RTOG: Gemzar Fails to Show Survival Benefit in Advanced Pancreatic Cancer

TORONTO ? The addition of Gemzar (gemcitabine) to paclitaxel and radiotherapy for locally advanced pancreatic cancer did not significantly improve median survival when compared with just paclitaxel and radiotherapy.

Moreover, the randomized phase-II trial with Gemzar also found that adding an investigational farnesyl transferase inhibitor as maintenance therapy increased toxicities without improving survival.

The data, originally presented at the 2006 Gastrointestinal Cancer Symposium of the American Society of Clinical Oncology, were discussed here at the semi-annual meeting of the Radiation Therapy Oncology Group.

One arm of the randomized RTOG 00-20 phase-II trial treated patients with unresectable, locally advanced pancreatic cancer with weekly Gemzar, Taxol and external radiotherapy. A second trial arm added the farnesyl transferase inhibitor R115777 to that regimen.

Christopher Willett, M.D., a professor and chairman of radiation oncology at Duke in Durham, N.C., said RTOG 00-20's primary objective was to determine median survival rates with these two regimens.

Secondary objectives were to:

• determine the toxicity and loco-regional activity of Taxol, Gemzar,and radiation
• determine the feasibility and tolerability of prolonged administration of R15777
• evaluate whether R15777 can increase progression-free and overall survival after chemotherapy for locally advanced pancreatic cancer
• and finally, to compare the results to historic controls, namely RTOG 98-12 using Taxol and radiotherapy at 50.4 Gy.

The weekly doses of Taxol and Gemzar were 40 mg/m2 and 75 mg/m2 respectively; the R15777 dose was 300 mg taken orally for 21 days every 28 days.

There were 87 analyzable patients in the chemotherapy-radiotherapy arm of RTOG 00-20 and 92 in the chemotherapy-radiotherapy-R115777 arm, for a total of 179 patients.

Median survival for the chemotherapy-radiotherapy and for the chemotherapy-radiotherapy-R115777 arms of RTOG 00-20, were 12 and nine months respectively, not statistically significantly different. Dr. Willett said there was also no statistically significant difference between those two median survivals and the 11.3-month median survival in the historical control trial, RTOG 98-12.

"The curves were basically superimposable," he said.

Dr. Willett suggested that the lack of improvement in the new study's two arms compared with the historical control might have been due to more patients with advanced disease in RTOG 00-20.

One important difference between study arms in RTOG 00-20, however, was in toxicity. Dr. Willett reported a 17% rate of acute toxicity with the addition of the farnesyl transferase inhibitor versus 6% for the chemotherapy-radiotherapy arm.

"We should all note the range of unusual toxicities such as neurologic, muscle and skeletal, concurrent with the addition of the farnesyl transferase inhibitor," Dr. Willett said.

The discussant for this session, Peter Pisters, M.D., a professor of surgical oncology at the University of Texas M.D. Anderson Cancer Center in Houston, said RTOG 00-20 was a success in that it accrued so many patients in a short time.

But he questioned whether the patients in 00-20 really were more advanced than in the historical control, 98-12.

"TN staging is inherently imprecise" in pancreatic cancer, Dr. Pisters said.

He also said nodal status is not accurately assessed by imaging, and that tumor size was not available for patients on 98-12.