Is the Therapeutic Index Better with Gemcitabine-Based Chemoradiation

Ryan Smith, MD
University of Pennsylvania Cancer Center
Last Modified: November 5, 2001

Presenter: Christopher Crane
Affiliation: M.D. Anderson Cancer Center
Type of Session: Scientific

Background

Locally advanced pancreatic cancer is both radioresistant and chemoresistant.

"Traditional" treatment with concurrent 5-FU chemoradiation results in a median survival of 9-12 months

In metastatic/advanced disease, gemcitabine is modestly better than 5-FU

This study was designed to compare the efficacy and toxicity of gemcitabine based chemoradiation with that of 5-FU based chemotherapy (the standard treatment)

Materials and Methods

This is a retrospective look at 114 patients with localized, unresectable (but nonmetastatic) adenocarcinoma of the pancreas that were treated with either gemcitabine or 5-FU based chemoradiation

Unresectability was defined as celiac or SMA involvement or occlusion of the SMV-portal venous confluence

53 pts. in the gemcitabine arm received concurrent XRT (30 Gy in 10 fractions)

61 pts. in the 5-FU arm received concurrent XRT (30 Gy in 10 fractions)

Radiation was delivered to the primary tumor and regional nodes

Groups fairly balanced except: Gemcitabine patients were younger (60 vs 68 yrs), gemcitabine patients had a larger tumor cross sectional area (8.8 vs 5.7 cm2)

Results

Gemcitabine patients developed significantly more severe toxicities during treatment (23% vs. 2%)

OS 11 months (gemcitabine) vs 9 months (5-FU), with 1 yr OS rate 42% vs 28%

Local progression rate 73% (gemcitabine) vs. 61% (5-FU)

5/53 had eventual resection in the gemcitabine group. 4/5 had <1 cm of abutment of the SMA and 1/5 likely had an original component of pancreatitis

Author's Conclusions

Despite selection bias (younger, healthier patients), significantly higher severe toxicity with the gemcitabine group

No statistically significant improvement in 1 yr OS, local progression

5/53 had resection in the gemcitabine group, even though these patients had, on average, larger tumors prior to therapy

Most important factor for the development of toxicity is the amount of mucosa irradiated

Clinical/Scientific Implications
In patients with locally advanced pancreatic cancer, cure is often not feasible. Therefore, different endpoints (palliation, extension of life) are used. Given these facts, excessive morbidity from treatment should be avoided if possible. This study resulted in a 23% rate severe toxicity in the gemcitabine arm plus radiation therapy arm. This was seen without much improvement in OS or local control. Although some patients were able to undergo resection, the patient characteristics or outcomes after surgery were not revealed. Therefore, although the use of gemcitabine is a possible encouraging step forward in pancreatic cancer, it should be used with caution, under close observation, and only on a study protocol.

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