Treatment with Gemcitabine (Gemzar) for Six Months After Complete Resection of Pancreatic Carcinoma Significantly Increases Disease-free Survival and Overall Survival Compared with Observation Alone

Clinical Trial Reports from ASCO

Advances in Noncolorectal Gastrointestinal Cancers

Although gemcitabine-based chemotherapy is standard in advanced pancreatic cancer, the role of adjuvant chemotherapy is still incompletely defined.

CONKO-1 was designed to evaluate the efficacy and toxicity of gemcitabine in patients with pancreatic cancer after complete (R0 or R1) resection. In an oral presentation, Helmut Oettle, MD, PhD, Charité School of Medicine, Berlin, Germany, disclosed the final results of the trial.

After stratification for R0/R1, nodal tumor involvement, and tumor stage, patients were randomized to receive either gemcitabine (1 g/m2 d 1, 8 and 15 every 4 wk) for six months or observation (O) alone. Patients in the observation group received no specific anticancer treatment. The primary study endpoint was disease-free survival (DFS).

Of 368 patients who were randomized, 354 were eligible for intent-to-treat-analysis. As previously reported (ASCO 2005), initial results showed that postoperative gemcitabine is well tolerated and significantly delays the development of recurrent disease after complete resection of pancreatic carcinoma.

At three years, estimated DFS in the gemcitabine and observation groups was 23.5% and 8.5%, respectively. At five years, estimated DFS in these groups was 16.0% and 6.5%, respectively. Subgroup analyses demonstrated significantly increased DFS for gemcitabine in all stratification subgroups.

Gemcitabine also significantly improved median OS. Estimated OS at three years in the gemcitabine and observation groups was 36.5% and 19.5%, respectively. Estimated OS in the two groups at five years was 21.0% and 9.0%, respectively.

In this study, treatment with gemcitabine for six months after complete resection of pancreatic cancer significantly increased DFS and OS, compared with observation alone.

“We have shown that this treatment more than doubles the overall survival five years after treatment,” said Dr. Oettle.

“We can now say that giving this agent after surgery to patients with early-stage disease will improve a patient’s survival,” commented Dr. Nicholas Petrelli of the Helen F. Graham Cancer Center, Wilmington, Delaware, an attendee of the presentation. “We couldn’t say that before.”

Less than 20% of patients with pancreatic cancer are candidates for surgery because the disease is often detected in the late stages. Gemcitabine has been a standard treatment for patients with advanced (and inoperable) pancreatic cancer for a decade. The new findings support use of the drug in the adjuvant setting.

Combination of Gemcitabine (Gemzar), Erlotinib (Tarceva) and Bevacizumab (Avastin) Is Well Tolerated and Shows Modest Activity in Patients with Locally Advanced or Metastatic Pancreatic Cancer

In a poster presentation, Lawrence S. Blaszkowsky, MD, Department of Hematology-Oncology, Massachusetts General Hospital, Boston, reported the results of a phase II study performed to evaluate the safety and efficacy of adding bevacizumab to gemcitabine and erlotinib in patients with advanced or metastatic pancreatic adenocarcinoma.

Thirty patients with locally advanced or metastatic pancreatic cancer who had adequate hepatic, renal, and hematopoietic function and an ECOG performance status of 0-1, were enrolled. Treatment consisted of gemcitabine 1,000 mg/ m2 IV on days 1, 8, and 15; erlotinib 100 mg orally days 1-28; and bevacizumab 10 mg/kg IV days 1 and 15, every 28 days.

Tumor measurements were performed every eight weeks. Patients were assessed for radiologic response (based on RECIST), time to tumor progression (TTP), median OS, 1-year survival, and toxicity. Twenty-eight patients began treatment. Of the 28 treated patients, three had locally advanced disease and 25 had metastatic pancreatic cancer.

Response data were reported for 23 patients. There were five partial responses (22%), four confirmed partial responses (17%), 13 patients with stable disease (57%), and six with progressive disease (26%). Median TTP was 3.5 months. Median OS was 6.8 months.

Grade 3-4 treatment-related toxicities included neutropenia (27%), elevated SGOT (7.7%), elevated SGPT (7.7%), fatigue (11.5%), acneform rash (7.7%), duodenal hemorrhage (3.8%), pulmonary embolism (3.8%), and an arterial event (3.8%).

The investigators concluded that the combination of gemcitabine, erlotinib, and bevacizumab was well tolerated and showed modest activity in patients with locally advanced or metastatic pancreatic cancer. Further investigation is warranted.