The addition of high doses of erlotinib to the treatment regimen of bevacizumab and capecitabine with radiotherapy seems to benefit patients with locally advanced pancreatic cancer, according to results of a phase I study presented at the American Association for Cancer Research’s Pancreatic Cancer: Progress and Challenges conference, being held here June 18-21.
“The combination of erlotinib, bevacizumab, capecitabine and radiation was safe, well tolerated and showed promising activity in patients with unresectable, locally advanced pancreatic cancer,” said Christopher H. Crane, M.D., professor, program director and section chief, gastrointestinal section, department of radiation oncology, The University of Texas MD Anderson Cancer Center in Houston.
A total of 17 patients with CT-staged, biopsy-proven, nonmetastatic, unresectable, locally advanced pancreatic cancer were enrolled in the phase I clinical trial from March 2008 to October 2010. A combination treatment regimen of bevacizumab, capecitabine and radiotherapy has been previously shown to be safe. The objective of this study was to determine the safety, tolerability and maximum tolerated dose of a combination of erlotinib, bevacizumab and capecitabine given with concurrent radiation.
Two patients were enrolled at dose levels (DLs) one to four, and nine patients at DL five. Following drug escalation, the patients were reassessed for potential surgical resection of their tumors.
“Of five patients who underwent margin-negative resections, four had tumors that were originally deemed unresectable; four were treated at DLs four or five; three patients had excellent pathological responses at pancreatectomy and are alive at 13, 21 and 22 months respectively with no local or distant failures,” the researchers wrote in the study.
“We were pleasantly surprised by the long median survival duration (23.6 months from diagnosis) and high degree of pathologic response among the five patients that were able to have surgery,” Crane said. “Importantly, there was also a very low toxicity rate. All of the events reported were known effects of the drugs or radiation.”
A total of three patients at DL five developed a grade 3 acute toxicity (two with diarrhea and one with rash). Grade 4 or 5 toxicities were not seen. DL four was selected as the recommended dose.
“This is the third single-arm study using erlotinib concurrently with radiotherapy that has resulted in encouraging median survival duration,” Crane said. “Based on our results, we suggest further studies are warranted using this combination in patients with locally advanced pancreatic cancer.”
Crane has no relevant financial disclosures. The trial was funded by Genentech.
Abstract: Phase I Trial of Radiotherapy with Concurrent Bevacizumab, Erlotinib and Capecitabine for Locally Advanced Pancreatic Cancer (LAPC). Heath D. Skinner, Christopher H. Crane, Sunil Krishnan, Milind M. Javle, Robert A. Wolff, Jason B. Fleming, Marilyn V. Clemons, Mark F. Munsell, Marc E. Delclos, Prajnan Das. University of Texas M. D. Anderson Cancer Center, Houston, TX.
American Association for Cancer Research