1, 8, 15, 22, 29, and 36 as a 3-h infusion. Paclitaxel doses were escalated from 20 mg/m(2)/wk to 70 mg/m(2)/wk. Twenty patients were studied, 14 women and 6 men (mean age 64 years). Some patients presented with one or more symptoms. Obstructive jaundice was the main presenting symptom in 10 patients and epigastric pain in 14. All patients had unresectable histologically proven adenocarcinoma of the pancreas (15 head, 4 body, and 1 tail). Reasons for unresectability were involvement of the portal vein, and/or superior mesenteric artery (n = 14), paraaortic nodes (n = 8), and medically inoperable (n = 1). Fourteen patients underwent a biliary bypass procedure before treatment (four endoscopic stenting, five choledochojejunostomy, and five cholecystojejunostomy). The follow-up period ranged from 14 to 66 months (median 44).
  
  
  RESULTS
  The dose-limiting toxicity was observed at 70 mg/m(2)/wk. Grade IV Radiation Therapy Oncology Group late GI toxicity was seen in 1 patient in the form of duodenal stricture and hemorrhage. Grade II gastrointestinal adverse effects occurred in 13 patients and Grade 3 in 1 patient. No neurologic morbidity was encountered. Eight patients required cytokine support for Grade 2 and 3 neutropenia. The treatment course was delivered within the planned time in 80% of the patients. Complete relief of pain occurred in 10 of 14 patients. The CA 19-9 level was either stable or decreasing in 12 of 15 patients. Of 17 assessable patients, stable disease was seen in 10, regression in 2, a partial response in 3, and a complete response in 2.
  
  
  CONCLUSIONS
  The use of hyperfractionated radiotherapy to a dose of 63.80 Gy with concomitant weekly paclitaxel is tolerated. The maximal tolerated dose of paclitaxel for this study was 60 mg/m(2)/wk. The preliminary objective responses denote activity of the regimen. We recommend testing this regimen in larger scale studies.
authors.affiliation: Department of Radiation Oncology, New York Methodist Hospital, Weill Medical College, Brooklyn, NY 11215, USA. Hashamalla@aol.com
authors.forename: H
authors.initials: H
authors.lastname: Ashamalla
authors.forename: B
authors.initials: B
authors.lastname: Zaki
authors.forename: B
authors.initials: B
authors.lastname: Mokhtar
authors.forename: F
authors.initials: F
authors.lastname: Colella
authors.forename: H
authors.initials: H
authors.lastname: Selim
authors.forename: M
authors.initials: M
authors.lastname: Krishnamurthy
authors.forename: P
authors.initials: P
authors.lastname: Ross
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000532:radiotherapy*; D000368:Aged; D000369:Aged, 80 and over; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000209:etiology; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects*; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000532:radiotherapy*; D010349:Patient Compliance; D011446:Prospective Studies; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000009:adverse effects*; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D011838:Radiation-Sensitizing Agents; D017239:Paclitaxel