Pancreatic Cancer Update

Summarized by Robert W. Griffith, MD
April 8, 2004

Introduction

Cancer of the pancreas is usually rapidly fatal - the 5-year survival rate is reported to be between 1% and 4%. By the time symptoms develop, it's often too late for fully successful surgery; however, the risks associated with this major procedure have fallen recently, so that only about 1% of patients die due to the operation.

It's become increasingly important to select the best postoperative therapy for these patients. The choice lies between chemotherapy and chemoradiotherapy. (Not doing anything after surgery is not a good option, from the survival viewpoint.)

A study reported in the New England Journal of Medicine has examined the outcomes after these two types of treatment.

What was done

289 patients who had their pancreatic cancer removed by surgery were randomly assigned to one of four treatment groups: 1. chemoradiotherapy (where a chemo drug is given initially to sensitize the cells to radiation); 2. chemotherapy alone; 3. chemoradiotherapy plus chemotherapy; 4. observation (no drugs or radiation).

Chemoradiotherapy consisted of a 20-Gy dose of radiation¹ given as 2-Gy a day for 10 days, plus an i.v. injection of fluorouracil on the first 3 days, and again after a break of 2 weeks. Chemotherapy was an i.v. dose of leucovorin, followed by fluorouracil on 5 consecutive days every month, for 6 months. Combination therapy was chemoradiotherapy first, followed by chemotherapy.

Patients were followed carefully for adverse effects of treatment, the recurrence of tumor, and quality-of-life assessments. In determining the benefits of different treatments, chemoradiotherapy (groups 1 & 3) was compared with no chemoradiotherapy (groups 2 & 4), and chemotherapy (groups 2 & 3) with no chemotherapy (groups 1 & 4).

What was found

A total of 289 patients from 53 European hospitals were entered into this study - just over 70 per treatment group. Quite a few patients didn't complete their treatment protocols - as many as one in three of the group assigned to receive chemoradiotherapy followed by chemotherapy. This was presumably due to the side effects produced - chiefly hematological changes, stomatitis (mouth infections), and diarrhea. However, there were no significant differences in quality-of-life scores between those receiving chemoradiotherapy, chemotherapy, and the combination of both.

The analysis of survival was based on 237 deaths in these patients (82%) after an average of 4 years (47 months). Based on the rate of deaths in each group over the study period, the 5-year survival rates were calculated.

The 5-year survival rate was 10% for those given chemoradiotherapy, compared to 20% for those who did not receive chemoradiotherapy. Chemoradiotherapy therefore had a harmful effect on survival.

On the other hand, chemotherapy proved beneficial; the 5-year survival rate for those receiving chemotherapy was 21%, compared to 8% in those not given chemotherapy.

Expressed differently, the results showed an average (median) survival of 15.9 months for chemoradiotherapy, 17.9 months for those not receiving chemoradiotherapy, 20.1 months for those receiving chemotherapy, and 15.5 months for those not receiving chemotherapy. Clearly, chemotherapy was the best option in this study, although the gain in average survival time was small.

What does this mean?

The design of this study may seen complicated, but it was necessary to do it this way to get as much evidence as possible from as few volunteers as possible. The size of the study was too small to be able to place statistical confidence in the results from the four groups separately, although they showed good support for the main finding: average survival was 16.9 months for those on observation only, 13.9 months for chemoradiotherapy, 21.6 months for chemotherapy, and 19.9 months for the combination therapy. Chemoradiotherapy clearly proved harmful, whichever way the results were looked at.

Before too many conclusions are drawn, it must be remembered that this trial examined three specific forms of postoperative treatment, involving the use of fluorouracil and leucovorin, along with radiotherapy in some cases. It really can't provide definitive information on the likely results with other, perhaps newer, chemotherapy drugs. Furthermore, the treatment regimens are tough; side effects can be so intolerable that some patients may decide the likely survival time gained isn't a gamble they want to take.

An editorial in the same edition of the Journal ² reminds us of the strides that have been made in surgery for pancreatic cancer, and the results of studies such as this one that help define optimal postoperative treatment against a background of steady advances in new therapies.

Source

• A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. JP. Neoptolemos, DD. Stocken, H. Freiss,  et al., N Engl J Med, 2004, vol. 350, pp. 1200--1210

Footnotes
1. Gy is an abbreviation for Gray, a measure of dose of irradiation; i.e. the amount of energy transferred to substance being irradiated.
2. Adjuvant therapy for pancreatic cancer - the debate continues. MA. Choti, Editorial. N Engl J Med, 2004, vol. 350, pp. 1249--1251

Related Links
Pancreatic Cancer Action Network
First Step on the Last Journey
Use or Avoid? Advice on Alternative Cancer Treatments
MedlinePlus: Pancreatic Cancer

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