title: Paclitaxel and concurrent radiation for locally advanced pancreatic carcinoma.
abstract: An effective local-regional therapy is needed for adenocarcinomas of the pancreas. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton NJ) may enhance the effect of radiation therapy. Paclitaxel synchronizes cells at G2/M, a relatively radiosensitive phase of the cell cycle. We have shown that response to paclitaxel and concurrent radiation (paclitaxel/RT) was not affected by p53 mutations in non-small cell lung cancer (NSCLC). This suggested that paclitaxel/RT was a rationale treatment approach for other malignancies which frequently harbor p53 mutations such as upper gastrointestinal malignancies. We have completed a phase I study of paclitaxel/RT for locally advanced pancreatic and gastric cancers. The maximum tolerated dose (MTD) of paclitaxel was 50 mg/m2/week for 6 weeks with abdominal radiation. The dose limiting toxicities were abdominal pain within the radiation field, nausea and anorexia. Twenty-five patients with locally advanced pancreatic cancer have now completed treatment at the phase II dose level of paclitaxel 50 mg/m2/week with 50 Gy concurrent RT. Thus far, the only grade 3/4 toxicities have been hypersensitivity reactions in 2 patients, asymptomatic grade 4 neutropenia in 3 patients, and non-neutropenic biliary sepsis in 1 patient. Of the first 22 assessable patients treated at the phase II study, 8 obtained a partial response (PR) for a preliminary response rate of 36%. These findings demonstrate that paclitaxel/RT is well tolerated with substantial activity for locally advanced pancreatic cancer.
authors.affiliation: Brown University Oncology Group and The Brown University School of Medicine, Providence, RI 02908, USA. hsafran@rihodp.edu
authors.forename: H
authors.initials: H
authors.lastname: Safran
authors.forename: W
authors.initials: W
authors.lastname: Cioffi
authors.forename: D
authors.initials: D
authors.lastname: Iannitti
authors.forename: A
authors.initials: A
authors.lastname: Mega
authors.forename: P
authors.initials: P
authors.lastname: Akerman
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D006801:Humans; D008875:Middle Aged; D017239:Paclitaxel / Q000009:adverse effects / Q000627:therapeutic use*; D010190:Pancreatic Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D011838:Radiation-Sensitizing Agents / Q000009:adverse effects / Q000627:therapeutic use; D013274:Stomach Neoplasms / Q000473:pathology / Q000532:radiotherapy; D016896:Treatment Outcome
chemical_list: D011838:Radiation-Sensitizing Agents; D017239:Paclitaxel