RTOG Protocol No: 9812	Protocol Status:
	Opened:	November 9, 1998
	Closed:	March 1, 2000

Title:

A Phase II Study of External Irradiation (50.4 Gy) and Weekly Paclitaxel (Taxol) for Non-Metastatic, Unresectable Pancreatic Cancer

Patient Population:
- Pathologically confirmed unresectable non-metastatic adenocarcinoma of the pancreas;
- All malignant disease must be encompassable within a single irradiation field (15 x 15 cm maximum);
- Radiographically assessable;
- No prior irradiation to the planned field;
- KPS > 60; Age > 18;
- Granulocytes > 1800/ul; platelets > 100,000; bilirubin < 2 mg/dL;
- Creatinine < 3.0 mg % or creatinine clearance > 40 ml/min.;
- Oral intake > 1500 calories/day;
- Signed study-specific consent form.

Objectives:

1. To determine the one-year and median survival rates after PXRT.

2. To determine the response rate of PXRT in unresectable pancreatic cancer in a multi-center trial.

3. To evaluate the acute and late treatment morbidity of paclitaxel in a multi-institutional setting.

4. To correlate p53 status with treatment response to PXRT.

Schema:

R
E
G
I	Radiation Therapy:	50.4 Gy / 28 fractions (1.8 Gy per fraction) once a day in 5.5 weeks.
S
T	Chemotherapy:	Paclitaxel 50 mg/m2 given on days 1, 8, 15, 22, 29, and 36.
E
R

Study Chairs:	Tyvin Rich, M.D. (Radiation Oncology)	Total Patients Entered: 122
	Howard Safran, M.D. (Medical Oncology)
	Harold Wanebo, M.D. (Surgical Oncology)

Reference: Rich T, et al: A Phase II Study of External Irradiation And Weekly Paclitaxel for Non-Metastatic, Unresectable Pancreatic Cancer: A Preliminary Report of RTOG Protocol 98-12. Proc of Am Soc Ther Rad Oncol (ASTRO), San Francisco, CA. Int J Radiat Oncol Biol Phys 51:29-30, 2001.

Purpose: A new approach for the management of unresectable cancer of the pancreas tested the combination of paclitaxel and external beam irradiation in an effort to improve palliation and extend life with minimal toxicity.

Materials and Methods: One hundred twenty-two patients were entered into a multi-centered protocol. Nine patients were either ineligible, cancelled, or had incomplete data available thus providing 113 for analysis. Unresectable cancer was based on imaging studies (CT or MRI), all had histologic proof of adenocarcinoma, and none had evidence of metastatic disease or peritoneal seeding. Patients with residual disease after resection (R-1,2) were eligible as long as radiographically measurable disease was present. Image guided radiotherapy treatment consisted of 50.4 Gy in 28 fractions over 5.5 weeks with co-planar anterior/posterior and lateral ports. The initial fields included the primary tumor plus the regional peri-pancreatic, celiac, and porta hepatis lymph nodes. A cone down field was used for the last three fractions to encompass the gross tumor volume with a 1 to 2 cm margin. Paclitaxel was administered weekly during the course of irradiation in a dosage of 50 mg/m² as a three hour infusion.

Results: The median age was 63, and 53% were female. The KPS status was > 80 in 81%. Seventy-nine percent were classified T 3 or 4; 24% had N1 disease. The primary tumor was located in the pancreatic head in 65%. Eighty-five percent received all six cycles of paclitaxel per protocol while 91% received irradiation with acceptable protocol variation. Field placement, total dose, fractionation, and overall treatment time were given per protocol in > 90%. Acute toxicity (worst per patient) occurred in 33% with grade 3 (43% of these were asymptomatic neutropenia), 4% with grade 4, and one patient died of infection during the fourth cycle of chemotherapy (grade 5). The median follow-up time for living patients is 280 days (range 36 to 529). The median survival is 11.9 months (95% confidence interval 10.3, 14.0) with an estimated 1-year survival of 48 %.

Conclusion: External irradiation plus concurrent weekly paclitaxel is well tolerated when given with large radiotherapy fields covering the primary cancer and surrounding lymphatics. A median survival of one year is better than historical results achieved with irradiation and fluoropyrimidines (5-FU). These data provide a basis for a new RTOG trial using paclitaxel and irradiation combined with a second radiation sensitizer, gemcitabine.