Postoperative Adjuvant Gemcitabine Plus Oxaliplatin (GemOx)Chemotherapy in Patients with Pancreatic Adenocarcinoma: Final Results of a Single Arm Multicenter Phase II Study

Reviewer: Nathan Jones DO
Abramson Cancer Center of the University of Pennsylvania
Last Modified: September 22, 2008

Presenter: Francoise Mornex
Presenter's Affiliation: Centre Hospitalier Lyon Sud, Lyon, France
Type of Session: Scientific

Background

Pancreas cancer treated with surgery alone has produced disappointing results including high rates of positive margins and rapid development of distant metastases
At the time of initiation of this study, adjuvant chemoradiation was widely considered the standard treatment following curative surgery (which has since become a point of controversy, as additional evidence has placed into question the need for radiation post-operatively [ESPAC-1])
Gemcitabine is known to be active in advanced pancreas cancer and is a powerful radiation sensitizer
Gemcitabine and oxaliplatin have been shown to have supra-additive effect in-vitro
This study was derived as an attempt to more adequately treat micrometastatic disease earlier in the treatment course
This is a Phase II study to look at the feasibility and effectiveness of treating completely resected pancreas cancer patients with 6 cycles of Gemcitabine/Oxaliplatin (GemOx) followed by concurrent gemcitabine and radiation (GemRT)

Materials and Methods

Multi-institutional prospective Phase II, single arm study
Post-operative patients were treated with 6 cycles of GemOx followed by a 4-week break, and then received GemRT
GemOx – 1000 mg/m² gemcitabine on day 1, 100 mg/m² oxaliplatin on day 2 q2 weeks x 6 cycles
GemRT – 100 mg/m² gemcitabine weekly concurrent with RT to 50 Gy in 2 Gy daily fractions over 5 weeks
Inclusion criteria </= 8 weeks from surgery, R0 completely resected adenocarcinoma of the pancreas, KPS >70 and CA 19.9 not elevated
CT scans were performed prior to starting both chemotherapy and chemoradiation, and patients who had developed distant disease were excluded
Primary endpoint – 1 year recurrence free survival
Secondary endpoints – 2 year overall survival and toxicity
CTV – pre-operative tumor bed, peripancreatic lymph nodes, and hepatic hilum with 1 cm expansion to PTV

Results

51 patients were enrolled over approximately 2 years
Median age 59.2 years
96% had KPS >/= 80
85% of patients completed all 6 cycles of chemotherapy and 76% completed GemRT
Of patients receiving radiation, 98% completed 50 Gy
1-year recurrence free survival 71%
2-year overall survival 74%
8 of 51 patients developed distant metastases prior to GemRT
Acute Grade 3/4 toxicity
- GemOx – 29% hematologic, 16% gastrointestinal
  - 2 Grade 4 neutropenia
- GemRT – 19% neutropenia, 70% thrombocytopenia
  - 2 Grade 4 (neutropenia and esophagitis)
Late Grade 3/4 toxicity – 2% paresthesia, 2% anemia
44% of tumors were in the pancreatic head
29% were confined to the pancreas with 64% invading duodenum or peripancreatic tissue
No treatment related deaths

Author's Conclusions

Adjuvant GemOx followed by GemRT is both feasible and well tolerated for treatment of completely resected adenocarcinoma of the pancreas
These data are encouraging with regards to both recurrence free and overall survival and warrants further exploration of adjuvant chemotherapy followed by chemoradiation
The presenter suggests that early initiation of chemotherapy prior to initiation of radiation may select out those patient who would develop distant metastases sooner, and thereby be less likely to benefit from local treatment i.e. radiation therapy

Clinical/Scientific Implications

These data demonstrate the tolerability of adjuvant chemotherapy followed by chemoradiation with a gemcitabine containing regimen for completely resected adenocarcinoma of the pancreas
This warrants further investigation in a randomized controlled study to demonstrate improved clinical efficacy of this regimen over either chemotherapy or chemoradiation alone using standard regimens